Dr Hui Chen is an Associate Professor in the School of Life Sciences. She is the Director of China Programs, Faculty of Science and lecturing in human physiology, pathophysiology, and pharmacology.
Hui completed her medical training and obtained her MD degree in 2002 at Nanjing University, China. She then completed her PhD degree in neuroscience at The University of Melbourne (Apr 2003 - Apr 2006), where she studied brain regulation of appetite and energy metabolism in two mouse models, dietary obesity and cigarette smoking. Immediately after her PhD, she took up a Research Associate position at the University of New South Wales (Apr 2006 - Aug 2008), where she moved into a new area of research, dealing with foetal programming of early onset obesity and metabolic disorders. Hui established two world’s first rodent models of maternal obesity and maternal cigarette smoking. Her research focused on the neural regulation of appetite and brain glucose metabolism. Hui continued the same research area after she joined UTS in 2008, where her research has been extended to study foetal programming of chronic disorders in multiple organ systems while maintaining the primary interest in neuroscience, including brain injury, cognitive dysfunction, type 2 diabetes, chronic kidney disease, asthma, COPD. Her mechanistic studies focus on oxidative stress and mitochondrial integrity, as well as. In 2015, she established world's first mouse model of maternal e-cigarette vaping model, and led the research on neural outcomes in this condition.
Her second research program focuses on drug development for weight loss and treating type 2 diabetes and novel technology for treating type 1 diabetes.
Member of: Australian Neuroscience Society, International Society of Neurochemistry.
Senior editor: Journal of Inflammation
Editorial board member: Scientific Reports
Can supervise: YES
Dr Chen is an expert in animal modeling of human diseases, especially for pre-clinical trials, such as obesity, type 2 diabetes, cognitive dysfunction, neural injury, asthma, COPD, and chronic kidney diseases, as well as drug development for diabetes. Collaborations for pre-clinical trials are welcome.
- foetal programming
- maternal obesity
- maternal tobacco cigarette smoking
- maternal e-cigarette vaping
- maternal air pollution exposure
- neurocognitive dysfunction
- metabolic disorders
- pre-clinical trial
Major techniques used for this work include testing hormone and lipid levels in the blood by biosassays, real-time PCR, western blotting, immunohistochemistry, lipidomics, RNA sequencing.
Subject coordinator for Human Pathophysiology (91239)
Teaching focuses on the physiology and pathophysiology of disorders in Gastrointestinal System, Nutrition Metabolism, Endocrine System, and Body Weight Control in Obesity, as well as drug treatment for diabetes.
Oveisi, S, Mahboobi, M & Chen, H 2020, 'Investigating the criminals exposed to inter-partner violence and child abuse: A case–control study', Social Health and Behavior, vol. 3, no. 1, pp. 10-10.View/Download from: Publisher's site
Xie, Z, Gao, G, Wang, H, Li, E, Yuan, Y, Xu, J, Zhang, Z, Wang, P, Fu, Y, Zeng, H, Song, J, Hölscher, C & Chen, H 2020, 'Dehydroabietic acid alleviates high fat diet-induced insulin resistance and hepatic steatosis through dual activation of PPAR-γ and PPAR-α', Biomedicine and Pharmacotherapy, vol. 127.View/Download from: Publisher's site
© 2020 The Author(s) Dual-PPAR-α/γ agonist has the dual potentials to improve insulin resistance (IR) and hepatic steatosis associated with obesity. This study aimed to investigate whether dehydroabietic acid (DA), a naturally occurred compound, can bind to and activate both PPAR-γ and PPAR-α to ameliorate IR and hepatic steatosis in high-fat diet (HFD)-fed mice. We found that DA formed stable hydrogen bonds with the ligand-binding domains of PPAR-γ and PPAR-α. DA treatment also promoted 3T3-L1 differentiation via PPAR-γ activation, and mitochondrial oxygen consumption in HL7702 cells via PPAR-α activation. In HFD-fed mice, DA treatment alleviated glucose intolerance and IR, and reduced hepatic steatosis, liver injury markers (ALT, AST), and lipid accumulation, and promoted mRNA expression of PPAR-γ and PPAR-α signaling elements involved in IR and lipid metabolism in vivo and in vitro, and inhibited mRNA expression of pro-inflammatory factors. Therefore, DA is a dual-PPAR-α/γ and PPAR-γ partial agonist, which can attenuate IR and hepatic steatosis induced by HFD-consumption in mice.
Chan, YL, Oliver, BG & Chen, H 2020, 'What lessons have we learnt about the impact of maternal cigarette smoking from animal models?', Clinical and Experimental Pharmacology and Physiology, vol. 47, no. 2, pp. 337-344.View/Download from: Publisher's site
Maternal first- or second-hand tobacco smoking during pregnancy is still common albeit that the detrimental effects to the unborn child are well known. Maternal tobacco cigarette smoking can affect multiple organ systems in the offspring, rendering them at increased risk of various conditions throughout life (eg. intrauterine underdevelopment, asthma, substance abuse, diabetes). However, this review will only focus on its impact on the brain and the related molecular changes in the offspring based on evidence from animal studies. Although epidemiological studies have identified the associations between maternal cigarette smoke exposure (SE) and brain disorders, animal models can help identify the underlying mechanisms and test interventions. Human studies have found that maternal SE is closely linked to small brain size and changes in brain structure and associated with a high risk of cognitive defects. Animal models suggest that this may be due to increased brain oxidative stress and inflammation during the neonatal period, leading to increased brain cell apoptosis in adulthood. There is a distinct gender bias of such impacts, where male offspring are more affected than females. Female offspring seem to have developed the adaptation by increasing endogenous antioxidant levels. Indeed, animal studies have shown that using antioxidant supplementation during pregnancy can improve neurological outcomes in male offspring, however, the efficacy in humans is yet to be confirmed. Furthermore, some animal studies suggested nicotine as the key player in intrauterine underdevelopment due to maternal SE, while human clinical trials using nicotine replacement therapy do not support this mechanism. This review will discuss the possible reasons.
Chen, H, Li, G, Allam, VSRR, Wang, B, Chan, YL, Scarfo, C, Ueland, M, Shimmon, R, Fu, S, Foster, P & Oliver, BG 2020, 'Evidence from a mouse model on the dangers of thirdhand electronic cigarette exposure during early life.', ERJ open research, vol. 6, no. 2.View/Download from: Publisher's site
Thirdhand exposure to e-cigarette residue is likely to have harmful effects in children http://bit.ly/38a2umw.
Li, G, Chan, YL, Wang, B, Saad, S, George, J, Oliver, BG & Chen, H 2020, 'E-cigarettes damage the liver and alter nutrient metabolism in pregnant mice and their offspring', ANNALS OF THE NEW YORK ACADEMY OF SCIENCES.View/Download from: Publisher's site
Li, G, Chan, YL, Wang, B, Saad, S, Oliver, BG & Chen, H 2020, 'Replacing smoking with vaping during pregnancy: Impacts on metabolic health in mice', Reproductive Toxicology, vol. 96, pp. 293-299.View/Download from: Publisher's site
© 2020 Elsevier Inc. Smoking is a significant risk factor for the development of metabolic diseases. Due to social pressures to quit smoking, many pregnant women are vaping as an alternative nicotine source. However, the metabolic consequences of replacing tobacco cigarettes with e-cigarettes during pregnancy are unknown. Therefore, in the mothers and their offspring, we investigated the metabolic and hepatic impacts of replacing cigarette smoke with e-vapour during pregnancy. Female BALB/c mice were either air-exposed or cigarette smoke-exposed (SE) from six weeks before pregnancy until lactation. At mating, a subset of the SE mice were instead exposed to e-vapour. Markers of glucose and lipid metabolism were measured in the livers and plasma, from the mothers and their male offspring (13 weeks). In the SE mothers, plasma insulin levels were reduced, leading to downstream increases in hepatic gluconeogenesis and plasma non-esterified fatty acids (NEFA). In the e-vapour replacement mothers, these changes were not as significant. In the SE offspring, there was impaired glucose tolerance, and increased plasma NEFA and liver triglyceride concentrations. E-vapour replacement restored lipid homeostasis but did not improve glucose tolerance. Therefore, in a murine model, low dose e-cigarette replacement during pregnancy is less toxic than cigarette smoke.
Wang, B, Chan, YL, Zhou, S, Saad, S, Chen, H & Oliver, BG 2020, 'Offspring sex affects the susceptibility to maternal smoking-induced lung inflammation and the effect of maternal antioxidant supplementation in mice', JOURNAL OF INFLAMMATION-LONDON, vol. 17, no. 1.View/Download from: Publisher's site
Wang, B, Chen, H, Chan, YL & Oliver, BG 2020, 'Is there an association between the level of ambient air pollution and COVID-19?', AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, vol. 319, no. 3, pp. L416-L421.View/Download from: Publisher's site
Wang, B, Chen, H, Chan, YL, Wang, G & Oliver, BG 2020, 'Why Do Intrauterine Exposure to Air Pollution and Cigarette Smoke Increase the Risk of Asthma?', FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, vol. 8.View/Download from: Publisher's site
Zakarya, R, Sapkota, A, Chan, YL, Shah, J, Saad, S, Bottle, SE, Oliver, BG, Gorrie, CA & Chen, H 2020, 'Nitroxides affect neurological deficits and lesion size induced by a rat model of traumatic brain injury', NITRIC OXIDE-BIOLOGY AND CHEMISTRY, vol. 97, pp. 57-65.View/Download from: Publisher's site
Chen, H, Power, T, Hayes, C, Reyna, J & van Reyk, D 2020, 'Perceptions of Video Scenarios to Learn Human Pathophysiology Among Undergraduate Science Students', JOURNAL OF SCIENCE EDUCATION AND TECHNOLOGY.View/Download from: Publisher's site
Oliver, B, Tonga, K, Darley, D, Rutting, S, Zhang, X, Chen, H & Wang, G 2019, 'COPD treatment choices based on blood eosinophils: are we there yet?', Breathe (Sheffield, England), vol. 15, no. 4, pp. 318-323.View/Download from: Publisher's site
Eosinophils are increasingly being recognised as an important characteristic feature of COPD. Patients with COPD and eosinophilic inflammation tend to respond to steroid therapy; however, many questions remain regarding the optimum measurement. Eosinophilic inflammation may be defined based on various sampling techniques, including eosinophil levels in blood, sputum, bronchoalveolar lavage or biopsy, which leads to inconsistencies in its definition. Blood eosinophils may increase in conjunction with sputum eosinophils during COPD exacerbations and therefore may be a good surrogate marker of airway eosinophilic inflammation. However, the timing of the blood eosinophil measurement, the stability of the eosinophil count and the threshold used in different studies are variable. The use of blood eosinophil count to direct biological therapies in COPD has also had variable outcomes. Eosinophilic inflammation has an important role in COPD management; however, its use as the optimum biomarker still needs further investigation. Key points:Eosinophilia may play a significant role in the pathogenesis of COPD.Eosinophilic inflammation in COPD can be steroid responsive; however, eosinophilic inflammation is variable, and caution needs to be taken with measurements and the thresholds used.The long-term effects of reducing eosinophil levels in COPD is unclear. Educational aims:To explore current knowledge of eosinophils in COPD.To explore the relationship between eosinophilia and corticosteroid use.To understand the limitations of assessing and using eosinophilia in COPD.
Chen, H & Lim, CED 2019, 'The efficacy of using acupuncture in managing polycystic ovarian syndrome', CURRENT OPINION IN OBSTETRICS & GYNECOLOGY, vol. 31, no. 6, pp. 428-432.View/Download from: Publisher's site
Hamedi-Shahraki, S, Eshraghian, M-R, Yekaninejad, M-S, Nikoobakht, M, Rasekhi, A, Chen, H & Pakpour, A 2019, 'Health-related quality of life and medication adherence in elderly patients with epilepsy.', Neurologia i neurochirurgia polska, vol. 53, no. 2, pp. 123-130.View/Download from: Publisher's site
OBJECTIVE:Considering the high prevalence of epilepsy in the elderly and the importance of maximising their quality of life (QoL), this study aimed to investigate the relationship between medication adherence and QoL, and the mediating effects of medication adherence on the association between serum antiepileptic drug (AED) level and seizure severity with QoL in elderly epileptics. METHODS:In a longitudinal study, 766 elderly patients with epilepsy who were prescribed a minimum of one antiepileptic drug were selected by convenience sampling method. A Medication Adherence Report Scale (MARS-5) questionnaire was completed at the baseline. Seizure severity and QoL were assessed after six months using the Liverpool Seizure Severity Scale (LSSS) and the QoL in Epilepsy (QOLIE-31) questionnaires respectively. Serum level of AED was also measured at six-month follow-up. RESULTS:Medication adherence was significantly correlated with both seizure severity (β = -0.33, p < 0.0001) and serum AED level (β = 0.29, p < 0.0001) after adjusting for demographic and clinical characteristics. Neither QoL nor its sub-classes were correlated with seizure severity. In addition, a significant correlation was not observed between serum AED level and QoL. However, medication adherence was significantly correlated with QoL (β = 0.30, p < 0.0001). The mediating effects of medication adherence on the association between serum AED level (Z = 3.39, p < 0.001) and seizure severity (Z = -3.47, p < 0.001) with QoL were supported by the Sobel test. CONCLUSION:This study demonstrates that medication adherence has a beneficial impact on QoL in elderly epileptics. Therefore, adherence to treatment should be monitored to improve their QoL.
Lim, CED, Ng, RWC, Cheng, NCL, Zhang, GS & Chen, H 2019, 'Acupuncture for polycystic ovarian syndrome.', The Cochrane database of systematic reviews, vol. 7, no. 7.View/Download from: Publisher's site
BACKGROUND:Polycystic ovarian syndrome (PCOS) is characterised by the clinical signs of oligo-amenorrhoea, infertility and hirsutism. Conventional treatment of PCOS includes a range of oral pharmacological agents, lifestyle changes and surgical modalities. Beta-endorphin is present in the follicular fluid of both normal and polycystic ovaries. It was demonstrated that the beta-endorphin levels in ovarian follicular fluid of otherwise healthy women who were undergoing ovulation were much higher than the levels measured in plasma. Given that acupuncture impacts on beta-endorphin production, which may affect gonadotropin-releasing hormone (GnRH) secretion, it is postulated that acupuncture may have a role in ovulation induction via increased beta-endorphin production effecting GnRH secretion. This is an update of our previous review published in 2016. OBJECTIVES:To assess the effectiveness and safety of acupuncture treatment for oligo/anovulatory women with polycystic ovarian syndrome (PCOS) for both fertility and symptom control. SEARCH METHODS:We identified relevant studies from databases including the Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CNKI, CBM and VIP. We also searched trial registries and reference lists from relevant papers. CENTRAL, MEDLINE, Embase, PsycINFO, CNKI and VIP searches are current to May 2018. CBM database search is to November 2015. SELECTION CRITERIA:We included randomised controlled trials (RCTs) that studied the efficacy of acupuncture treatment for oligo/anovulatory women with PCOS. We excluded quasi- or pseudo-RCTs. DATA COLLECTION AND ANALYSIS:Two review authors independently selected the studies, extracted data and assessed risk of bias. We calculated risk ratios (RR), mean difference (MD), standardised mean difference (SMD) and 95% confidence intervals (CIs). Primary outcomes were live birth rate, multiple pregnancy rate and ovulation rate, and secondary outcomes were clinical pregna...
Machaalani, R, Thawley, M, Huang, J & Chen, H 2019, 'Effects of prenatal cigarette smoke exposure on BDNF, PACAP, microglia and gliosis expression in the young male mouse brainstem.', Neurotoxicology, vol. 74, pp. 40-46.View/Download from: Publisher's site
Cigarette smoke exposure during pregnancy into infancy affects brain growth and development in both short and long term (into adulthood). Using a mouse model of pre- into post- natal cigarette smoke exposure (SE), we aimed to determine the effects on brain derived neurotrophic factor (BDNF) and its receptor TrkB, neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor PAC1, and astrocyte (GFAP) and microglia (Iba-1) immunohistochemical expression, in seven nuclei of the medulla and the facial (FAC) nucleus of the pons. Male pups of dams exposed to two cigarettes (nicotine <1.2 mg, CO <15 mg) twice daily for six weeks prior to mating, during gestation and lactation (n = 5; SE), were compared to pups exposed to air under the same condition (n = 5; SHAM) at postnatal day 20. Expression changes were only evident for BDNF, TrkB and PAC1 and included decreased BDNF in the hypoglossal (XII) nucleus and nucleus of the solitary tract (NTS), increased TrkB in XII but decreased TrkB in the FAC, and increased PAC1 in 4 nuclei of the medulla including the NTS. These results suggest that the effect of SE on the brainstem are region and marker selective, affecting regions of respiratory control (XII and NTS), and restricted to the BDNF system and PAC1, with no effect on activation states of astrocytes or microglia.
Movahedizadeh, M, Sheikhi, MR, Shahsavari, S & Chen, H 2019, 'The Association between Religious Belief and Drug Adherence Mediated by Religious Coping in Patients with Mental Disorders', Social Health and Behavior, vol. 2, no. 3, pp. 77-82.
