Dr Hui Chen is a Senior Lecturer in the School of Life Sciences. She is the Director of High Degree Research and Director China Program, Faculty of Science. She holds an Equity Fellowship awarded by UTS and an International Young Scientist Fellowship awarded by the National Natural Science Foundation of China.
Dr Chen finished her PhD degree at The University of Melbourne (Apr 2003 - Apr 2006), where she studied brain appetite and energy metabolism regulation in two mouse models of dietary obesity and cigarette smoking. Then she took up a postdoctoral position at the University of New South Wales (Apr 2006 - Aug 2008), where she moved into a new area of research, dealing with fetal programming of early onset obesity and metabolic disorders. Dr Chen's studies focus on the impact of maternal obesity and cigarette smoking on the neural regulation of appetite and brain glucose metabolism. Dr Chen continued the same research area after she joined UTS in 2008, where her research has been extended to study maternal programming of brain disorder and kidney development, oxidative stress, mitochondrial integrity, traumatic brain injury, as well as life style management to improve metabolic disorders.
Hui's work during the past 10 years has resulted in several publications in high impact journals, including Diabetologia, Journal of Neural Chemsity, FASEB J, American Journal of Respiratory and Critical Care Medicine, Endocrinology, American Journal of Physiology, and Neuropsychopharmacology. Hui was awarded NHMRC Peter Doherty Fellowship in 2009, although this was not accepted, as it was not compatible with the UTS position.
She is a core member of the Centre of Health Technology at UTS.
Member of: Australian Neuroscience Society, International Society of Neurochemistry.
Can supervise: YES
The major aim of Dr Chen's research is dealing with fetal programming of early onset obesity and metabolic disorders using intrauterine and early postnatal intervention in mice.
Both genetic and environmental factors can contribute to obesity and gene-diet interactions are also important. Increasing evidence suggests that both maternal phenotype and nutritional state in the early postnatal phase are important in promoting brain, lung and kidney disorders, as well as type 2 diabetes in offspring. Studies carried by Dr Chen focus on the mechanism underlying the detrimental impact of long-term maternal conditions, including obesity, smoking, and e-cigarette smoking.
Interventions, such as essential amino acid supplementation and compounds are being tested to ameliorate or reverse maternal impact. Other pharmaceutical strategies will also be tested on this aspect in the future.
Major techniques used for this work include testing hormone and lipid levels in the blood by biosassays, real-time PCR, western blotting, and immunohistochemistry.
Subject coordinator for Human Pathophysiology (91239) in partnership with Sanofi Pasteur. The major project includes rasing the awareness of meningococcal disease
Teaching focuses on the physiology and pathophysiology in Gastrointestinal System, Nutrition Metabolism, Endocrine System, and Body Weight Control in Obesity.
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) . 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. TNF. 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.
Chen, H., Li, G., Chan, Y.L., Chapman, D.G., Sukjamnong, S., Nguyen, T., Annissa, T., McGrath, K.C., Sharma, P. & Oliver, B.G. 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: UTS OPUS or 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-1, IL-6, and TNF-. In adult offspring, TNF- protein levels were increased in both E-cig18 and E-cig0 groups, whereas IL-1 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.
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: UTS OPUS or 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, T., Li, G.E., Chen, H., Cranfield, C.G., McGrath, K.C. & Gorrie, C.A. 2018, 'Maternal E-Cigarette Exposure Results in Cognitive and Epigenetic Alterations in Offspring in a Mouse Model.', Chemical research in toxicology.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.
Chen, H., Li, G., Chan, Y.L., Nguyen, T., van Reyk, D., Saad, S. & G Oliver, B. 2018, 'Modulation of neural regulators of energy homeostasis, and of inflammation, in the pups of mice exposed to e-cigarettes.', Neuroscience letters.View/Download from: UTS OPUS or Publisher's site
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.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.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.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.
Glastras, S.J., Chen, H., Pollock, C.A. & 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, B.P., Glastras, S.J., Chen, H., Pollock, C.A. & 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, p. fj201800205R.View/Download from: UTS OPUS or 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.
Nguyen, L.T., 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.View/Download from: UTS OPUS or Publisher's site
Recent studies indicate that SIRT1, an important metabolic sensor and regulator of lifespan, 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 (SRT, 25mg/kg/2days i.p) or vehicle control (VEH) for 6 weeks 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, 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 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.
Saad, S., Al-Odat, I., Chan, Y.L., McGrath, K.C., Pollock, C.A., Oliver, B.G. & 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: UTS OPUS or 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-1 and TNF- 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, Y.L., Zakarya, R., Nguyen, L.T., Anwer, A.G., Zaky, A.A., Santiyanont, R., Oliver, B.G., Goldys, E., Pollock, C.A., 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, p. 6631.View/Download from: UTS OPUS or 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.