Nguyen, LT, Chen, H, Zaky, A, Pollock, C & Saad, S 2019, 'SIRT1 overexpression attenuates offspring metabolic and liver disorders as a result of maternal high-fat feeding.', The Journal of physiology, vol. 597, no. 2, pp. 467-480.View/Download from: Publisher's site
KEY POINTS:Maternal high-fat diet (MHF) consumption led to metabolic and liver disorders in male offspring, which are associated with reduced sirtuin (SIRT)1 expression and activity in the offspring liver SIRT1 overexpression in MHF offspring reduced their body weight and adiposity and normalized lipid metabolic markers in epididymal and retroperitoneal adipose tissues SIRT1 overexpression in MHF offspring improved glucose tolerance, as well as systemic and hepatic insulin sensitivity SIRT1 overexpression ameliorated MHF-induced lipogenesis, oxidative stress and fibrogenesis in the liver of offspring. ABSTRACT:Maternal obesity can increase the risk of metabolic disorders in the offspring. However, the underlying mechanism responsible for this is not clearly understood. Previous evidence implied that sirtuin (SIRT)1, a potent regulator of energy metabolism and stress responses, may play an important role. In the present study, we have shown, in C57BL/6 mice, that maternal high-fat diet (HFD) consumption can induce a pre-diabetic and non-alcoholic fatty liver disease phenotype in the offspring, associated with reduced SIRT1 expression in the hypothalamus, white adipose tissues (WAT) and liver. Importantly, the overexpression of SIRT1 in these offspring significantly attenuated the excessive accumulation of epididymal (Epi) white adipose tissue (WAT) and retroperitoneal (Rp)WAT (P < 0.001), glucose intolerance and insulin resistance (both P < 0.05) at weaning age. These changes were associated with the suppression of peroxisome proliferator-activated receptor gamma (PPAR)γ (P < 0.01), PPARγ-coactivator 1-alpha (P < 0.05) and sterol regulatory element-binding protein-1c in EpiWAT (P < 0.01), whereas there was increased expression of PPARγ in RpWAT (P < 0.05). In the liver, PPARγ mRNA expression, as well as Akt protein expression and activity, were increased (P < 0.05), whereas fatty acid synthase and carbohydrate response element binding protein were downregulated (P...
Nguyen, LT, Mak, CH, Chen, H, Zaky, AA, Wong, MG, Pollock, CA & Saad, S 2019, 'SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet.', Nutrients, vol. 11, no. 1.View/Download from: Publisher's site
Maternal obesity has been associated with kidney disorders in male offspring. Our previous studies have demonstrated that Sirtuin (SIRT)1, an essential regulator of metabolic stress responses, is suppressed in the offspring as the result of maternal high-fat diet (HFD) consumption, which is likely to underpin the adverse metabolic and renal outcomes. To examine if SIRT1 overexpression or activation early in life can protect the offspring kidney, wild-type (WT) and transgenic (Tg) offspring were born to the same diet-induced obese female C57BL/6 mice through breeding with hemizygous SIRT1-transgenic (Tg) male mice and examined for renal pathological changes. In separate experiments, SIRT1 activator SRT1720 (25 mg/kg/2 days i.p) was administrated in WT offspring over 6 weeks of postnatal high-fat diet exposure. The results show that offspring born to obese dams have increased kidney weight, higher levels of renal triglycerides, and increased expression of oxidative stress, inflammatory, and fibrotic markers, as well as increased albuminuria compared to offspring of control dams. Both SIRT1 overexpression and SRT1720 treatment attenuated renal lipid contents and expression of lipogenesis, oxidative stress, and inflammatory markers; however, fibrosis was modestly reduced and albuminuria was not affected. The findings suggest that SIRT1 therapy can ameliorate some pathological mechanisms of kidney programming due to maternal obesity but may not be sufficient to prevent the resulting chronic kidney injury.
Saffari, M & Chen, H 2019, 'Mediating effect of spiritual coping strategies on caregiving burden and mental health in caregivers of Iranian patients with dementia', Social Health and Behavior, vol. 2, no. 4, pp. 117-117.View/Download from: Publisher's site
Saffari, M, Lin, C-Y, Chen, H & Pakpour, AH 2019, 'The role of religious coping and social support on medication adherence and quality of life among the elderly with type 2 diabetes.', Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, vol. 28, no. 8, pp. 2183-2193.View/Download from: Publisher's site
PURPOSE:Type 2 diabetes is a major public health issue particularly in the elderly. Religion may affect the Health Related Quality of Life (HRQoL) in such patients, mediated by factors such as religious coping and social support. This study aimed to investigate the impact of religiosity on medication adherence and HRQoL. METHODS:793 adults (> 65 years old, 45% females) were recruited from 4 diabetes care centers and followed for 1 year. Duke University Religion Index, Spiritual Coping Strategies, Multidimensional Perceived Social Support, Medication Adherence Report Scale, WHOQOL-BREF and Diabetes-specific Quality of Life Questionnaire Module were used for assessment, as well as HbA1c and fasting blood glucose level. Using structural equation modeling, the potential paths were tested between religiosity, medication adherence and HRQoL; social support, religious coping and medication adherence served as the mediators. RESULTS:Religious coping and social support were recognized as the significant mediators between religiosity and medication adherence (CFI = 0.983, TLI = 0.985, and RMSEA = 0.021). The relationships between religiosity and HRQoL were considerably mediated by social support, religious coping and medication adherence and these variables explained 12% and 33% of variances of generic and specific HRQoL, respectively. There was no significant direct effect of religiosity on HRQoL. HbA1c and fasting blood glucose level were successfully loaded on the latent construct of medication adherence (factor loading = 0.51 and 0.44, respectively). CONCLUSIONS:The impact of religiosity on medication adherence and HRQoL occurs through the mediators such as religious coping and social support. Therefore, to improve the adherence to treatment and quality of life, interventions may be designed based on these mediators.
Chan, YL, Wang, B, Chen, H, Ho, KF, Cao, J, Hai, G, Jalaludin, B, Herbert, C, Thomas, PS, Saad, S & Oliver, BGG 2019, 'Pulmonary inflammation induced by low-dose particulate matter exposure in mice.', American journal of physiology. Lung cellular and molecular physiology, vol. 317, no. 3, pp. L424-L430.View/Download from: Publisher's site
Air pollution is a ubiquitous problem and comprises gaseous and particulate matter (PM). Epidemiological studies have clearly shown that exposure to PM is associated with impaired lung function and the development of lung diseases, such as chronic obstructive pulmonary disease and asthma. To understand the mechanisms involved, animal models are often used. However, the majority of such models represent high levels of exposure and are not representative of the exposure levels in less polluted countries, such as Australia. Therefore, in this study, we aimed to determine whether low dose PM10 exposure has any detrimental effect on the lungs. Mice were intranasally exposed to saline or traffic-related PM10 (1μg or 5μg/day) for 3 wk. Bronchoalveolar lavage (BAL) and lung tissue were analyzed. PM10 at 1 μg did not significantly affect inflammatory and mitochondrial markers. At 5 μg, PM10 exposure increased lymphocytes and macrophages in BAL fluid. Increased NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and IL-1β production occurred following PM10 exposure. PM10 (5 μg) exposure reduced mitochondrial antioxidant manganese superoxide (antioxidant defense system) and mitochondrial fusion marker (OPA-1), while it increased fission marker (Drp-1). Autophagy marker light-chain 3 microtubule-associated protein (LC3)-II and phosphorylated-AMPK were reduced, and apoptosis marker (caspase 3) was increased. No significant change of remodeling markers was observed. In conclusion, a subchronic low-level exposure to PM can have an adverse effect on lung health, which should be taken into consideration for the planning of roads and residential buildings.
Li, G, Chan, YL, Sukjamnong, S, Anwer, AG, Vindin, H, Padula, M, Zakarya, R, George, J, Oliver, BG, Saad, S & Chen, H 2019, 'A Mitochondrial Specific Antioxidant Reverses Metabolic Dysfunction and Fatty Liver Induced by Maternal Cigarette Smoke in Mice.', Nutrients, vol. 11, no. 7.View/Download from: Publisher's site
Maternal smoking leads to glucose and lipid metabolic disorders and hepatic damage in the offspring, potentially due to mitochondrial oxidative stress. Mitoquinone mesylate (MitoQ) is a mitochondrial targeted antioxidant with high bioavailability. This study aimed to examine the impact of maternal cigarette smoke exposure (SE) on offspring's metabolic profile and hepatic damage, and whether maternal MitoQ supplementation during gestation can affect these changes. Female Balb/c mice (eight weeks) were either exposed to air or SE for six weeks prior to mating and throughout gestation and lactation. A subset of the SE dams were supplied with MitoQ in the drinking water (500 µmol/L) during gestation and lactation. Intraperitoneal glucose tolerance test was performed in the male offspring at 12 weeks and the livers and plasma were collected at 13 weeks. Maternal SE induced glucose intolerance, hepatic steatosis, mitochondrial oxidative stress and related damage in the adult offspring. Maternal MitoQ supplementation reduced hepatic mitochondrial oxidative stress and improved markers of mitophagy and mitochondrial biogenesis. This may restore hepatic mitochondrial health and was associated with an amelioration of glucose intolerance, hepatic steatosis and pathological changes induced by maternal SE. MitoQ supplementation may potentially prevent metabolic dysfunction and hepatic pathology induced by intrauterine SE.
Stangenberg, S, Nguyen, LT, Chan, YL, Zaky, A, Pollock, CA, Chen, H & Saad, S 2019, 'Maternal L-carnitine supplementation ameliorates renal underdevelopment and epigenetic changes in male mice offspring due to maternal smoking.', Clinical and experimental pharmacology & physiology, vol. 46, no. 2, pp. 183-193.View/Download from: Publisher's site
OBJECTIVES:Epidemiological and animal studies showed that L-carnitine (LC) supplementation can ameliorate oxidative stress-induced tissues damage. We have previously shown that maternal cigarette smoke exposure (SE) can increase renal oxidative stress in newborn offspring with postnatal kidney underdevelopment and renal dysfunction in adulthood, which were normalised by LC administration in the SE dams during pregnancy. Exposure to an adverse intrauterine environment may lead to alteration in the epigenome, a mechanism by which adverse prenatal conditions increase the susceptibility to chronic disease later in life. The current study aimed to determine whether maternal SE induces epigenetic changes in the offspring's kidney are associated with renal underdevelopment, and the protective effect of maternal LC supplementation. METHOD:Female Balb/c mice (7 weeks) were exposed to cigarette smoke (SE) or air (Sham) for 6 weeks prior to mating, during gestation and lactation. A subgroup of the SE dams received LC via drinking water (SE + LC, 1.5 mmol/L) throughout gestation and lactation. Male offspring were studied at postnatal day (P)1, P20, and 13 weeks. RESULTS:Maternal SE altered the expression of renal development markers glial cell line-derived neurotrophic factor and fibroblast growth factor 2, which were associated with increased renal global DNA methylation and DNA methyltransferase 1 mRNA expression at birth. These disorders were reversed by maternal LC administration. CONCLUSION:The effect of maternal SE on renal underdevelopment involves global epigenetic alterations from birth, which can be prevented by maternal LC supplementation.
Brown, P, RELISH Consortium & Zhou, Y 2019, 'Large expert-curated database for benchmarking document similarity in biomedical literature search', Database: the journal of biological databases and curation, vol. 2019, pp. 1-66.View/Download from: Publisher's site
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.
Li, G, Chan, YL, Nguyen, LT, Mak, C, Zaky, A, Anwer, AG, Shi, Y, Nguyen, T, Pollock, CA, Oliver, BG, Saad, S & Chen, H 2019, 'Impact of maternal e-cigarette vapor exposure on renal health in the offspring.', Annals of the New York Academy of Sciences, vol. 1452, no. 1, pp. 65-77.View/Download from: Publisher's site
Maternal smoking during pregnancy is a significant risk factor of renal pathology in the offspring. E-cigarettes are perceived to be a safe option and are increasingly used by pregnant women either continuously during pregnancy or as a replacement for tobacco cigarettes. This study aimed to determine the effects of replacing tobacco cigarettes with e-cigarettes during pregnancy, and continuous e-cigarette use during pregnancy on the offspring's kidneys. Female Balb/c mice were exposed to either air (sham) or tobacco cigarette smoke (SE) for 6 weeks prior to mating, during gestation and lactation. A subset of the "SE group" received e-cigarette vapor (containing nicotine) after mating until pups weaned. Additional female mice were continuously exposed to e-vapor (either with or without nicotine) for 6 weeks prior to mating until pups weaned. Kidneys and urine from the male offspring were assessed at postnatal day 1, day 20 (weaning), and 13 weeks of age (adulthood). E-cigarette replacement was less detrimental to renal development and albuminuria than continuous SE during pregnancy. However, continuous e-vapor exposure during pregnancy increased markers of oxidative stress, inflammation, and fibrosis in the adult offspring, independent of nicotine. E-cigarette use during pregnancy confers future risk to the offspring's kidneys.
Nguyen, T, Li, GE, Chen, H, Cranfield, CG, McGrath, KC & Gorrie, CA 2019, 'Neurological effects in the offspring after switching from tobacco cigarettes to e-cigarettes during pregnancy in a mouse model.', Toxicological Sciences, vol. 172, no. 1, pp. 191-200.View/Download from: Publisher's site
BACKGROUND:Maternal smoking is currently a public health concern and has been associated with a number of complications in the offspring. E-cigarettes are gaining popularity as a 'safer' alternative to tobacco cigarettes during pregnancy, however, there are a limited number of studies to suggest that it is actually 'safe'. STUDY DESIGN:Balb/C female mice were exposed to ambient air (n = 8; Sham), or tobacco cigarette smoke (n = 8; SE) before gestation, during gestation and lactation. A third group was exposed to cigarette smoke before gestation followed by e-cigarette aerosols during gestation and lactation (n = 8; Switch). Male offspring (12-week old, n = 10-14/group) underwent behavioural assessments to investigate short-term memory, anxiety and activity using the novel object recognition (NOR) and elevated plus maze (EPM) tests. Brains were collected at postnatal day (P)1, P20 and Week13 for global DNA methylation, epigenetic gene expression, and neuronal cell counts. RESULTS:The offspring from mothers switching to e-cigarettes exhibited no change in exploration/activity, but showed a decrease in global DNA methylation, Aurora Kinase (Aurk) A and AurkB gene expression and a reduction in neuronal cell numbers in the cornu ammonis 1 region of the dorsal hippocampus compared to the SE group. CONCLUSIONS:Continuous tobacco cigarette smoke exposure during pregnancy resulted in marked neurological deficits in the offspring. Switching to e-cigarettes during pregnancy reduced these neurological deficits compared to cigarette smoke exposure. However, neurological changes were still observed, so we therefore conclude that e-cigarette use during pregnancy is not advised.
Li, G, Saad, S, Oliver, BG & Chen, H 2018, 'Heat or Burn? Impacts of Intrauterine Tobacco Smoke and E-Cigarette Vapor Exposure on the Offspring's Health Outcome.', Toxics, vol. 6, no. 3.View/Download from: Publisher's site
Maternal smoking during pregnancy leads to gestational complications and organ disorders in the offspring. As nicotine replacement therapy is often ineffective for smoking cessation, pregnant women turn to alternatives such as heat-not-burn tobacco and e-cigarettes. Recently, the popularly of e-cigarettes has been increasing especially among the youth and pregnant women, mainly due to the advertisements claiming their safety. This has even led to some clinicians recommending their use during pregnancy. E-cigarettes heat e-liquid to produce an aerosol (e-vapor), delivering flavorings and nicotine to the user. However, e-vapor also contains toxins such as formaldehyde along with heavy metals and carcinogenic nitrosamines. In addition, specific flavoring compounds such as diacetyl can be toxic themselves or decompose into toxic compounds such as benzaldehydes. These compounds can induce toxicity, inflammation and oxidative stress in the mothers and can accumulate in the developing fetus, affecting intrauterine development. Recent animal studies suggest that maternal e-vapor exposure during pregnancy could cause respiratory and neurological disorders in the offspring. This review will examine the available literature to shed light on the current understanding of this problem-to-be from lessons learned in animal models.
Obesity is a high risk for multiple metabolic disorders due to excessive influx of energy, glucose and lipid, often from a western based diet. Low-grade inflammation plays a key role in the progression of such metabolic disorders. The anti-inflammatory property of gold compounds has been used in treating rheumatoid arthritis in the clinic. Previously we found that pure gold nanoparticles (AuNPs, 21 nm) also possess anti-inflammatory effects on the retroperitoneal fat tissue following intraperitoneal injection, by downregulating tumor necrosis factor (TNF) α. However, whether such an effect can change the risk of metabolic disorders in the obese has not been well studied. The study employed C57BL/6 mice fed a pellet high fat diet (HFD, 43% as fat) that were treated daily with AuNPs [low (HFD-LAu) or high (HFD-HAu) dose] via intraperitoneal injection for 9 weeks. In the in vitro study, RAW264.7 macrophages and 3T3-L1 adipocytes were cultured with low and high concentrations of AuNPs alone or together.
The HFD-fed mice showed a significant increase in fat mass, glucose intolerance, dyslipidemia, and liver steatosis. The HFD-LAu group showed an 8% reduction in body weight, ameliorated hyperlipidemia, and normal glucose tolerance; while the HFD-HAu group had a 5% reduction in body weight with significant improvement in their glucose intolerance and hyperlipidemia. The underlying mechanism may be attributed to a reduction in adipose and hepatic local proinflammatory cytokine production, e.g. TNFα. In vitro studies of co-cultured murine RAW264.7 macrophage and 3T3-L1 adipocytes supported this proposed mechanism.