Capistrano, S.J., van Reyk, D., Chen, H. & Oliver, B.G. 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: UTS OPUS or 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.
Rahmati-Najarkolaei, F., Pakpour, A.H., Saffari, M., Hosseini, M.S., Hajizadeh, F., Chen, H. & Yekaninejad, M.S. 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.View/Download from: UTS OPUS
Prediabetic condition can lead to development of type 2 diabetes, especially in individuals who do not adhere to a healthy lifestyle. The aim of the present study was to investigate the socio-cognitive factors using the Theory of Planned Behavior (TPB) that may be associated with the choice of lifestyle in prediabetic patients.A prospective study with one-month follow up was designed to collect data from 350 individuals with prediabetic conditions. A questionnaire was used to collect the information, including demographic variables, exercise behavior, food consumption, as well as the constructs of the TPB (attitude, subjective norms, perceived behavioral control, and behavioral intention) regarding physical activity and dietary choice. The correlations between TPB variables and the dependent variables (dietary choice, physical activity) were assessed using Spearman correlation and multiple regression models.In total, 303 people participated. The mean age of the participants was 53.0 (SD 11.5) years and 42% were males. Significant correlations were found between all TPB constructs and both dependent variables (healthy eating and exercise behaviors) both at baseline and after one month (P < 0.01). The predictive validity of the TPB over time was proved for both dependent variables where past and future behaviors were significantly correlated with the constructs. Nearly 87% of the variance in exercise behavior and 72% of the variance in healthy eating behavior were explainable by TPB constructs.The TPB may be a useful model to predict behaviors of physical activity and dietary choice among prediabetic people. Therefore, it may be used to monitor lifestyle modification to prevent development of diabetes among people with prediabetic conditions.
Saffari, M., Pakpour, A.H. & 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: UTS OPUS or 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, Y.L., Saad, S., Al-Odat, I., Oliver, B.G., Pollock, C., Jones, N.M. & 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: UTS OPUS or 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, Y.L., Saad, S., Machaalani, R., Oliver, B.G., Vissel, B., Pollock, C., Jones, N.M. & 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: UTS OPUS or 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.
Glastras, S.J., Chen, H., Tsang, M., Teh, R., McGrath, R.T., Zaky, A., Chen, J., Wong, M.G., Pollock, C.A. & 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: UTS OPUS or 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, L.T., 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: UTS OPUS or 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 (pAMPK), Forkhead box FOXO3a and Peroxisome proliferator-activated receptor (PPAR) coactivator 1-alpha (PGC-1) 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.
Nguyen, L.T., 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: UTS OPUS or 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.
Sukjamnong, S., Chan, Y.L., Zakarya, R., Saad, S., Sharma, P., Santiyanont, R., Chen, H. & Oliver, B.G. 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: UTS OPUS or 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-B 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-1 and oxidative stress response nuclear factor (erythroid-derived 2)-like 2 were significantly increased in the SE offspring. Maternal MitoQ treatment normalized RAGE, IL-1, 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.
Bertrand, P.P., Polglaze, K.E., Chen, H., Sandow, S.L., Walduck, A., Jenkins, T.A., Bertrand, R.L., Lomax, A.E. & Liu, L. 2016, 'Excitability and Synaptic Transmission in the Enteric Nervous System: Does Diet Play a Role?', Advances in experimental medicine and biology, vol. 891, pp. 201-211.View/Download from: UTS OPUS or Publisher's site
Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing mechanisms to continue to process nutrients and maintain health. In particular, the enteric nervous system (ENS) needs to adapt its motor and secretory programs to deal with changes in nutrient type and load in order to optimise nutrient absorption.The nerve circuits in the gut are complex, and the numbers and types of neurons make recordings of specific cell types difficult, time-consuming, and prone to sampling errors. Nonetheless, traditional research methods like intracellular electrophysiological approaches have provided the basis for our understanding of the ENS circuitry. In particular, animal models of intestinal inflammation have shown us that we can document changes to neuronal excitability and synaptic transmission.Recent studies examining diet-induced changes to ENS programming have opted to use fast imaging techniques to reveal changes in neuron function. Advances in imaging techniques using voltage- or calcium-sensitive dyes to record neuronal activity promise to overcome many limitations inherent to electrophysiological approaches. Imaging techniques allow access to a wide range of ENS phenotypes and to the changes they undergo during dietary challenges. These sorts of studies have shown that dietary variation or obesity can change how the ENS processes information-in effect reprogramming the ENS. In this review, the data gathered from intracellular recordings will be compared with measurements made using imaging techniques in an effort to determine if the lessons learnt from inflammatory changes are relevant to the understanding of diet-induced reprogramming.