AuNPs demonstrate a promising profile for potential management of obesity related glucose and lipid disorders and are useful as a research tool for the study of biological mechanisms.
Glastras, SJ, Chen, H, Pollock, CA & Saad, S 2018, 'Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring.', Bioscience reports, vol. 38, no. 2.View/Download from: Publisher's site
Obesity, together with insulin resistance, promotes multiple metabolic abnormalities and is strongly associated with an increased risk of chronic disease including type 2 diabetes (T2D), hypertension, cardiovascular disease, non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). The incidence of obesity continues to rise in astronomical proportions throughout the world and affects all the different stages of the lifespan. Importantly, the proportion of women of reproductive age who are overweight or obese is increasing at an alarming rate and has potential ramifications for offspring health and disease risk. Evidence suggests a strong link between the intrauterine environment and disease programming. The current review will describe the importance of the intrauterine environment in the development of metabolic disease, including kidney disease. It will detail the known mechanisms of fetal programming, including the role of epigenetic modulation. The evidence for the role of maternal obesity in the developmental programming of CKD is derived mostly from our rodent models which will be described. The clinical implication of such findings will also be discussed.
Larkin, BP, Glastras, SJ, Chen, H, Pollock, CA & Saad, S 2018, 'DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.', FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 32, no. 10, pp. 5215-5226.View/Download from: Publisher's site
Chronic kidney disease (CKD) is a global epidemic, and its major risk factors include obesity and type 2 diabetes. Obesity not only promotes metabolic dysregulation and the development of diabetic kidney disease but also may independently lead to CKD by a variety of mechanisms, including endocrine and metabolic dysfunction, inflammation, oxidative stress, altered renal hemodynamics, and lipotoxicity. Deleterious renal effects of obesity can also be transmitted from one generation to the next, and it is increasingly recognized that offspring of obese mothers are predisposed to CKD. Epigenetic modifications are changes that regulate gene expression without altering the DNA sequence. Of these, DNA methylation is the most studied. Epigenetic imprints, particularly DNA methylation, are laid down during critical periods of fetal development, and they may provide a mechanism by which maternal-fetal transmission of chronic disease occurs. Our current review explores the evidence for the role of DNA methylation in the development of CKD, diabetic kidney disease, diabetes, and obesity. DNA methylation has been implicated in renal fibrosis-the final pathophysiologic pathway in the development of end-stage kidney disease-which supports the notion that demethylating agents may play a potential therapeutic role in preventing development and progression of CKD.-Larkin, B. P., Glastras, S. J., Chen, H., Pollock, C. A., Saad, S. DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.
Machaalani, R & Chen, H 2018, 'Brain derived neurotrophic factor (BDNF), its tyrosine kinase receptor B (TrkB) and nicotine.', Neurotoxicology, vol. 65, pp. 186-195.View/Download from: Publisher's site
Nicotine is the major neurotoxicant in cigarettes that affects many transmitter systems within the brain as well as other factors, including the growth factors. Brain derived neurotrophic factor (BDNF), is the most abundant growth factor in the brain and plays a critical role in early new neuron differentiation, development and synapsis growth, and the survival of fully developed neurons and synaptic activity. Over the past 3 decades, data has emerged on the effects of nicotine and cigarette smoke exposure on the expression of BDNF and its primary specific receptor tyrosine kinase receptor B (TrkB). This review summarizes data regarding the changes in brain BDNF expression after nicotine or cigarette smoke exposure, and discusses their implications considering BDNF's functional roles.
Nguyen, LT, Chen, H, Mak, C, Zaky, A, Pollock, C & Saad, S 2018, 'SRT1720 attenuates obesity and insulin resistance but not liver damage in the offspring due to maternal and postnatal high-fat diet consumption.', American journal of physiology. Endocrinology and metabolism, vol. 315, no. 2, pp. E196-E203.View/Download from: Publisher's site
Recent studies indicate that sirtuin-1 (SIRT1), an important metabolic sensor and regulator of life span, plays a mechanistic role in maternal obesity-induced programming of metabolic disorders in the offspring. In this study we investigate whether SIRT1 activation in early childhood can mitigate metabolic disorders due to maternal and postnatal high-fat feeding in mice. Male offspring born to chow-fed (MC) or high fat diet-fed dams (MHF) were weaned onto postnatal chow or high-fat diet and treated with SRT1720 (25 mg/kg ip every 2 days) or vehicle control for 6 wk and examined for metabolic disorders. MHF exacerbated offspring body weight and insulin resistance in the offspring exposed to postnatal HFD (OHF). These metabolic changes were associated with reduced hepatic lipid droplet accumulation but increased plasma levels of alanine aminotransferase (ALT), a marker of liver damage. SRT1720 significantly decreased offspring body weight, adiposity, glucose intolerance, and hyperleptinemia due to OHF and reversed hyperinsulinemia and adipocyte hypertrophy due to the additive effects of MHF. Although SRT1720 suppresses liver lipogenesis, inflammation, and oxidative stress markers, it also reduces antioxidants and increased liver collagen deposition in OHF offspring independent of MHF. Hepatic steatosis was attenuated only in MC/OHF offspring in association with elevated plasma ALT levels. The study suggests that postnatal SRT1720 administration can mitigate obesity and insulin resistance in the offspring due to maternal and postnatal HFD exposure. However, the possibility of liver toxicity needs to be further examined.
Chen, H, Chan, YL, Linnane, C, Mao, Y, Anwer, AG, Sapkota, A, Annissa, TF, Herok, G, Vissel, B, Oliver, BG, Saad, S & Gorrie, CA 2018, 'L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury.', Scientific reports, vol. 8, no. 1.View/Download from: Publisher's site
There is a need for pharmaceutical agents that can reduce neuronal loss and improve functional deficits following traumatic brain injury (TBI). Previous research suggests that oxidative stress and mitochondrial dysfunction play a major role in neuronal damage after TBI. Therefore, this study aimed to investigate two drugs known to have antioxidant effects, L-carnitine and exendin-4, in rats with moderate contusive TBI. L-carnitine (1.5 mM in drinking water) or exendin-4 (15 µg/kg/day, ip) were given immediately after the injury for 2 weeks. Neurological function and brain histology were examined (24 h and 6 weeks post injury). The rats with TBI showed slight sensory, motor and memory functional deficits at 24 h, but recovered by 6 weeks. Both treatments improved sensory and motor functions at 24 h, while only exendin-4 improved memory. Both treatments reduced cortical contusion at 24 h and 6 weeks, however neither affected gliosis and inflammatory cell activation. Oxidative stress was alleviated and mitochondrial reactive oxygen species was reduced by both treatments, however only mitochondrial functional marker protein transporter translocase of outer membrane 20 was increased at 24 h post injury. In conclusion, L-carnitine and exendin-4 treatments immediately after TBI can improve neurological functional outcome and tissue integrity by reducing oxidative stress.
Saad, S, Al-Odat, I, Chan, YL, McGrath, KC, Pollock, CA, Oliver, BG & Chen, H 2018, 'Maternal L-carnitine supplementation improves glucose and lipid profiles in female offspring of dams exposed to cigarette smoke.', Clinical and experimental pharmacology & physiology, vol. 45, no. 7, pp. 694-703.View/Download from: Publisher's site
Sex differences in disease susceptibility due to maternal programming have been reported. We previously observed that maternal smoking induced renal disease and neurological changes are restricted to males, while both male and female offspring develop metabolic disorders. We have also found that maternal L-carnitine supplementation during gestation and lactation can significantly improve glucose intolerance and hyperlipidaemia in male offspring. This study aimed to determine whether such beneficial effects can also occur in female offspring. Balb/c female mice were exposed to cigarette smoke (SE) 6 weeks prior to gestation, during gestation and lactation. A subgroup of the SE dams was given L-carnitine (1.5 mmol/L in drinking water) during gestation and lactation. Female offspring were studied at 20 days (weaning) and 13 weeks (adulthood). Maternal smoking increased liver weight (%) and blood glucose levels at 20 days, as well as glucose intolerance and plasma triglycerides levels at adulthood (P < .05). The hepatic lipid metabolic marker adipose triglyceride lipase was downregulated in the SE offspring at 20 days (P < .05). At 13 weeks, the hepatic pro-inflammatory markers IL-1β and TNF-α mRNA expression were upregulated, while the anti-inflammatory marker IL-10 mRNA expression was downregulated in the SE offspring (P < .05). Liver fibrosis was apparent at 20 days and 13 weeks. Maternal L-carnitine supplementation either normalised or suppressed the detrimental effects induced by maternal smoke exposure (P < .05). We conclude that maternal L-carnitine supplementation improves metabolic parameters in the female offspring of SE dams.
Sukjamnong, S, Chan, YL, Zakarya, R, Nguyen, LT, Anwer, AG, Zaky, AA, Santiyanont, R, Oliver, BG, Goldys, E, Pollock, CA, Chen, H & Saad, S 2018, 'MitoQ supplementation prevent long-term impact of maternal smoking on renal development, oxidative stress and mitochondrial density in male mice offspring.', Scientific reports, vol. 8, no. 1.View/Download from: Publisher's site
To investigate the effect of maternal MitoQ treatment on renal disorders caused by maternal cigarette smoke exposure (SE). We have demonstrated that maternal SE during pregnancy increases the risk of developing chronic kidney disease (CKD) in adult offspring. Mitochondrial oxidative damage contributes to the adverse effects of maternal smoking on renal disorders. MitoQ is a mitochondria-targeted antioxidant that has been shown to protect against oxidative damage-related pathologies in many diseases. Female Balb/c mice (8 weeks) were divided into Sham (exposed to air), SE (exposed to cigarette smoke) and SEMQ (exposed to cigarette smoke with MitoQ supplemented from mating) groups. Kidneys from the mothers were collected when the pups weaned and those from the offspring were collected at 13 weeks. Maternal MitoQ supplementation during gestation and lactation significantly reversed the adverse impact of maternal SE on offspring's body weight, kidney mass and renal pathology. MitoQ administration also significantly reversed the impact of SE on the renal cellular mitochondrial density and renal total reactive oxygen species in both the mothers and their offspring in adulthood. Our results suggested that MitoQ supplementation can mitigate the adverse impact of maternal SE on offspring's renal pathology, renal oxidative stress and mitochondrial density in mice offspring.
Chen, H, Ng, JPM, Bishop, DP, Milthorpe, BK & Valenzuela, SM 2018, 'Gold nanoparticles as cell regulators: beneficial effects of gold nanoparticles on the metabolic profile of mice with pre-existing obesity', JOURNAL OF NANOBIOTECHNOLOGY, vol. 16.View/Download from: Publisher's site
Chen, H, Li, G, Chan, YL, Chapman, DG, Sukjamnong, S, Nguyen, T, Annissa, T, McGrath, KC, Sharma, P & Oliver, BG 2018, 'Maternal E-Cigarette Exposure in Mice Alters DNA Methylation and Lung Cytokine Expression in Offspring.', American Journal of Respiratory Cell and Molecular Biology, vol. 58, no. 3, pp. 366-377.View/Download from: Publisher's site
E-cigarette usage is increasing, especially among the young, with both the general population and physicians perceiving them as a safe alternative to tobacco smoking. Worryingly, e-cigarettes are commonly used by pregnant women. As nicotine is known to adversely affect children in utero, we hypothesized that nicotine delivered via e-cigarettes would negatively affect lung development. To test this, we developed a mouse model of maternal e-vapor (nicotine and nicotine-free) exposure and investigated the impact on the growth and lung inflammation in both offspring and mothers. Female Balb/c mice were exposed to e-fluid vapor containing nicotine (18 mg/ml nicotine E-cigarette [E-cig18], equivalent to two cigarettes per treatment, twice daily,) or nicotine free (E-cig0 mg/ml) from 6 weeks before mating until pups weaned. Male offspring were studied at Postnatal Day (P) 1, P20, and at 13 weeks. The mothers were studied when the pups weaned. In the mothers' lungs, e-cigarette exposure with and without nicotine increased the proinflammatory cytokines IL-1β, IL-6, and TNF-α. In adult offspring, TNF-α protein levels were increased in both E-cig18 and E-cig0 groups, whereas IL-1β was suppressed. This was accompanied by global changes in DNA methylation. In this study, we found that e-cigarette exposure during pregnancy adversely affected maternal and offspring lung health. As this occurred with both nicotine-free and nicotine-containing e-vapor, the effects are likely due to by-products of vaporization rather than nicotine.
Chen, H, Li, G, Chan, YL, Nguyen, T, van Reyk, D, Saad, S & Oliver, BG 2018, 'Modulation of neural regulators of energy homeostasis, and of inflammation, in the pups of mice exposed to e-cigarettes.', Neuroscience letters, vol. 684, pp. 61-66.View/Download from: Publisher's site
BACKGROUND:Maternal smoking can lead to perturbations in central metabolic regulators such as neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) signalling components in offspring. With the growing interest in e-cigarettes as a tobacco replacement, this short report assessed central metabolic regulation in offspring of mouse dams exposed to e-cigarettes. We examined the impact of continuous use of e-cigarettes, and e-cigarette replacement of tobacco cigarettes during pregnancy. Supplementation of an antioxidant l-carnitine was also co-used with tobacco cigarette in the mother to determine whether the impact of maternal tobacco smoking was oxidative stress driven. METHODS:Balb/c mice were exposed to either nicotine-containing (E-cig18) or nicotine-free (E-cig0) e-cigarette aerosols or tobacco smoke (SE) prior to mating and until their pups were weaned. After mating, two SE sub-groups were changed to E-cig18 exposure (Replacement), or supplementation l-carnitine while SE was continued. Male offspring were studied at weaning age. RESULTS:The offspring of E-cig0 dams were the heaviest with the most body fat. Replacing SE with E-cig18 during pregnancy resulted in offspring with significantly less body fat. E-cig0 offspring had significantly increased mRNA expression of brain NPY and iNOS. Maternal SE upregulated mRNA expression of NPY, NPY Y1 receptor, POMC downstream components, and iNOS expression, which were normalised in Replacement offspring, but only partially normalised with maternal L-carnitine supplementation during gestation and lactation. CONCLUSIONS:Maternal exposure to either tobacco and nicotine-free e-cigarettes lead to disturbances in the level of central homeostatic control markers in offspring, suggesting that maternal exposure to e-cigarettes is not without risks.
Nguyen, T, Li, GE, Chen, H, Cranfield, CG, McGrath, KC & Gorrie, CA 2018, 'Maternal E-Cigarette Exposure Results in Cognitive and Epigenetic Alterations in Offspring in a Mouse Model.', Chemical research in toxicology, vol. 31, no. 7, pp. 601-611.View/Download from: Publisher's site
Electronic cigarette (e-cigarette) use is on the rise worldwide and is particularly attractive to young people and as a smoking substitute by pregnant woman. There is a perception in pregnant women and women of child-bearing age that the use of e-cigarettes (vaping) is safer than smoking tobacco cigarettes during pregnancy. However, there is little evidence to support this perception. Here, we examined the offspring from mouse dams that had been exposed during and after pregnancy to ambient air (sham) ( n = 8), e-cigarette aerosols with nicotine ( n = 8), or e-cigarette aerosols without nicotine ( n = 8). Offspring underwent cognitive testing at 12 weeks of age and epigenetic testing of brain tissues at 1 day, 20 days, and 13 weeks after birth. The findings showed deficits in short-term memory, reduced anxiety, and hyperactivity in offspring following maternal e-cigarette exposure using the novel object recognition and elevated plus maze tests. In addition, global DNA methylation was increased in the brains of offspring soon after birth. Using a quantitative-PCR array specific to chromatin modification enzymes on genomic DNA and histones,13 key genes were identified to be significantly altered in the offspring brains from the e-cigarette groups compared to the nonexposed groups. The changes to genes Aurka, Aurkb, Aurkc, Kdm5c, Kdm6b, Dnmt3a, Dnmt3b, and Atf2, all associated with modulating neurological activity, were validated using RT-qPCR. In conclusion, in a mouse model, maternal exposure to e-cigarette aerosols resulted in both cognitive and epigenetic changes in offspring. This suggests that the use of e-cigarettes during pregnancy may have hitherto undetected neurological consequences on newborns.
Capistrano, SJ, van Reyk, D, Chen, H & Oliver, BG 2017, 'Evidence of Biomass Smoke Exposure as a Causative Factor for the Development of COPD.', Toxics, vol. 5, no. 4, pp. 1-16.View/Download from: Publisher's site
Chronic obstructive pulmonary disease (COPD) is a progressive disease of the lungs characterised by chronic inflammation, obstruction of airways, and destruction of the parenchyma (emphysema). These changes gradually impair lung function and prevent normal breathing. In 2002, COPD was the fifth leading cause of death, and is estimated by the World Health Organisation (WHO) to become the third by 2020. Cigarette smokers are thought to be the most at risk of developing COPD. However, recent studies have shown that people with life-long exposure to biomass smoke are also at high risk of developing COPD. Most common in developing countries, biomass fuels such as wood and coal are used for cooking and heating indoors on a daily basis. Women and children have the highest amounts of exposures and are therefore more likely to develop the disease. Despite epidemiological studies providing evidence of the causative relationship between biomass smoke and COPD, there are still limited mechanistic studies on how biomass smoke causes, and contributes to the progression of COPD. This review will focus upon why biomass fuels are used, and their relationship to COPD. It will also suggest methodological approaches to model biomass exposure in vitro and in vivo.
Glastras, SJ, Chen, H, Tsang, M, Teh, R, McGrath, RT, Zaky, A, Chen, J, Wong, MG, Pollock, CA & Saad, S 2017, 'The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet.', PLoS ONE, vol. 12, no. 2, pp. 1-17.View/Download from: Publisher's site
AIMS/HYPOTHESIS: Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease. METHODS: Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32. RESULTS: HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity. CONCLUSION: Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity.
Nguyen, LT, Chen, H, Pollock, C & Saad, S 2017, 'SIRT1 reduction is associated with sex-specific dysregulation of renal lipid metabolism and stress responses in offspring by maternal high-fat diet.', Scientific Reports, vol. 7, no. 1, pp. 1-13.View/Download from: Publisher's site
Rodent models of maternal obesity have been associated with kidney damage and dysfunction in offspring. However, the underlying mechanisms are yet to be elucidated. In this study, female rats were fed a high-fat diet (HFD) for 6 weeks prior to mating, throughout gestation and lactation; both male and female offspring were examined at weaning. Our results demonstrate that renal lipid deposition was increased in male offspring only, which is associated with reduced protein expression of Sirtuin (SIRT) 1, an essential regulator of lipid metabolism and stress response. Other components in its signalling network including phosphorylated 5'-AMP-activated protein kinase (pAMPKα), Forkhead box FOXO3a and Peroxisome proliferator-activated receptor (PPAR)γ coactivator 1-alpha (PGC-1α) were also downregulated. By contrast, in female offspring, renal fat/lipid distribution was unchanged in coupling with normal SIRT1 regulation. Specific autophagy and antioxidant markers were suppressed in both sexes. On the other hand, fibronectin and Collagen type IV protein expression was significantly higher in the offspring born HFD-fed dams, particularly in the males. Collectively, these findings suggest that maternal HFD consumption can induce sex-specific changes in offspring kidney lipid metabolism and stress responses at early ages, which may underpin the risk of kidney diseases later in life.
Rahmati-Najarkolaci, F, Pakpour, AH, Saffari, M, Hosseini, MS, Hajizadeh, F, Chen, H & Yekaninejad, MS 2017, 'Determinants of Lifestyle Behavior in Iranian Adults with Prediabetes: Applying the Theory of Planned Behavior', ARCHIVES OF IRANIAN MEDICINE, vol. 20, no. 4, pp. 198-204.
Saffari, M, Pakpour, AH & Chen, H 2017, 'Factors influencing exclusive breastfeeding among Iranian mothers: A longitudinal population-based study.', Health Promotion Perspectives, vol. 7, no. 1, pp. 34-41.View/Download from: Publisher's site
Background: Exclusive breastfeeding (EBF) contributes to the health and survival of the newborns. Many factors influence the EBF behavior. This study aimed to identify the determinant factors in order to improve the practice of EBF among Iranian mothers. Methods: A longitudinal study was carried out in 1445 mothers with newborns in Qazvin city, Iran (September 2015-March 2016). Demographic variables as well as the constructs of theory of planned behavior (TBP) were measured by questionnaires. Bivariate analysis using Pearson and Spearman correlation tests with analysis of variance were used to investigate the associations among the variables. Both hierarchal multiple regression and logistic regression were applied to identify potential determinative factors for the EBF. Results: Nearly, 80% (CI: 77.97-82.63%) of the participants had the intention of EBF. All TPB constructs, moral norms, and self-identity were significantly correlated with each other (r: 0.09- 0.40, P < 0.01). Some demographic variables such as age, income, employment and primiparity were also correlated with the EBF (r: 0.11-0.15, P < 0.05). The constructs of the TPB were able to predict the EBF behavior, which account for 49% of the variance in the predicting factors (df = 8, F = 7.70). The self-identity and moral norms accounted for an additional 15% of the variance (df = 10, F = 3.16). Younger mothers with lower socio-economic status were at higher risk of EBF cessation. The intention has a greater impact on the initiation of EBF than perceived behavioral control (PBC) but not for the maintenance of EBF (OR, 2.88 [CI: 2.38-3.48] & 1.13 [CI:1.03- 1.23] vs. OR, 1.27 [CI:1.15-1.39] & 2.66 [CI: 2.02-3.49]). Conclusion: The interventions to promote knowledge, attitude and behavioral control towards the EBF should be considered especially in the young mothers with low socio-economic status.
Chan, YL, Saad, S, Al-Odat, I, Oliver, BG, Pollock, C, Jones, NM & Chen, H 2017, 'Maternal L-Carnitine Supplementation Improves Brain Health in Offspring from Cigarette Smoke Exposed Mothers.', Frontiers in Molecular Neuroscience, vol. 10, pp. 1-15.View/Download from: Publisher's site
Maternal cigarette smoke exposure (SE) causes detrimental changes associated with the development of chronic neurological diseases in the offspring as a result of oxidative mitochondrial damage. Maternal L-Carnitine administration has been shown to reduce renal oxidative stress in SE offspring, but its effect in the brain is unknown. Here, we investigated the effects of maternal L-Carnitine supplementation on brain markers of oxidative stress, autophagy, mitophagy and mitochondrial energy producing oxidative phosphorylation (OXPHOS) complexes in SE offspring. Female Balb/c mice (8 weeks) were exposed to cigarette smoke prior to mating, during gestation and lactation with or without L-Carnitine supplementation (1.5 mM in drinking water). In 1 day old male SE offspring, brain mitochondrial damage was suggested by increased mitochondrial fusion and reduced autophagosome markers; whereas at 13 weeks, enhanced brain cell damage was suggested by reduced fission and autophagosome markers, as well as increased apoptosis and DNA fragmentation markers, which were partially reversed by maternal L-Carnitine supplementation. In female SE offspring, enhanced mitochondrial regeneration was suggested by decreased fission and increased fusion markers at day 1. At 13 weeks, there was an increase in brain energy demand, oxidative stress and mitochondrial turnover, reflected by the protein changes of OXPHOS complex, fission and autophagosome markers, as well as the endogenous antioxidant, which were also partially normalized by maternal L-Carnitine supplementation. However, markers of apoptosis and DNA fragmentation were not significantly changed. Thus L-Carnitine supplementation may benefit the brain health of the offspring from smoking mothers.
Chan, YL, Saad, S, Machaalani, R, Oliver, BG, Vissel, B, Pollock, C, Jones, NM & Chen, H 2017, 'Maternal Cigarette Smoke Exposure Worsens Neurological Outcomes in Adolescent Offspring with Hypoxic-Ischemic Injury.', Frontiers in Molecular Neuroscience, vol. 10, pp. 1-17.View/Download from: Publisher's site
Hypoxic-ischemic (HI) encephalopathy occurs in approximately 6 per 1000 term newborns leading to devastating neurological consequences, such as cerebral palsy and seizures. Maternal smoking is one of the prominent risk factors contributing to HI injury. Mitochondrial integrity plays a critical role in neural injury and repair during HI. We previously showed that maternal cigarette smoke exposure (SE) can reduce brain mitochondrial fission and autophagosome markers in male offspring. This was accompanied by increased brain cell apoptosis (active caspase-3) and DNA fragmentation (TUNEL staining). Here, we aimed to investigate whether maternal SE leads to more severe neurological damage after HI brain injury in male offspring. Female BALB/c mice (8 weeks) were exposed to cigarette smoke prior to mating, during gestation, and lactation. At postnatal day 10, half of the pups from each litter underwent left carotid artery occlusion, followed by exposure to 8% oxygen (92% nitrogen). At postnatal day 40-44, maternal SE reduced grip strength in grip traction and foot fault tests, which were also reduced by HI injury to similar levels regardless of the maternal group. Limb coordination was impaired by maternal SE which was not worsened by HI injury. Maternal SE increased anxiety level in the offspring, which was normalized by HI injury. Apoptosis markers were increased in different brain regions by maternal SE, with the cortex having further increased TUNEL by HI injury, along with increased markers of inflammation and mitophagy. We conclude that maternal SE can worsen HI-induced cellular damage in male offspring well into adolescence.
Sukjamnong, S, Chan, YL, Zakarya, R, Saad, S, Sharma, P, Santiyanont, R, Chen, H & Oliver, BG 2017, 'Effect of long-term maternal smoking on the offspring's lung health.', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 313, no. 2, pp. L416-L423.View/Download from: Publisher's site
Maternal smoking during pregnancy contributes to long-term health problems in offspring, especially respiratory disorders that can manifest in either childhood or adulthood. Receptors for advanced glycation end products (RAGE) are multiligand receptors abundantly localized in the lung, capable of responding to by-products of reactive oxygen species and proinflammatory responses. RAGE signaling is a key regulator of inflammation in cigarette smoking-related pulmonary diseases. However, the impact of maternal cigarette smoke exposure on lung RAGE signaling in the offspring is unclear. This study aims to investigate the effect of maternal cigarette smoke exposure (SE), as well as mitochondria-targeted antioxidant [mitoquinone mesylate (MitoQ)] treatment, during pregnancy on the RAGE-mediated signaling pathway in the lung of male offspring. Female Balb/c mice (8 wk) were divided into a sham group (exposed to air), an SE group (exposed to cigarette smoke), and an SE + MQ group (exposed to cigarette smoke with MitoQ supplement from mating). The lungs from male offspring were collected at 13 wk. RAGE and its downstream signaling, including nuclear factor-κB and mitogen-activated protein kinase family consisting of extracellular signal-regulated kinase 1, ERK2, c-JUN NH2-terminal kinase (JNK), and phosphorylated JNK, in the lung were significantly increased in the SE offspring. Mitochondrial antioxidant manganese superoxide dismutase was reduced, whereas IL-1β and oxidative stress response nuclear factor (erythroid-derived 2)-like 2 were significantly increased in the SE offspring. Maternal MitoQ treatment normalized RAGE, IL-1β, and Nrf-2 levels in the SE + MQ offspring. Maternal SE increased RAGE and its signaling elements associated with increased oxidative stress and inflammatory cytokines in offspring lungs, whereas maternal MitoQ treatment can partially normalize these changes.
Nguyen, LT, Saad, S, Tan, Y, Pollock, C & Chen, H 2017, 'Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus.', Journal of Molecular Endocrinology, vol. 59, no. 1, pp. 81-92.View/Download from: Publisher's site
Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity.
Capistrano, SJ, Zakarya, R, Chen, H & Oliver, BG 2016, 'Biomass Smoke Exposure Enhances Rhinovirus-Induced Inflammation in Primary Lung Fibroblasts', INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 17, no. 9.View/Download from: Publisher's site
Bertrand, PP, Polglaze, KE, Chen, H, Sandow, SL, Walduck, A, Jenkins, TA, Bertrand, RL, Lomax, AE & Liu, L 2016, 'Excitability and Synaptic Transmission in the Enteric Nervous System: Does Diet Play a Role?', ENTERIC NERVOUS SYSTEM: 30 YEARS LATER, vol. 891, pp. 201-211.View/Download from: Publisher's site
Glastras, SJ, Chen, H, McGrath, RT, Zaky, AA, Gill, AJ, Pollock, CA & Saad, S 2016, 'Effect of GLP-1 Receptor Activation on Offspring Kidney Health in a Rat Model of Maternal Obesity', SCIENTIFIC REPORTS, vol. 6.View/Download from: Publisher's site
Glastras, SJ, Chen, H, Teh, R, McGrath, RT, Chen, J, Pollock, CA, Wong, MG & Saad, S 2016, 'Mouse Models of Diabetes, Obesity and Related Kidney Disease.', PLoS ONE, vol. 11, no. 8, pp. 1-15.View/Download from: Publisher's site
Multiple rodent models have been used to study diabetic kidney disease (DKD). The purpose of the present study was to compare models of diabetes and obesity-induced metabolic syndrome and determine differences in renal outcomes. C57BL/6 male mice were fed either normal chow or high fat diet (HFD). At postnatal week 8, chow-fed mice were randomly assigned to low-dose streptozotocin (STZ, 55 mg/kg/day, five consecutive days) or vehicle control, whereas HFD-fed mice were given either one high-dose of STZ (100 mg/kg) or vehicle control. Intraperitoneal glucose tolerance tests were performed at Week 14, 20 and 30. Urinary albumin to creatinine ratio (ACR) and serum creatinine were measured, and renal structure was assessed using Periodic Acid Schiff (PAS) staining at Week 32. Results showed that chow-fed mice exposed to five doses of STZ resembled type 1 diabetes mellitus with a lean phenotype, hyperglycaemia, microalbuminuria and increased serum creatinine levels. Their kidneys demonstrated moderate tubular injury with evidence of tubular dilatation and glycogenated nuclear inclusion bodies. HFD-fed mice resembled metabolic syndrome as they were obese with dyslipidaemia, insulin resistance, and significantly impaired glucose tolerance. One dose STZ, in addition to HFD, did not worsen metabolic features (including fasting glucose, non esterified fatty acid, and triglyceride levels). There were significant increases in urinary ACR and serum creatinine levels, and renal structural changes were predominantly related to interstitial vacuolation and tubular dilatation in HFD-fed mice.
Glastras, SJ, Tsang, M, Teh, R, Chen, H, McGrath, RT, Zaky, AA, Pollock, CA & Saad, S 2016, 'Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring', SCIENTIFIC REPORTS, vol. 6.View/Download from: Publisher's site
Lin, C-Y, Chen, H & Pakpour, AH 2016, 'Correlation between adherence to antiepileptic drugs and quality of life in patients with epilepsy: A longitudinal study', EPILEPSY & BEHAVIOR, vol. 63, pp. 103-108.View/Download from: Publisher's site
Nguyen, LT, Chen, H, Pollock, CA & Saad, S 2016, 'Sirtuins-mediators of maternal obesity-induced complications in offspring?', FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 30, no. 4, pp. 1383-1390.View/Download from: Publisher's site
Obesity is a complex metabolic disease, attributed to diverse and interactive genetic and environmental factors. The associated health consequences of obesity are pleiotropic, with individuals being more susceptible to chronic diseases such as type 2 diabetes mellitus, hypertension, and lipotoxicity-related chronic diseases. The contribution of maternal obesity to the offspring's predisposition to both obesity and its complications is increasingly recognized. Understanding the mechanisms underlying these "transmissible" effects is critical to develop therapeutic interventions to reduce the risk for "programmed" obesity. Sirtuins (SIRTs), particularly SIRT1 and SIRT3, are NAD(+)-dependent deacetylases that regulate metabolic balance and stress responses in both central and peripheral tissues, of which dysregulation is a well-established mediator for the development and effects of obesity. Nevertheless, their implication in the transmissible effects of maternal obesity across generations remains largely elusive. In this review, we examine multiple pathways and systems that are likely to mediate such effects, with particular emphasis on the role of SIRTs.-Nguyen, L. T., Chen, H., Pollock, C. A., Saad, S. Sirtuins-mediators of maternal obesity-induced complications in offspring?
Chan, YL, Saad, S, Al-Odat, I, Zaky, AA, Oliver, B, Pollock, C, Li, W, Jones, NM & Chen, H 2016, 'Impact of maternal cigarette smoke exposure on brain and kidney health outcomes in female offspring.', Clinical and experimental pharmacology & physiology, vol. 43, pp. 1168-1176.View/Download from: Publisher's site
Increased oxidative stress in the brain can lead to increased sympathetic tone that may further induce kidney dysfunction. Previously we have shown that maternal cigarette smoke exposure (SE) leads to significantly increased oxidative stress and inflammation in both brain and kidney, as well as reduced brain and kidney mitochondrial activity. This is closely associated with significant kidney underdevelopment and abnormal function in adulthood in the male offspring. This study aimed to investigate the impact of maternal SE on brain and kidney health in the female offspring. In this study, the mouse dams were exposed to 2 cigarettes, twice daily for 6 weeks prior to gestation, during pregnancy and lactation. Brains and kidneys from the female offspring were collected at 20 days (P20) and 13 weeks (W13) and were subject to further analysis. We found that mRNA expression of brain inflammatory markers interleukin-1 receptor and Toll-like receptor 4 were significantly increased in the SE offspring at both P20 and W13. Their brain mitochondrial activity markers were however increased at W13 with increased antioxidant activity. Kidney development and function in the female SE offspring were not different from the control offspring. We concluded that although brain inflammatory markers were upregulated in the SE female offspring, they were protected from some of the indicators of brain oxidative stress, such as endogenous antioxidant and mitochondrial dysfunction, as well as abnormal kidney development and function in adulthood. This article is protected by copyright. All rights reserved.
Chan, YL, Saad, S, Pollock, C, Oliver, B, Al-Odat, I, Zaky, AA, Jones, N & Chen, H 2016, 'Impact of maternal cigarette smoke exposure on brain inflammation and oxidative stress in male mice offspring', SCIENTIFIC REPORTS, vol. 6.View/Download from: Publisher's site
Chen, H, Chan, YL, Nguyen, LT, Mao, Y, de Rosa, A, Beh, IT, Chee, C, Oliver, B, Herok, G, Saad, S & Gorrie, C 2016, 'Moderate traumatic brain injury is linked to acute behaviour deficits and long term mitochondrial alterations', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, vol. 43, no. 11, pp. 1107-1114.View/Download from: Publisher's site
Vivekanandarajah, A, Chan, YL, Chen, H & Machaalani, R 2016, 'Prenatal cigarette smoke exposure effects on apoptotic and nicotinic acetylcholine receptor expression in the infant mouse brainstem.', NeuroToxicology, vol. 53, pp. 53-63.View/Download from: Publisher's site
Infants exposed to cigarette smoked during pregnancy into infancy have increased respiratory and cardiac abnormalities. Nicotine, the major neurotoxic component of cigarette smoke, induces its actions by binding to nicotinic acetylcholine receptors (nAChR), with one downstream effect being increased apoptosis. Using a pre- into post- natal cigarette smoke exposure mouse model (SE), we studied the immunohistochemical expression of nAChR subunits α2, α3, α4, α5, α7, α9, β1 and β2 and two markers of apoptosis, active caspase-3 and TUNEL, in seven nuclei of the medulla and facial nucleus of the pons in male mice. Pups of dams exposed to two cigarettes (nicotine ≤1.2mg, CO ≤15mg) twice daily for six weeks prior to mating, during gestation and lactation (n=5; SE), were compared to pups exposed to air under the same condition (n=5; SHAM) at P20. Results showed that the hypoglossal nucleus had increased α3, α4, α7, α9, Casp-3 and TUNEL, dorsal motor nucleus of the vagus had increased α3, α5, α7, β1 and Casp-3, nucleus of the solitary tract had increased α3 but decreased α4, α5, β1 and apoptosis, cuneate nucleus had increased α3, β2 and Casp- 3, but decreased α5, nucleus of the spinal trigeminal tract had increased α3, α7, β1, lateral reticular nucleus had decreased β1, inferior olivary nucleus had increased β1 but decreased apoptosis, and the facial had increased α2, α3 and α7. This is the first study to demonstrate that nAChR subunits are affected following pre- into post-natal SE and that they simultaneously coincided with changes in apoptotic expression.
Chen, H, Kelly, M, Hayes, C, van Reyk, D & Herok, G 2016, 'The use of simulation as a novel experiential learning module in undergraduate science pathophysiology education', ADVANCES IN PHYSIOLOGY EDUCATION, vol. 40, no. 3, pp. 335-341.View/Download from: Publisher's site
Glastras, SJ, Wong, MG, Chen, H, Zhang, J, Zaky, A, Pollock, CA & Saad, S 2015, 'FXR expression is associated with dysregulated glucose and lipid levels in the offspring kidney induced by maternal obesity', NUTRITION & METABOLISM, vol. 12.View/Download from: Publisher's site
Saffari, M, Zeidi, IM, Fridlund, B, Chen, H & Pakpour, AH 2015, 'A Persian Adaptation of Medication Adherence Self-Efficacy Scale (MASES) in Hypertensive Patients: Psychometric Properties and Factor Structure', High Blood Pressure & Cardiovascular Prevention, vol. 22, no. 3, pp. 247-255.View/Download from: Publisher's site
Stangenberg, S, Chen, H, Wong, MG, Pollock, CA & Saad, S 2015, 'Fetal programming of chronic kidney disease: the role of maternal smoking, mitochondrial dysfunction, and epigenetic modfification', AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, vol. 308, no. 11, pp. F1189-F1196.View/Download from: Publisher's site
Stangenberg, S, Nguyen, LT, Chen, H, Al-Odat, I, Killingsworth, MC, Gosnell, ME, Anwer, AG, Goldys, EM, Pollock, CA & Saad, S 2015, 'Oxidative stress, mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking', INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, vol. 64, pp. 81-90.View/Download from: Publisher's site
Zabeau, L, Jensen, CJ, Seeuws, S, Venken, K, Verhee, A, Catteeuw, D, van Loo, G, Chen, H, Walder, K, Hollis, J, Foote, S, Morris, MJ, Van der Heyden, J, Peelman, F, Oldfield, BJ, Rubio, JP, Elewaut, D & Tavernier, J 2015, 'Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level', Cellular and Molecular Life Sciences, vol. 72, no. 3, pp. 629-644.View/Download from: Publisher's site
Chan, YL, Saad, S, Simar, D, Oliver, B, McGrath, K, Reyk, DV, Bertrand, PP, Gorrie, C, Pollock, C & Chen, H 2015, 'Short term exendin-4 treatment reduces markers of metabolic disorders in female offspring of obese rat dams', International Journal of Developmental Neuroscience, vol. 46, pp. 67-75.View/Download from: Publisher's site
Maternal obesity imposes significant health risks in the offspring including diabetes and dyslipidemia. We previously showed that the hypoglycaemic agent exendin-4 (Ex-4) administered from weaning can reverse the maternal impact of 'transmitted disorders' in such offspring. However daily injection for six-weeks was required and the beneficial effect may lapse upon drug withdrawal. This study aimed to investigate whether short term Ex-4 treatment during suckling period in a rodent model can reverse transmitted metabolic disorders due to maternal obesity.
Maternal obesity was induced in female Sprague Dawley rats by high-fat diet feeding for 6 weeks, throughout gestation and lactation. Female offspring were treated with Ex-4 (5 μg/kg/day) between postnatal day (P) 4 and 14. Female offspring were harvested at weaning (P20). Lipid and glucose metabolic markers were measured in the liver and fat. Appetite regulators were measured in the plasma and hypothalamus.
Maternal obesity significantly increased body weight, fat mass, and liver weight in the offspring. There was an associated inhibition of peroxisomal proliferator activated receptor gamma coactivator 1α (PGC1α), increased fatty acid synthase (FASN) expression in the liver, and reduced adipocyte triglyceride lipase (ATGL) expression. It also increased the plasma gut hormone ghrelin and reduced glucagon-like peptide-1. Ex-4 treatment partially reversed the maternal impact on adiposity and impaired lipid metabolism in the offspring, with increased liver PGC1α and inhibition of FASN mRNA expression. Ex-4 treatment also increased the expression of a novel fat depletion gene a2-zinc-glycoprotein 1 in the fat tissue.
Short term Ex-4 treatment during the suckling period significantly improved the metabolic profile in the offspring from the obese mothers at weaning. Long-term studies are needed to follow such offspring to adulthood to examine the sustained effects of Ex-4 in p...
Nguyen, LT, Stangenberg, S, Chen, H, Al-Odat, I, Chan, YL, Gosnell, ME, Anwer, AG, Goldys, EM, Pollock, CA & Saad, S 2015, 'L-Carnitine reverses maternal cigarette smoke exposure-induced renal oxidative stress and mitochondrial dysfunction in mouse offspring.', American journal of physiology. Renal physiology, vol. 308, no. 7, pp. F689-F696.View/Download from: Publisher's site
Maternal smoking is associated with metabolic disorders, renal underdevelopment, and a predisposition to chronic kidney disease in offspring, yet the underlying mechanisms are unclear. By exposing female Balb/c mice to cigarette smoke for 6 wk premating and during gestation and lactation, we showed that maternal smoke exposure induced glucose intolerance, renal underdevelopment, inflammation, and albuminuria in male offspring. This was associated with increased renal oxidative stress and mitochondrial dysfunction at birth and in adulthood. Importantly, we demonstrated that dietary supplementation of l-carnitine, an amino acid shown to increase antioxidant defenses and mitochondrial function in numerous diseases, in smoke-exposed mothers during pregnancy and lactation significantly reversed the detrimental maternal impacts on kidney pathology in these male offspring. It increased SOD2 and glutathione peroxidase 1, reduced ROS accumulation, and normalized levels of mitochondrial preprotein translocases of the outer membrane, and oxidative phosphorylation complexes I-V in the kidneys of mouse progeny after intrauterine cigarette smoke exposure. These findings support the hypothesis that oxidative stress and mitochondrial dysfunction are closely linked to the adverse effects of maternal smoking on male offspring renal pathology. The results of our study suggest that l-carnitine administration in cigarette smoke-exposed mothers mitigates these deleterious renal consequences.
Ashrafinia, F, Mirmohammadaili, M, Rajabi, H, Kazemnejad, A, SadeghniiatHaghughu, K, Amelvalizadeh, M & Chen, H 2014, 'The Effects of Pilates Exercise on Sleep Quality in Postpartum Women', Journal of Bodywork and Movement Therapies, vol. 18, no. 2, pp. 190-199.View/Download from: Publisher's site
Prolonged poor sleeping quality can decrease women's ability to perform their maternal and family duties after delivery. The aim of this study was to investigate the effects of a Pilates training program on sleep quality in primigravida postpartum women in a randomized clinical trial. Eighty postpartum women were randomly divided into intervention and control groups (n = 40). Home-based 30-min Pilate's exercises were started 72 h after the delivery and performed five times per week for consecutive 8 weeks. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) prior to the intervention and 4th and 8th weeks afterwards. The intervention group showed a significant improvement in subjective sleep quality, sleep latency, daytime dysfunction and global PSQI score (P < 0.001); however, there was no difference in sleep duration, habitual sleep efficiency and sleep disturbance between the groups. In conclusion, Pilates exercises appeared to improve sleep quality in primigravida postpartum women
Chen, H, Simar, D & Morris, M 2014, 'Maternal obesity impairs brain glucose metabolism and neural response to hyperglycemia in male rat offspring', Journal of Neurochemistry, vol. 1.View/Download from: Publisher's site
Hypothalamic appetite regulators neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) are modulated by glucose. This study investigated how maternal obesity disturbs glucose regulation of NPY and POMC, and whether this deregulation is linked to abnormal hypothalamic glucose uptake-lactate conversion. As post-natal high-fat diet (HFD) can exaggerate the effects of maternal obesity, its additional impact was also investigated. Female Sprague Dawley rats were fed a HFD (20 kJ/g) to model maternal obesity. At weaning, male pups were fed chow or HFD. At 9 weeks, in vivo hypothalamic NPY and POMC mRNA responses to acute hyperglycemia were measured; while hypothalami were glucose challenged in vitro to assess glucose uptake-lactate release and related gene expression. Maternal obesity dampened in vivo hypothalamic NPY response to acute hyperglycemia, and lowered in vitro hypothalamic glucose uptake and lactate release. When challenged with 20 mM glucose, hypothalamic glucose transporter 1, monocarboxylate transporters, lactate dehydrogenase-b, NPY and POMC mRNA expression were down-regulated in offspring exposed to maternal obesity. Post-natal HFD consumption reduced in vitro lactate release and monocarboxylate transporter 2 mRNA, but increased POMC mRNA levels when challenged with 20 mM glucose.
Chen, H, Simar, D, Pegg, K, Saad, S, Palmer, C & Morris, MJ 2014, 'Exendin-4 is effective against metabolic disorders induced by intrauterine and postnatal overnutrition in rodents', Diabetologia, vol. 57, no. 3.View/Download from: Publisher's site
Maternal obesity leads to increased adiposity, hyperlipidaemia and glucose intolerance in offspring. The analogue of glucagon-like peptide-1, exendin-4 (Ex-4), has been shown to induce weight loss in both adolescence and adulthood. We hypothesised that, in rats, daily injection of Ex-4 would reduce body fat and improve metabolic disorders in offspring from obese dams, especially those consuming a high-fat diet (HFD).
Female Sprague Dawley rats were fed chow or an HFD for 5 weeks before mating, and throughout gestation and lactation. At postnatal day 20, male pups from HFD-fed mothers were weaned onto chow or HFD and those from chow-fed mothers were fed chow. Within each dietary group, half of the pups were injected with Ex-4 (15 μg/kg/day i.p.) for 6 weeks, while the other half received saline.
Maternal obesity alone or combined with postweaning HFD consumption led to increased adiposity, hyperinsulinaemia, hyperlipidaemia, inflammation and impaired regulation of hypothalamic appetite regulators by glucose in offspring, while glucose intolerance was only observed in HFD-fed rats from obese dams. Ex-4 injection significantly reduced adiposity, hyperlipidaemia and insulin resistance in HFD-fed rats from obese dams. It also restored glucose tolerance and the lipid-lowering effect of blood glucose. However, Ex-4 did not change hypothalamic appetite regulation or the response of appetite regulators to hyperglycaemia. Liver and adipose inflammatory cytokine expression was significantly reduced by Ex-4.
Ex-4 reversed the detrimental impact of maternal obesity on lipid and glucose metabolism in offspring regardless of diet, supporting its potential application in reducing metabolic disorders in high-risk populations.
Saffari, M, Pakpour, AH, Mohammadi-Zeidi, I, Samadi, M & Chen, H 2014, 'Long-term effect of motivational interviewing on dietary intake and weight loss in Iranian obese/overweight women.', Health promotion perspectives, vol. 4, no. 2, pp. 206-213.View/Download from: Publisher's site
BACKGROUND: This study aimed to determine whether motivational interviewing (MI) could change dietary habit and body mass index (BMI) in obese/overweight women. METHODS: A cluster-randomized controlled study was performed in four health centers in Qazvin, central Iran. In total, 327 obese/overweight women were selected by a multi-stage sampling method and randomly assigned into control and experimental groups. Food frequency (using questionnaire; FFQ), BMI, and metabolic markers including blood pressure, total serum cholesterol and fasting blood glucose levels were measured in all participants. Data were collected twice (before and one year after the MI interventions). Data were analyzed using student t-test, and Stepwise Linear Regression. RESULTS: There was a significant increase in daily consumption of dietary fiber, whole grain products, fruits and vegetables in the MI group (P<0.05). The consumption of meat product, total fat, saturated fat, carbohydrate and total energy intake were also significantly reduced after MI intervention (P<0.05). As a result, body weight and BMI were significantly reduced in the intervention group compared to the control group (P<0.05). CONCLUSION: MI is suggested to be an effective strategy to change life style and reduce BMI in overweight/obese women in the long term. This effect needs to be further investigated in different gender and age populations.
Saffari, M, Pakpour, AH, Mohammadi-Zeidi, S, Samadi, M & Chen, H 2014, 'Long-Term Effect of Motivational Interviewing on Dietary Intake and Weight Loss in Iranian Obese/Overweight Women', Health Promot Perspect, vol. 2014, no. 2, pp. 206-213.
Zeidi, I, Saffari, M, Chen, H & Pakpour, AH 2014, 'Translation, reliability and validity of Iranian version of the smoking consequences questionnaire (SCQ) among smokers', Journal of Substance Use, vol. 19, no. 5, pp. 382-387.View/Download from: Publisher's site
Background: Smoking poses varions adverse effects on human health. Unfortunately, there is still a large population of smokers worldwide. Well understanding the potential consequences of smoking by the general public may prevent the initiation of smoking behavior and help the smokers to quit. Aims: The aim of this study was to cross-culturally translate and validate the Persian version of Smoking Consequences Questionnaire (SCQ). Design and methods: The backwardforward translation technique was used to setup the scales among 40 smokers. Using a convenient sampling method, 400 smokers were recruited from a smoking cessation department in Qazvin city. Internal consistency and testretest method was used to assess reliability. Cronbachs Alpha and Intraclass Correlation Coefficients (ICC) were used to assess Internal Consistency and Testretest reliability. Predictive validity of Nicotine Dependence was measured by correlation between SCQ and Fagerstrom Test. The scale construction was verified by Factor Analysis (explanatory and confirmatory). Data are expressed as mean?±?SD, which were analyzed by SPSS. Read More: http://informahealthcare.com/doi/abs/10.3109/14659891.2013.833654
Zhang, M, Qiu, X, Zhang, H, Yang, X, Hong, N, Yang, Y, Chen, H & Yu, C 2014, 'Faecalibacterium prausnitzii Inhibits Interleukin-17 to Ameliorate Colorectal Colitis in Rats', PLoS ONE, vol. 9, no. 10, pp. 1-10.View/Download from: Publisher's site
Background and Aims
It has been shown that Faecalibacterium prausnitzii (F. prausnitzii), one of the dominant intestinal bacterial flora, may protect colonic mucosa against the development of inflammation and subsequent inflammatory bowel disease (IBD), with the underlying mechanisms being unclear.
The impacts of F. prausnitzii and its metabolites on IL-23/Th17/IL-17 pathway markers were determined in human monocytes and a rat model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid. F. prausnitzii and its culture medium (containing complete metabolites) were used to treat the rats in vivo, as well as rat splenocytes and human monocytes in vitro. Inflammatory cytokines were measured in colon tissue, plasma and cell culture medium.
The culture supernatant of F. prausnitzii increased plasma anti-Th17 cytokines (IL-10 and IL-12)and suppressed IL-17 levels in both plasma and colonic mucosa, with ameliorated colonic colitis lesions. This inhibition of IL-17 release has also been observed in both rat splenocytes and human venous monocytes in vitro. The culture supernatant of F. prausnitzii also suppressed Th17 cell differentiation induced by cytokines (TGF-ß and IL-6) and bone marrow-derived dendritic cells (BMDCs) in vitro. The metabolites of F. prausnitzii in the culture supernatant exert a stronger anti-inflammatory effect than the bacterium itself. F. prausnitzii protected the colon mucosa against the development of IBD by its metabolites, suggesting a promising potential for the use of F. prausnitzii and its metabolic products in the treatment of IBD.
Chen, H, Al-Odat, I, Chan, Y, Amgad, S, Wong, M, Gill, A, Pollock, C & Saad, S 2014, 'The impact of maternal cigarette smoke exposure in a rodent model on renal development in the offspring', PLoS One, vol. 9, no. 7, pp. e103443-e103443.View/Download from: Publisher's site
This study aimed to investigate whether maternal cigarette smoke exposure can disrupt fetal kidney development by changing the expression of growth and transcription factors essential for renal development, and thereafter predispose the offspring to chronic kidney disease later in life. Female Balb/c mice (6 weeks) were exposed either to cigarette smoke or air under identical conditions, 6 weeks prior to mating, during gestation and during lactation. Male offspring were sacrificed at three time points, postnatal day (P)1, P20 (weaning age), and 13 weeks (mature age). Blood, urine, and kidneys were collected for analysis. At P1, the developmental genes fibroblast growth factor 2, glial cell-line derived neurotrophic factor and paired box 2 were upregulated at mRNA and protein levels; whilst fibroblast growth factor (FGF) 7 and FGF10 were downregulated. At P20, mRNA expression of FGF2, FGF10 and Wingless-type 4 was upregulated by maternal smoke exposure. These changes were normalised in adulthood. Nephron development was delayed, with fewer nephron numbers from P1 persisted to adulthood; while glomerular volume was increased at P20 but reduced in adulthood. Pro-inflammatory marker monocyte chemoatractant protein 1 (MCP1) was increased in the kidney by maternal smoke exposure. These changes were accompanied by an increased albumin/creatinine ratio in adulthood, suggesting reduced renal dysfunction. In conclusion maternal cigarette smoke exposure prior to and during pregnancy, as well as lactation leads to significant renal underdevelopment and functional abnormalities in adulthood. This study confirms the hypothesis that maternal smoking predisposes offspring to chronic kidney disorders.
Chen, H, Al-Odat, I, Pollock, C & Saad, S 2013, 'Fetal Programming of Renal Development-Influence of Maternal Smoking', Journal of Diabetes & Metabolism, vol. S9, pp. 1-7.View/Download from: Publisher's site
Smoking is a known risk factor for non-communicable illness including pulmonary disease, cardiovascular disease, and Type 2 diabetes. Smoking also contributes significantly to the rising `epidemic of chronic kidney disease. It is increasingly recognised that maternal programming of fetal development during pregnancy predisposes offspring to future disease. Maternal smoking, particularly in the first trimester, imposes a significant adverse impact on fetal renal development that determines the future risk of chronic kidney disease. Several mechanisms may contribute. Firstly, epigenetic modification of fetal nuclear or mitochondrial DNA, induced by intrauterine exposure to chemicals within the cigarette smoke, may result in an increased risk for metabolic and renal disorders. Secondly, nicotine and other chemicals within the cigarette smoke can cross the blood placental barrier concentrate in the fetus and result in direct toxicity. Thirdly, malnutrition due to the anorexigenic effect of smoking results in nutritional deficits in the fetus and impairs organ growth and development. 10-45% of pregnant women from diverse populations smoke during pregnancy. Hence it is considered a major and significant public health issue that imposes adverse health consequences not only to the pregnant women, but also inherited by their offspring, and potentially affecting future generations.
Grayson, TH, Chadha, PS, Bertrand, PP, Chen, H, Morris, MJ, Senadheera, S, Murphy, TV & Sandow, SL 2013, 'Increased caveolae density and caveolin-1 expression accompany impaired NO-mediated vasorelaxation in diet-induced obesity', Histochemistry and Cell Biology, vol. 139, no. 2, pp. 309-321.View/Download from: Publisher's site
Diet-induced obesity induces changes in mechanisms that are essential for the regulation of normal artery function, and in particular the function of the vascular endothelium. Using a rodent model that reflects the characteristics of human dietary obesity, in the rat saphenous artery we have previously demonstrated that endothelium-dependent vasodilation shifts from an entirely nitric oxide (NO)-mediated mechanism to one involving upregulation of myoendothelial gap junctions and intermediate conductance calcium-activated potassium channel activity and expression. This study investigates the changes in NO-mediated mechanisms that accompany this shift. In saphenous arteries from controls fed a normal chow diet, acetylcholine-mediated endothelium-dependent vasodilation was blocked by NO synthase and soluble guanylyl cyclase inhibitors, but in equivalent arteries from obese animals sensitivity to these agents was reduced. The expression of endothelial NO synthase (eNOS) and caveolin-3 in rat saphenous arteries was unaffected by obesity, whilst that of caveolin-1 monomer and large oligomeric complexes of caveolins-1 and -2 were increased in membrane-enriched samples. The density of caveolae was increased at the membrane and cytoplasm of endothelial and smooth muscle cells of saphenous arteries from obese rats. Dissociation of eNOS from caveolin-1, as a prerequisite for activation of the enzyme, may be compromised and thereby impair NO-mediated vasodilation in the saphenous artery from diet-induced obese rats. Such altered signaling mechanisms in obesity-related vascular disease represent significant potential targets for therapeutic intervention.
Hansen, M, Chen, H, Jones, JU, Langenbach, SY, Vlahos, R, Gualano, RC, Morris, M & Anderson, GP 2013, 'The lung inflammation and skeletal muscle wasting induced by subchronic cigarette smoke exposure are not altered by a high-fat diet in mice', PLoS One, vol. 8, no. 11, pp. e80471-e80471.View/Download from: Publisher's site
Obesity and cigarette smoking independently constitute major preventable causes of morbidity and mortality and obesity is known to worsen lung inflammation in asthma. Paradoxically, higher body mass index (BMI) is associated with reduced mortality in smoking induced COPD whereas low BMI increases mortality risk. To date, no study has investigated the effect of a dietary-induced obesity and cigarette smoke exposure on the lung inflammation and loss of skeletal muscle mass in mice. Male BALB/c mice were exposed to 4 cigarettes/day, 6 days/week for 7 weeks, or sham handled. Mice consumed either standard laboratory chow (3.5 kcal/g, 12% fat) or a high fat diet (HFD, 4.3 kcal/g, 32% fat). Mice exposed to cigarette smoke for 7 weeks had significantly more inflammatory cells in the BALF (P<0.05) and the mRNA expression of pro-inflammatory cytokines and chemokines was significantly increased (P<0.05); HFD had no effect on these parameters. Sham- and smoke-exposed mice consuming the HFD were significantly heavier than chow fed animals (12 and 13%, respectively; P<0.05). Conversely, chow and HFD fed mice exposed to cigarette smoke weighed 16 and 15% less, respectively, compared to sham animals (P<0.05). The skeletal muscles (soleus, tibialis anterior and gastrocnemius) of cigarette smoke-exposed mice weighed significantly less than sham-exposed mice (P<0.05) and the HFD had no protective effect. For the first time we report that cigarette smoke exposure significantly decreased insulin-like growth factor-1 (IGF-1) mRNA expression in the gastrocnemius and tibialis anterior and IGF-1 protein in the gastrocnemius (P<0.05).
Rajia, S, Chen, H & Morris, MJ 2013, 'Voluntary post weaning exercise restores metabolic homeostasis in offspring of obese rats', Nutrition, Metabolism & Cardiovascular Diseases, vol. 23, no. 6, pp. 574-581.View/Download from: Publisher's site
Aim Physical exercise reduces obesity, insulin resistance and dyslipidemia. We previously found that maternal obesity alters central appetite circuits and contributes to increased adiposity, glucose intolerance and metabolic disease in offspring. Here we hypothesized that voluntary exercise would ameliorate the adverse metabolic effects of maternal obesity on offspring. Methods and Results SpragueDawley females fed chow (C) or high-fat diet HFD (H) were mated. Female offspring from C dams were weaned onto chow (CC); those from H dams recieved chow (HC) or HFD (HH). Half of each group was provided with running wheels (CCEX, HCEX, HHEX; n = 1012). Maternal obesity increased body weight (12%), adiposity, plasma lipids and induced glucose intolerance (HC vs CC; P < 0.05). These were exaggerated by postweaning HFD (HH vs HC; P < 0.01), showed doubled energy intake, a 37% increase in body weight, insulin resistance and glucose intolerance (HH vs HC; P < 0.01). Exercise reduced fat mass, plasma lipids, HOMA and fasting glucose in HCEX (vs HC; P < 0.05) and HHEX (vs HH; P < 0.01). Values in HCEX were indistinguishable from CC, however in HHEX these metabolic parameters remained higher than the sedentary HC and CC rats (P < 0.01). mRNA expression of hypothalamic pro-opiomelanocortin, and adipose tumour necrosis factor a and 11ß-hydroxysteroid dehydrogenase type 1 were reduced by exercise in HHEX (vs HH; P < 0.05).
Chen, H, Dorrigan, A, Saad, S, Hare, DJ, Cortie, MB & Valenzuela, S 2013, 'In Vivo Study of Spherical Gold Nanoparticles: Inflammatory Effects and Distribution in Mice', PLoS One, vol. 8, no. 2, pp. 1-8.View/Download from: Publisher's site
Objectives Gold nanoparticles (AuNPs) of 21 nm have been previously well characterized in vitro for their capacity to target macrophages via active uptake. However, the short-term impact of such AuNPs on physiological systems, in particular resident macrophages located in fat tissue in vivo, is largely unknown. This project investigated the distribution, organ toxicity and changes in inflammatory cytokines within the adipose tissue after mice were exposed to AuNPs. Methods Male C57BL/6 mice were injected intraperitoneally (IP) with a single dose of AuNPs (7.85 µg AuNPs/g). Body weight and energy intake were recorded daily. Tissues were collected at 1 h, 24 h and 72 h post-injection to test for organ toxicity. AuNP distribution was examined using electron microscopy. Proinflammatory cytokine expression and macrophage number within the abdominal fat pad were determined using real-time PCR.
Cortie, MB, Al Hafed, E, Chen, H, Valenzuela, S, Ting, S, Sonvico, F & Milthorpe, BK 2013, 'Nanomedical research in Australia and New Zealand', Nanomedicine, vol. 8, no. 12, pp. 1999-2006.View/Download from: Publisher's site
Although Australia and New Zealand have a combined population of less than 30 million, they have an active and interlinked community of nanomedical researchers. This report provides a synopsis and update on this network with a view to identifying the main topics of interest and their likely future trajectories. In addition, our report may also serve to alert others to opportunities for joint projects. Australian and New Zealand researchers are engaged in most of the possible nanomedical topics, but the majority of interest is focused on drug and nucleic acid delivery using nanoparticles or nanoporous constructs. There are, however, smaller programs directed at hyperthermal therapy and radiotherapy, various kinds of diagnostic tests and regenerative technologies.
Bertrand, RL, Senadheera, S, Tanoto, A, Tan, KL, Howitt, L, Chen, H, Murphy, TV, Sandow, SL, Liu, L & Bertrand, PP 2012, 'Serotonin availability in rat colon is reduced during a Western diet model of obesity', AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, vol. 303, no. 3, pp. G424-G434.View/Download from: Publisher's site
Chen, H, Saad, S, Sandow, SL & Bertrand, PP 2012, 'Cigarette smoking and brain regulation of energy homeostasis', Frontiers in Pharmacology, vol. 3, no. 147, pp. 1-8.View/Download from: Publisher's site
Cigarette smoking is an addictive behavior, and is the primary cause of cardiovascular and pulmonary disease, and cancer (among other diseases). Cigarette smoke contains thousands of components that may affect caloric intake and energy expenditure, although nicotine is the major addictive substance present, and has the best described actions. Nicotine exposure from cigarette smoke can change brain feeding regulation to reduce appetite via both energy homeostatic and reward mechanisms, causing a negative energy state which is characterized by reduced energy intake and increased energy expenditure that are linked to low body weight. These findings have led to the public perception that smoking is associated with weight loss. However, its effects at reducing abdominal fat mass (a predisposing factor for glucose intolerance and insulin resistance) are marginal, and its promotion of lean body mass loss in animal studies suggests a limited potential for treatment in obesity. Smoking during pregnancy puts pressure on the mothers metabolic system and is a significant contributor to adverse pregnancy outcomes.
Chen, H, Simar, D, Ting, HJ, Erkelens, JR & Morris, MJ 2012, 'Leucine improves glucose and lipid status in offspring from obese dams, dependent on diet type, but not caloric intake', Journal of Neuroendocrinology, vol. 24, no. 10, pp. 1356-1364.View/Download from: Publisher's site
Previously, we showed that offspring from obese rat dams were hyperphagic, with increased adiposity, hyperlipidaemia and glucose intolerance associated with increased orexigenic neuropeptide expression after fasting. Mammalian target of rapamycin (mTOR) can inhibit food intake through a hypothalamic action. As we previously showed that maternal obesity down-regulated hypothalamic mTOR, in the present study, we hypothesised that dietary leucine supplementation would activate hypothalamic mTOR to reduce food intake, thus limiting metabolic disorders in offspring from obese dams, regardless of postweaning diet. Obesity was induced in SpragueDawley females by high-fat diet (HFD) for 5 weeks before mating, throughout gestation and lactation. Male pups from HFD-fed mothers were weaned onto chow or HFD; within each dietary group, half were supplied with leucine via drinking water (1.5%) versus water control for 10 weeks. Those from chow-fed mothers were fed chow and water. Maternal obesity led to increased adiposity in chow-fed offspring. Postweaning HFD consumption exaggerated adiposity, hyperglycaemia, hyperinsulinaemia and hyperlipidaemia. Supplementation with leucine doubled leucine intake and increased hypothalamic mTOR activation; however, appetite regulation was not affected. A reduction in blood lipid levels was observed in offspring regardless of diet, as well as improved glucose tolerance in HFD-fed rats. In HFD-fed rats, up-regulated carnitine palmitoyl-transferase-1 and peroxisome-proliferator-activated receptor-? coactivator-1a in muscle and glucose transporter 4 in fat suggested that leucine improved peripheral fat oxidation and glucose transport. Leucine is able to improve peripheral glucose and lipid metabolism independent of appetite and weight regulation, suggesting its potential application in the management of metabolic disorder
Simar, D, Chen, H, Lambert, K, Mercier, J & Morris, MJ 2012, 'Interaction between maternal obesity and post-natal over-nutrition on skeletal muscle metabolism', Nutrition, Metabolism & Cardiovascular Diseases, vol. 22, pp. 269-276.View/Download from: Publisher's site
Background and aims: Maternal obesity and post-natal over-nutrition play an important role in programming glucose and lipid metabolism later in life. The aim of this study was to decipher the contributions of maternal obesity and post-natal over-nutrition on glucose and lipid metabolism in skeletal muscle. Method and results: Male offspring of Sprague Dawley rat mothers fed either chow or high fat diet (HFD) for 5 weeks prior to mating were subsequently fed either chow or HFD until 18 weeks of age. Collection of plasma and skeletal muscle was performed at weaning (20 days) and 18 weeks. At weaning, offspring from obese mothers showed increased body weight, plasma insulin and lactate concentrations associated with reduced skeletal muscle glucose transporter 4 (GLUT4) and increased monocarboxylate transporter 1 (MCT1) protein. In 18-week old offspring, post-weaning HFD further exacerbated the elevated body weight caused by maternal obesity. Surprisingly this additive effect on body weight was not reflected in plasma glucose, insulin, lactate and MCT1; these markers were only increased by post-weaning HFD consumption. However, an additive effect of maternal obesity and post-weaning HFD led to decreased muscle GLUT4 levels, as well as mRNA levels of carnitine palmitoyl transferase-1, myogenic differentiation protein and myogenin. Conclusion: Post-weaning HFD exerted an additive effect to that of maternal obesity on body weight and skeletal muscle markers of glucose and lipid metabolism but not on plasma glucose and insulin levels, suggesting that maternal obesity and post-natal over-nutrition impair skeletal muscle function via different mechanisms.
Bertrand, RL, Senadheera, S, Markus, I, Liu, L, Howitt, L, Chen, H, Murphy, TV, Sandow, SL & Bertrand, PP 2011, 'A Western diet increases serotonin availability in rat small intestine', No Code, vol. 152, no. 1, pp. 36-47.View/Download from: Publisher's site
Diet-induced obesity is associated with changes in gastrointestinal function and induction of a mild inflammatory state. Serotonin (5-HT) containing enterochromaffin (EC) cells within the intestine respond to nutrients and are altered by inflammation. Thus, our aim was to characterize the uptake and release of 5-HT from EC cells of the rat ileum in a physiologically relevant model of diet-induced obesity. In chow-fed (CF) and Western dietfed (WD) rats electrochemical methods were used to measure compression evoked (peak) and steady state (SS) 5-HT levels with fluoxetine used to block the serotonin reuptake transporter (SERT). The levels of mRNA for tryptophan hydroxylase 1 (TPH1) and SERT were determined by quantitative PCR, while EC cell numbers were determined immunohistochemically. In WD rats, the levels of 5-HT were significantly increased (SS: 19.2±3.7 µM; peak: 73.5±14.1 µM) compared with CF rats (SS: 12.3±1.8 µM; peak: 32.2±7.2 µM), while SERT-dependent uptake of 5-HT was reduced (peak WD: 108% of control versus peak CF: 212% control). In WD rats, there was a significant increase in TPH1 mRNA, a decrease in SERT mRNA and protein, and an increase in EC cells. In conclusion, our data show that foods typical of a Western diet are associated with an increased 5-HT availability in the rat ileum. Increased 5-HT availability is driven by the up-regulation of 5-HT synthesis genes, decreased re-uptake of 5-HT, and increased numbers and/or 5-HT content of EC cells which are likely to cause altered intestinal motility and sensation in vivo.
Caruso, V, Chen, H & Morris, M 2011, 'Early hypothalamic FTO overexpression in response to maternal obesity - potential contribution to postweaning hyperphagia', Plos One, vol. 6, no. 9, pp. 1-7.View/Download from: Publisher's site
Background: Intrauterine and postnatal overnutrition program hyperphagia, adiposity and glucose intolerance in offspring. Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene have been linked to increased risk of obesity. FTO is highly expressed in hypothalamic regions critical for energy balance and hyperphagic phenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolic function, we investigated the impact of maternal obesity on FTO. Methods: Female Sprague Dawley rats were exposed to chow or high fat diet (HFD) for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1 (PND1), some litters were adjusted to 3 pups (vs. 12 control) to induce postnatal overnutrition. At PND20, rats were weaned onto chow or HFD for 15 weeks. FTO mRNA expression in the hypothalamus and liver, as well as hepatic markers of lipid metabolism were measured. Results: At weaning, hypothalamic FTO mRNA expression was increased significantly in offspring of obese mothers and FTO was correlated with both visceral and epididymal fat mass (P<0.05); body weight approached significance (P = 0.07). Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. Postnatal HFD feeding significantly reduced hepatic Carnitine Palmitoyltransferase-1a but did not affect the expression of other hepatic markers investigated. FTO was not affected by chronic HFD feeding. Significance: Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning.
Chen, H, Iglesias, MA, Caruso, V & Morris, M 2011, 'Maternal cigarette smoke exposure contributes to glucose intolerance and decreased brain insulin action in mice offspring independent of maternal diet', Plos One, vol. 6, no. 11, pp. 1-11.View/Download from: Publisher's site
Background: Maternal smoking leads to intrauterine undernutrition and is associated with low birthweight and higher risk of offspring obesity. Intrauterine smoke exposure (SE) may alter neuroendocrine mediators regulating energy homeostasis as chemicals in cigarette smoke can reach the fetus. Maternal high-fat diet (HFD) consumption causes fetal overnutrition; however, combined effects of HFD and SE are unknown. Thus we investigated the impact of combined maternal HFD and SE on adiposity and energy metabolism in offspring. Method: Female Balb/c mice had SE (2 cigarettes/day, 5 days/week) or were sham exposed for 5 weeks before mating. Half of each group was fed HFD (33% fat) versus chow as control. The same treatment continued throughout gestation and lactation. Female offspring were fed chow after weaning and sacrificed at 12 weeks. Results: Birthweights were similar across maternal groups. Faster growth was evident in pups from SE and/or HFD dams before weaning. At 12 weeks, offspring from HFD-fed dams were significantly heavier than those from chow-fed dams (chow-sham 17.6 +/- 0.3 g; chow-SE 17.8 +/- 0.2 g; HFD-sham 18.7 +/- 0.3 g; HFD-SE 18.8 +/- 0.4 g, P<0.05 maternal diet effect); fat mass was significantly greater in offspring from chow+SE, HFD+SE and HFD+sham dams. Both maternal HFD and SE affected brain lactate transport. Glucose intolerance and impaired brain response to insulin were observed in SE offspring, and this was aggravated by maternal HFD consumption. Conclusion: While maternal HFD led to increased body weight in offspring, maternal SE independently programmed adverse health outcomes in offspring. A smoke free environment and healthy diet during pregnancy is desirable to optimize offspring health.
Pakpour, AH, Yekaninejad, M & Chen, H 2011, 'Mothers' Perception Of Obesity In Schoolchildren: A Survey And The Impact Of An Educational Intervention', Jornal de Pediatria, vol. 87, no. 2, pp. 169-174.View/Download from: Publisher's site
Objectives: To investigate mothers' awareness of their children's weight problem, and to evaluate the impact of an educational intervention on improving mothers' recognition of obesity in their children. Methods: Twelve primary schools from Tehran, Iran,
Rajia, S, Chen, H & Margaret, JM 2010, 'Maternal overnutrition impacts offspring adiposity and brain appetite markers-modulation by postweaning diet', Journal of Neuroendocrinology, vol. 22, no. 8, pp. 905-914.View/Download from: Publisher's site
Maternal obesity has long-term consequences for the development of hypothalamic neurones involved in energy homeostasis and the metabolic profile in offspring. In the present study, we compared the effects of maternal obesity induced by longstanding high-fat diet (HFD) with milder postnatal overfeeding during suckling induced by litter size reduction. Female SpragueDawley rats consumed chow (C) or HFD. On postnatal day 1, litters from chow dams were adjusted to three per dam (small litter, CS) versus 12 control (normal litter, CN). Litters from HFD dams were adjusted to 12 per dam and fed HFD after weaning to induce obesity (HN). Thus, two degrees of maternal overnutrition were produced (CS and HN). To test whether postweaning diet can amplify the effects of maternal obesity, male offspring weaned onto chow or HFD were followed to 21 weeks. Maternal postnatal overnutrition (CS) and HFD-induced maternal obesity (HN) increased body weight and fat mass in offspring compared to those from control dams (CN). Significant glucose intolerance was induced by both degrees of maternal overnutrition, but only in offspring consuming HFD. HFD-induced maternal obesity (HN) was linked to increased offspring leptin, insulin, lipids, insulin resistance and hyperphagia, and was exaggerated by postweaning HFD. No effect of maternal postnatal overnutrition (CS) was seen on these parameters. Hypothalamic signal transducer and activator of transcription-3 and suppressor of cytokine signalling-3 mRNA were significantly elevated by maternal HFD (HN) in the HFD-fed offspring. The data obtained suggest that even mild maternal overnutrition (CS) led to increased adiposity, glucose intolerance and altered brain appetite regulators in offspring. A greater impact of HFD-induced maternal obesity was evident. Marked additive effects were observed when animals consumed a HFD postweaning.
Chen, H, Li, K & Shan, ZH 2009, 'Ternary reaction of resorcinol-oxazolidine-glycin', Sichuan Daxue Xuebao (Gongcheng Kexue Ban)/Journal of Sichuan University (Engineering Science Edition), vol. 41, no. 1, pp. 91-95.
The Tanning Matrix can be formed by resorcinol and oxazolidine E, and the reactioncharateristics between Tanning Matrix and collagen were investigated through NMR and size distribution analysis. The collagen was simulated with glycin. The results showed that the molar combination ratio of Matrix as congeries between oxazolidine E and resorcinol was 2:1 or 3:2, the reaction positions were C (5) and C (6) of oxazolidine E and C (4) or C (6) of resorcinol. The hydroxymethyl of oxazolidine E bonded the amino group of collagen with covalent bond, and the phenol hydroxyl group of resorcinol combined the amino group of collagen with hydrogen bond.
Maternal obesity due to long-term high-fat diet (HFD) consumption leads to faster growth in offspring during suckling, and increased adiposity at 20 days of age. Decreased expression of the orexigenic neuropeptide Y (NPY) and increased anorexigenic proopiomelanocortin (POMC) mRNA expression were observed in the fed state. However, hunger is the major drive to eat and hypothalamic appetite regulators change in response to meals. Therefore it is important to compare both satiated and fasting states. Female Sprague Dawley rats (8 weeks old) were fed a cafeteria-style HFD (15.33kJ/g) or chow for 5 weeks before mating, with the same diet continuing throughout gestation and lactation. At postnatal day 20, male pups were killed either after overnight fasting or in the fed state. Pups from obese dams were hyperphagic during both pre- and post-weaning periods. Pups from obese dams had higher hypothalamic mRNA expression of POMC and NPY Y1 receptor, but lower hypothalamic melanocortin-4 receptor (MC4R) and its downstream target single-minded gene 1 (Sim1), in the fed state. Overnight fasting reduced circulating glucose, insulin, and leptin and increased hypothalamic NPY Y1 receptor mRNA in pups from both lean and obese dams. Hypothalamic NPY and agouti-related protein were only increased by fasting in pups from obese dams; reductions in MC4R and Sim1 were only seen in pups from lean dams. At weaning, the suppressed orexigenic signals in offspring from obese dams were normalized after overnight fasting, while anorexigenic signaling appeared impaired in these animals. This may contribute to their hyperphagia and faster growth.
Chen, H, Simar, D & Margaret, JM 2009, 'Hypothalamic neuroendocrine circuitry is programmed by maternal obesity: interaction with postnatal nutritional environment', PLoS ONE, vol. 4, no. 7, pp. 1-10.View/Download from: Publisher's site
Early life nutrition is critical for the development of hypothalamic neurons involved in energy homeostasis. We previously showed that intrauterine and early postnatal overnutrition programmed hypothalamic neurons expressing the appetite stimulator neuropeptide Y (NPY) and suppressor proopiomelanocortin (POMC) in offspring at weaning. However, the long-term effects of such programming and its interactions with post-weaning high-fat-diet (HFD) consumption are unclear.
Morris, M & Chen, H 2009, 'Established maternal obesity in the rat reprograms hypothalamic appetite regulators and leptin signaling at birth', International Journal of Obesity, vol. 33, no. 1, pp. 115-122.View/Download from: Publisher's site
Objective:Key appetite regulators and their receptors are already present in the fetal hypothalamus, and may respond to hormones such as leptin. Intrauterine food restriction or hyperglycemia can reprogram these circuits, possibly predisposing individuals to adverse health outcomes in adulthood. Given the global obesity epidemic, maternal overweight and obesity is becoming more prevalent. Earlier, we observed rapid growth of pups from obese dams during the suckling period. However, it is unclear whether this is because of alterations in leptin and hypothalamic appetite regulators at birth.Design:Female SpragueDawley rats were fed palatable high-fat diet (HFD) or chow for 5 weeks to induce obesity before mating. The same diet continued during gestation. At day 1, after birth, plasma and hypothalamus were collected from male and female pups.Measurements:Body weight and organ mass were recorded. Leptin and insulin levels were measured in the plasma by radioimmunoassay. Hypothalamic mRNA expression of neuropeptide-Y (NPY), pro-opiomelanocortin, leptin receptor and its downstream signal, STAT3 (signal transducer and activator of transcription 3), were measured using real-time PCR.Results:Body and organ weights of pups from obese dams were similar to those from lean dams, across both genders. However, plasma leptin levels were significantly lower in offspring from obese dams (male: 0.53±0.13 vs 1.05±0.21 ng ml-1; female: 0.33±0.09 vs 2.12±0.57 ng ml-1, respectively; both P<0.05).
Shiraev, T, Chen, H & Morris, MJ 2009, 'Differential effects of restricted versus unlimited high-fat feeding in rats on fat mass, plasma hormones and brain appetite regulators', Journal of Neuroendocrinology, vol. 21, no. 7, pp. 602-609.View/Download from: Publisher's site
The rapid rise in obesity has been linked to altered food consumption patterns. There is increasing evidence that, in addition to total energy intake, the macronutrient composition of the diet may influence the development of obesity. The present study aimed to examine the impact of high dietary fat content, under both isocaloric and hypercaloric conditions, compared with a low fat diet, on adiposity, glucose and lipid metabolism, and brain appetite regulators in rats. Male Sprague-Dawley rats were exposed to one of three diets: control (14% fat), ad lib high-fat palatable (HFD, 35% fat) or high-fat palatable restricted (HFD-R, matched to the energy intake of control) and were killed in the fasting state 11 weeks later. Body weight was increased by 28% in unrestricted HFD fed rats, with an almost tripling of caloric intake and fat mass (P < 0.001) and double the plasma triglycerides of controls. Glucose intolerance and increased insulin levels were observed. HFD-R animals calorie matched to control had double their fat mass, plasma insulin and triglycerides (P < 0.05). Only ad lib consumption of the HFD increased the hypothalamic mRNA expression of the appetite-regulating peptides, neuropeptide Y and pro-opiomelanocortin. Although restricted consumption of palatable HFD had no significant impact on hypothalamic appetite regulators or body weight, it increased adiposity and circulating triglycerides, suggesting that the proportion of dietary fat, independent of caloric intake, affects fat deposition and the metabolic profile.
Chen, H, Hansen, M, Jones, JE, Vlahos, R & Morris, M 2008, 'Long-term cigarette smoke exposure increases uncoupling protein expression but reduces energy intake', Brain Research, vol. 1228, no. 4, pp. 81-88.View/Download from: Publisher's site
The appetite suppressing effect of tobacco is a major driver of smoking behaviour; however few studies have addressed the effects of chronic cigarette smoke exposure (SE) on appetite, body weight and metabolic markers. We compared the effects of SE to equivalent food restriction (pair-fed, PF), against sham-exposure, on body weight, adiposity, cytokines, and levels of uncoupling proteins (UCP) and brain neuropeptide Y (NPY) in male Balb/C mice. SE rapidly induced anorexia, and after 12 weeks, SE and PF groups were lighter than control animals (23.9 ± 0.2, 25.5 ± 0.5, 26.8 ± 0.4 g respectively, P < 0.05). White fat (WAT) masses were reduced by both SE and PF. Plasma leptin and insulin were reduced in SE mice; insulin was further reduced by PF. Brown fat UCP1 and 3 mRNA were increased in SE animals relative to PF animals, possibly promoting thermogenesis. WAT mRNA expression of the inflammatory cytokine, TNF? was doubled by SE, while IL-6 was reduced by both PF and SE. Hypothalamic NPY content was increased by SE (89.3 ± 2.8 vs. 75.9 ± 2.4 ng control, P < 0.05), and more by PF (100.7 ± 3.4 ng, P < 0.05 compared to both groups), suggesting disinhibition due to reduced adipose derived leptin. In contrast to equivalent food restriction, cigarette smoke exposure reduced body weight and total hypothalamic NPY, and increased thermogenesis and markers of inflammation. The suppressed hypothalamic NPY and increased UCPs may contribute to the spontaneous hypophagia and extra weight loss in SE animals. These findings contribute to our understanding of weight loss in smoking-related lung disease, suggesting a greater impact than that due to anorexia alone.
Chen, H, Simar, D, Lambert, K, Mercier, J & Morris, M 2008, 'Maternal and postnatal overnutrition differentially impact appetite regulators and fuel metabolism', Endocrinology, vol. 149, no. 11, pp. 5348-5356.View/Download from: Publisher's site
Maternal obesity is increasing, and it is known that the intrauterine experience programs fetal and newborn metabolism. However, the relative contributions of pre- or postnatal factors are unknown. We hypothesized that maternal overnutrition caused by long-term maternal obesity would exert a stronger detrimental impact than postnatal overnutrition on offspring metabolic homeostasis, with additional postnatal overnutrition exaggerating these alterations. Female Sprague Dawley rats were exposed to chow or high-fat cafeteria diet for 5 wk before mating and throughout gestation and lactation. On postnatal d 1, litters were adjusted to three per litter to induce postnatal overnutrition (vs. 12 in control). Hypothalamic appetite regulators neuropeptide Y and proopiomelanocortin, glucose transporter 4, and lipid metabolic markers were measured. At postnatal d 20, male pups born of obese dams, or those overnourished postnatally, were 42% heavier than controls; combining both interventions led to 80% greater body weight. Maternal obesity increased pup adiposity and led to glucose intolerance in offspring; these were exaggerated by additional postnatal overnutrition during lactation. Maternal obesity was also linked to hyperlipidemia in offspring and reduced hypothalamic neuropeptide Y and increased proopiomelanocortin mRNA expression. Postnatal overnutrition of offspring from obese dams amplified these hypothalamic changes. Both maternal and postnatal overnutrition reduced muscle glucose transporter 4. Adipose carnitine palmitoyl-transferase-1 and adipose triglyceride lipase mRNA was up-regulated only by postnatal overnutrition. Maternal overnutrition appears to alter central appetite circuits and promotes early-onset obesity; postnatal overnutrition interacted to cause peripheral lipid and glucose metabolic disorders, supporting the critical message to reduce early-life adverse nutritional impact.
Morris, MJ, Chen, H, Watts, R, Shulkes, A & Cameron-Smith, D 2008, 'Brain neuropeptide Y and CCK, and peripheral adipokine receptors: temporal response to palatable diet induced obesity.', International Journal of Obesity, vol. 32, no. 2, pp. 249-258.View/Download from: Publisher's site
Objective: Palatable food disrupts normal appetite regulation, which may contribute to the etiology of obesity. Neuropeptide Y (NPY) and cholecystokinin play critical roles in the regulation of food intake and energy homeostasis, while adiponectin and carnitine palmitoyltransferase (CPT) are important for insulin sensitivity and fatty acid oxidation. This study examined the impact of short- and long-term consumption of palatable high-fat diet (HFD) on these critical metabolic regulators. Methods: Male C57BL/6 mice were exposed to laboratory chow (12% fat), or cafeteria-style palatable HFD (32% fat) for 2 or 10 weeks. Body weight and food intake were monitored throughout. Plasma leptin, hypothalamic NPY and cholecystokinin, and mRNA expression of leptin, adiponectin, their receptors and CPT-1, in fat and muscles were measured. Results: Caloric intake of the palatable HFD group was 23 times greater than control, resulting in a 37% higher body weight. Fat mass was already increased at 2 weeks; plasma leptin concentrations were 2.4 and 9 times higher than control at 2 and 10 weeks, respectively. Plasma adiponectin was increased at 10 weeks. Muscle adiponectin receptor 1 was increased at 2 weeks, while CPT-1 mRNA was markedly upregulated by HFD at both time points. Hypothalamic NPY and cholecystokinin content were significantly decreased at 10 weeks. Conclusion: Palatable HFD induced hyperphagia, fat accumulation, increased adiponectin, leptin and muscle fatty acid oxidation, and reduced hypothalamic NPY and cholecystokinin. Our data suggest that the adaptive changes in hypothalamic NPY and muscle fatty acid oxidation are insufficient to reverse the progress of obesity and metabolic consequences induced by a palatable HFD.
The prevalence of obesity is increasing worldwide, and the rising number of obese children and adolescents is of particular concern. In humans, smoking is a predisposing factor for abdominal obesity, glucose intolerance and insulin resistance. Maternal smoking is associated with preterm birth and low birth weight. On the other hand, the incidence of obesity is higher in children and adults born of smoking mothers. Disorders in eating behaviour, reduced physical activity, and increased risk of hypertension and nicotine addiction have been observed in the offspring of smoking mothers. Evidence from animal and human studies suggests that intrauterine smoke exposure may alter peripheral and central mediators involved in the regulation of appetite and energy metabolism. Smoking cessation during pregnancy is desirable to improve health outcomes in offspring.
Chen, H, Hansen, M, Jones, JE, Vlahos, R, Anderson, G & Morris, M 2007, 'Detrimental metabolic effects of combining long term cigarette smoke exposure and high-fat diet in mice', AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, vol. 293, no. 6, pp. 1564-1571.View/Download from: Publisher's site
Obesity and cigarette smoking are both important risk factors for insulin resistance, cardiovascular disease, and cancer. Smoking reduces appetite, which makes many people reluctant to quit. Few studies have documented the metabolic impact of combined smoke exposure (se) and high-fat-diet (HFD). Neuropeptide Y (NPY) is a powerful hypothalamic feeding stimulator that promotes obesity. We investigated how chronic se affects caloric intake, adiposity, plasma hormones, inflammatory mediators, and hypothalamic NPY peptide in animals fed a palatable HFD. Balb/c mice (5 wk old, male) were exposed to smoke (2 cigarettes, twice/day, 6 days/wk, for 7 wk) with or without HFD. Sham-exposed mice were handled similarly without se. Plasma leptin, hypothalamic NPY, and adipose triglyceride lipase (ATGL) mRNA were measured. HFD induced a 2.3-fold increase in caloric intake, increased adiposity, and glucose in both sham and se cohorts. Smoke exposure decreased caloric intake by 23%, with reduced body weight in both dietary groups. Fat mass and glucose were reduced only by se in the chow-fed animals. ATGL mRNA was reduced by HFD in se animals. Total hypothalamic NPY was reduced by HFD, but only in sham-exposed animals; se increased arcuate NPY. We conclude that although se ameliorated hyperphagia and reversed the weight gain associated with HFD, it failed to reverse fat accumulation and hyperglycemia. The reduced ATGL mRNA expression induced by combined HFD and se may contribute to fat retention. Our data support a powerful health message that smoking in the presence of an unhealthy Western diet increases metabolic disorders and fat accumulation.
Chen, H, Hansen, M, Jones, JE, Vlahos, R, Bozinovski, S, Anderson, G & Morris, M 2007, 'Regulation of hypothalamic NPY by diet and smoking', Peptides, vol. 28, no. 2, pp. 384-389.View/Download from: Publisher's site
Appetite is regulated by a number of hypothalamic neuropeptides including neuropeptide Y (NPY), a powerful feeding stimulator that responds to feeding status, and drugs such as nicotine and cannabis. There is debate regarding the extent of the influence of obesity on hypothalamic NPY. We measured hypothalamic NPY in male SpragueDawley rats after short or long term exposure to cafeteria-style high fat diet (32% energy as fat) or laboratory chow (12% fat). Caloric intake and body weight were increased in the high fat diet group, and brown fat and white fat masses were significantly increased after 2 weeks. Hypothalamic NPY concentration was only significantly decreased after long term consumption of the high fat diet. Nicotine decreases food intake and body weight, with conflicting effects on hypothalamic NPY reported. Body weight, plasma hormones and brain NPY were investigated in male Balb/c mice exposed to cigarette smoke for 4 days, 4 and 12 weeks. Food intake was significantly decreased by smoke exposure (2.32 ± 0.03 g/24 h versus 2.71 ± 0.04 g/24 h in control mice (non-smoke exposed) at 12 weeks). Relative to control mice, smoke exposure led to greater weight loss, while pair-feeding the equivalent amount of chow caused an intermediate weight loss. Chronic smoke exposure, but not pair-feeding, was associated with decreased hypothalamic NPY concentration, suggesting an inhibitory effect of cigarette smoking on brain NPY levels. Thus, consumption of a high fat diet and smoke exposure reprogram hypothalamic NPY. Reduced NPY may contribute to the anorexic effect of smoke exposure.
Chen, H, Hansen, M, Jones, JE, Vlahos, R, Bozinovski, S, Anderson, G & Morris, M 2006, 'Cigarette smoke exposure reprograms the hypothalamic neuropeptide Y axis to promote weight loss', American Journal of Respiratory and Critical Care Medicine, vol. 173, no. 11, pp. 1248-1254.View/Download from: Publisher's site
RATIONALE: Despite irrefutable epidemiologic evidence, cigarette smoking remains the major preventable cause of lung disease morbidity worldwide. The appetite-suppressing effect of tobacco is a major behavioral determinant of smoking, but the underlying molecular and neuronal mechanisms are not understood. Neuropeptide Y (NPY) is an orexigenic neuropeptide, whose activity in the hypothalamic paraventricular nucleus governs appetite. OBJECTIVES: To compare the effects of smoke exposure and equivalent food restriction on body weight, organ mass, cytokines, and brain NPY in Balb/c mice. METHODS: A pair-feeding study design compared smoke exposure (4 wk; 1 cigarette, 3 x /d, 5 d/wk) to equivalent food restriction (pair-fed) and sham-exposed control mice. RESULTS: Smoke exposure rapidly induced mild anorexia. After 4 wk, smoke-exposed and pair-fed groups were lighter than control mice (22.0 +/- 0.2, 23.2 +/- 0.5, 24.9 +/- 0.4 g, respectively; p < 0.05). Brown and white fat masses were only reduced by smoke exposure, relative to control mice. NPY concentration in the paraventricular nucleus was significantly and paradoxically reduced by smoke exposure, despite lower plasma leptin concentrations; this was not observed in the pair-fed group experiencing 19% food restriction. Adipose mRNA expression of uncoupling proteins, inflammatory cytokines interleukin 6 and tumor necrosis factor alpha, and adipose triglyceride lipase was decreased by smoke exposure, and even lower in pair-fed mice. CONCLUSIONS: In contrast to food restriction, smoke exposure caused a reduction in hypothalamic NPY and fat mass, and regulated adipose cytokines. These findings may contribute to understanding weight loss in smoking-related lung disease and in the design of more effective smoking cessation strategies.
Chen, H, Kent, S & Morris, M 2006, 'Is the CCK2 receptor essential for normal regulation of body weight and adiposity?', European Journal of Neuroscience, vol. 24, no. 5, pp. 1427-1433.View/Download from: Publisher's site
Cholecystokinin (CCK) is a gastrointestinal satiety signal released from the duodenum to terminate feeding, via CCK1 receptors. CCK2 receptors are considered to be involved in anxiety. CCK2 receptor knockout mice have increased body weight and food intake. Little is known regarding the effects of CCK2 receptor deficiency on adipose distribution and hypothalamic feeding regulators such as neuropeptide Y (NPY), a powerful stimulator of feeding. Adult (10?week) CCK2 receptor knockout and wild-type mice were anaesthetized and killed by decapitation. Brain sections, organs and fat tissue were dissected. Plasma leptin, insulin and brain NPY content were measured by radioimmunoassay. Female CCK2 receptor knockout mice weighed more than control mice (22.0?±?0.2 vs. 19.9?±?0.4?g, P?<?0.05), with this difference being less marked in male mice (26.4?±?0.4 vs. 25.6?±?0.6?g). Fat masses in all locations sampled were significantly smaller in CCK2 receptor knockout mice of both genders (P?<?0.05), resulting in lower plasma leptin and insulin levels. NPY concentrations were significantly increased in arcuate nucleus and anterior hypothalamus in both male and female CCK2 receptor knockout mice, and total hypothalamic NPY content was increased by 7 and 9% in males and females, respectively (P?<?0.05). CCK2 receptor deletion was associated with increased body weight and hypothalamic NPY content, but reduced fat masses and plasma leptin and insulin. Increased NPY might contribute to increased food intake in CCK2 receptor knockout mice. Further work needs to focus on the metabolic changes
Chen, H, Vlahos, R, Bozinovski, S, Jones, JE, Anderson, G & Margaret, JM 2005, 'Effect of short-term cigarette smoke exposure on body weight, appetite and brain neuropeptide Y in mice', Neuropsychopharmacology, vol. 30, no. 4, pp. 713-719.View/Download from: Publisher's site
Although nicotinic receptors have been demonstrated in hypothalamic appetite-regulating areas and nicotine administration alters food intake and body weight in both animals and humans, the mechanisms underlying the effects of smoking on appetite circuits remain unclear. Conflicting effects of nicotine on the major orexigenic peptide, neuropeptide Y (NPY), have been observed in the brain, but the effects of smoking are unknown. Thus, we aimed to investigate how cigarette smoking affects body weight, food intake, plasma leptin concentration, hypothalamic NPY peptide, adipose mass and mRNA expression of uncoupling proteins (UCP), and tumor necrosis factor (TNF) a. Balb/C mice (8 weeks) were exposed to cigarette smoke (three cigarettes, three times a day for 4 consecutive days) or sham exposed. Body weight and food intake were recorded. Plasma leptin and brain NPY were measured by radioimmunoassay. UCPs and TNF a mRNA were measured by real-time PCR. Food intake dropped significantly from the first day of smoking, and weight loss became evident within 2 days. Brown fat and retroperitoneal white fat masses were significantly reduced, and plasma leptin concentration was decreased by 34%, in line with the decreased fat mass. NPY concentrations in hypothalamic subregions were similar between two groups. UCP1 mRNA was decreased in white fat and UCP3 mRNA increased in brown fat in smoking group. Short-term cigarette smoke exposure led to reduced body weight, food intake, and fat mass. The reduction in plasma leptin concentration may have been too modest to increase NPY production; alternatively, change in NPY or its function might have been offset by nicotine or other elements in cigarette smoke.
Shi, QL, Fan, KW & Chen, H 2000, 'Localized amyloidosis of cervical lymph nodes', CHINESE MEDICAL JOURNAL, vol. 113, no. 2, pp. 184-185.
Chen, H, Chan, YL, Oliver, B, Pollock, C & Saad, S 2019, 'Maternal smoking and foetal brain outcome: mechanisms and possible solutions' in Preedy, V (ed), The Neuroscience of Nicotine: Mechanisms And Treatment., Academic Press-Elsevier., New York, pp. 9-16.View/Download from: Publisher's site
Although it is well known that maternal cigarette smoke exposure (SE) is detrimental to the health of children, more than 20% of women continue to smoke during pregnancy. Children exposed to maternal smoking in utero have changes in their brain structure and size, often accompanied by cognitive defects. This may be due to increased brain oxidative stress and inflammatory response in the neonatal period, leading to neuron damage in adulthood. The mitochondria, a major source of cellular oxidative stress, are particularly vulnerable to the damage caused by the free radicals they produce. Interestingly, the female offspring seem to be protected by such adverse impact of maternal smoking. This chapter will specifically review the changes in brain inflammation and oxidative stress and the mechanism of mitophagy machinery. Potential therapeutic strategies will be suggested to mitigate the impact of maternal smoking.
Chen, H & Morris, MJ 2013, 'Mammalian target of rapamycin (mTOR): Structure, signaling pathways and biological effects' in Berhardt, LV (ed), Advances in Medicine and Biology Volume 68, Nova Science Publishers, New York, pp. 145-158.
The mammalian target of rapamycin (mTOR) is a highly conserved member of the phosphoinositide 3-kinase (PI3K) related kinase protien family and functions as a cellular sensor of changes in ambient glucose and amino acid levels; critical for cellular proliferation and differentiation. There are two multiprotein complexes of mTOR signalling components, as mTOR complex 1 (mTORC1) and mTORC2. Only mTORC1 appears to be nutrient dependent. In response to low intracellular energy availability, mTORC1 stabilizes and reduces the activity of mTOR. On the other hand, conditions of nutrient abundance promote its activity. However, such mechanisms have only been reported in either cell line models or lean animals; and hence their application to human states is yet to be determined.
Chen, H & Morris, M 2011, 'Overnutrition in Mothers and Appetite Regulators in Offspring' in Preedy, VR (ed), Handbook of Behavior, Food and Nutrition, pp. 1745-1745.View/Download from: Publisher's site
Overconsumption of energy-rich food and a sedentary lifestyle make significant contributions to the development of obesity. Over the past several decades, the proportion of people who are overweight or obese has risen sharply. As obesity becomes a global epidemic, the rate of childhood obesity is also increasing. Epidemiological and experimental evidence suggests that programming of obesity may occur following overnutrition during early development. Indeed, intrauterine factors such as abnormal glucose and lipid levels, along with hormonal changes due to maternal obesity may also be important determinants of subsequent obesity risk, even more so than genetic factors, thus contributing to the increased incidence of obesity in children. This highlights the importance of understanding the underlying mechanisms to enable better prevention and to permit development of therapeutic strategies. Over the past 5 years, the focus of research on programming of brain appetite regulation has moved from studying the impact of maternal undernutrition to that of overnutrition, as more and more women around the world enter pregnancy either overweight or obese. The appetite circuits that regulate feeding are highly conserved across mammalian species. Animal models provide an opportunity to investigate the impact of in utero or early postnatal overnutrition while controlling genetic and environmental influences. Rat offspring from mothers rendered obese by access to 'junk food' are more likely to overeat and prefer 'junk food'. They tend to develop very early (weaning age) onset lipid and glucose metabolic disorders, such as hyperlipidemia and glucose intolerance, and these last into adulthood. These offspring also manifest resistance to the anorexigenic effects of leptin. Studies in different species suggest that maternal obesity or consuming a lipid dense diet alter the key hypothalamic neuropeptides controlling food intake and energy homeostasis in offspring in utero, with aberra...
Mcalinden, KD, Chan, YL, Tan, B, Chen, H, Oliver, B, Sharma, P & Chapman, D 2017, 'MATERNAL E-CIGARETTE VAPING ENHANCES DEVELOPMENT OF ALLERGIC ASTHMA IN THE OFFSPRING', RESPIROLOGY, WILEY, pp. 104-104.
Zakarya, R, Chen, H, Brandsma, C-A, Adcock, IM & Oliver, BGG 2017, 'Epigenetic control of TGF beta induced fibrosis in COPD', EUROPEAN RESPIRATORY JOURNAL, European-Respiratory-Society (ERS) International Congress, EUROPEAN RESPIRATORY SOC JOURNALS LTD, Milan, ITALY.View/Download from: Publisher's site
Glastras, SJ, Teh, R, Tsang, M, Chen, H, Sawiris, A, Pollock, CA & Saad, S 2015, 'MATERNAL OBESITY ACCELERATES THE DEVELOPMENT OF CKD IN OFFSPRING WITH DIABETES', NEPHROLOGY, WILEY-BLACKWELL, pp. 53-53.
Glastras, SJ, Chen, H, Saad, S & Pollock, C 2014, 'GLP-1 Receptor Agonist Exendin-4 Ameliorates Oxidative Stress and Inflammation Induced By Maternal Obesity Expressed in Offspring's Kidneys', ENDOCRINE REVIEWS, ENDOCRINE SOC.
Boyce, A, Wilson, F, Chen, H, Gibson, K, Lumbers, E & Morris, M 2009, 'Differential Regulation of the Intrarenal Resin-Angiotensin System by Maternal Obesity and Postnatal Overnutrition', REPRODUCTIVE SCIENCES, 56th Annual Meeting of the Society-for-Gynecologic-Investigation, SAGE PUBLICATIONS INC, Glasgow, SCOTLAND, pp. 135A-135A.
Collaboration: A/Prof Sonia Saad (Koling), Prof Carol Pollock (Kolling), Dr Rita Machaalani (USyd), Prof Nicholas King (USyd), Dr Mehra Haghi (UTS), A/Prof Alison Ung (UTS), Prof Brian Oliver (UTS), Dr Yik Lung Chan (Woolcock); Dr Amir H Pakpour (Qazvin university of medical science, Iran), Prof Steve Bottle (QUT), Prof Weihong Li (Chengdu University of Traditional Chinese Medicine), Dr Surpon Sukjamnong (Chulalongkorn University), A/Prof Chenju Yi (Sun Yat-Sen University).