Capistrano, S.J., Zakarya, R., Chen, H. & Oliver, B.G. 2016, 'Biomass Smoke Exposure Enhances Rhinovirus-Induced Inflammation in Primary Lung Fibroblasts.', International journal of molecular sciences, vol. 17, no. 9.View/Download from: UTS OPUS or Publisher's site
Biomass smoke is one of the major air pollutants and contributors of household air pollution worldwide. More than 3 billion people use biomass fuels for cooking and heating, while other sources of exposure are from the occurrence of bushfires and occupational conditions. Persistent biomass smoke exposure has been associated with acute lower respiratory infection (ALRI) as a major environmental risk factor. Children under the age of five years are the most susceptible in developing severe ALRI, which accounts for 940,000 deaths globally. Around 90% of cases are attributed to viral infections, such as influenza, adenovirus, and rhinovirus. Although several epidemiological studies have generated substantial evidence of the association of biomass smoke and respiratory infections, the underlying mechanism is still unknown. Using an in vitro model, primary human lung fibroblasts were stimulated with biomass smoke extract (BME), specifically investigating hardwood and softwood types, and human rhinovirus-16 for 24 h. Production of pro-inflammatory mediators, such as IL-6 and IL-8, were measured via ELISA. Firstly, we found that hardwood and softwood smoke extract (1%) up-regulate IL-6 and IL-8 release (p 0.05). In addition, human rhinovirus-16 further increased biomass smoke-induced IL-8 in fibroblasts, in comparison to the two stimulatory agents alone. We also investigated the effect of biomass smoke on viral susceptibility by measuring viral load, and found no significant changes between BME exposed and non-exposed infected fibroblasts. Activated signaling pathways for IL-6 and IL-8 production by BME stimulation were examined using signaling pathway inhibitors. p38 MAPK inhibitor SB239063 significantly attenuated IL-6 and IL-8 release the most (p 0.05). This study demonstrated that biomass smoke can modulate rhinovirus-induced inflammation during infection, which can alter the severity of the disease. The mechanism by which biomass smoke exposure increases inflamm...
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: UTS OPUS or Publisher's site
Lin, C.-.Y., Chen, H. & Pakpour, A.H. 2016, 'Correlation between adherence to antiepileptic drugs and quality of life in patients with epilepsy: A longitudinal study.', Epilepsy & behavior : E&B, vol. 63, pp. 103-108.View/Download from: UTS OPUS or Publisher's site
This study aimed to investigate whether the score of self-reported medication adherence using the Medication Adherence Report Scale (MARS-5) correlates with the serum level of antiepileptic medication, as well as whether the MARS-5 score can predict the quality of life (QoL) in patients with epilepsy.A longitudinal study was carried out. The patients with epilepsy who were prescribed a minimum of one antiepileptic drug were recruited (n=807). Each participant completed a background information sheet and the MARS-5 at baseline, followed by the Liverpool Seizure Severity Scale (LSSS) and Quality of Life in Epilepsy (QOLIE-31) questionnaire at 18-month follow-up. In addition, the serum level of antiepileptic medications was measured at the follow-up.The MARS-5 score was negatively associated with the LSSS score (B=-0.089, SE=0.009, p<0.001) and positively correlated with the serum level of antiepileptic medications (B=3.200, SE=0.416, p<0.001), after adjusting for demographics and clinical characteristics. The serum level of antiepileptic drugs was significantly correlated with the overall QOLIE-31 score (B=3.118, SE=1.417, p=0.03). The MARS-5 score was significantly correlated with the overall QOLIE-31 scores and all the scores in the subcategories. In addition, the MARS-5 score was in line with the correlation between the LSSS and QOLIE-31 scores (Z=4.20, p<0.001) and between serum antiepileptic medication levels and QOLIE-31 score (Z=3.98, p<0.001).The MARS-5 score can predict the QoL in patients with epilepsy for up to 18months. Therefore, healthcare providers may predict the QoL and drug adherence using the MARS-5 score, in order to design personalized interventions.
Vivekanandarajah, A., Chan, Y.L., 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: UTS OPUS or 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 2, 3, 4, 5, 7, 9, 1 and 2 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 3, 4, 7, 9, Casp-3 and TUNEL, dorsal motor nucleus of the vagus had increased 3, 5, 7, 1 and Casp-3, nucleus of the solitary tract had increased 3 but decreased 4, 5, 1 and apoptosis, cuneate nucleus had increased 3, 2 and Casp- 3, but decreased 5, nucleus of the spinal trigeminal tract had increased 3, 7, 1, lateral reticular nucleus had decreased 1, inferior olivary nucleus had increased 1 but decreased apoptosis, and the facial had increased 2, 3 and 7. 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.
Chan, Y.L., Saad, S., Al-Odat, I., Zaky, A.A., Oliver, B., Pollock, C., Li, W., Jones, N.M. & 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: UTS OPUS or 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, Y.L., Saad, S., Pollock, C., Oliver, B., Al-Odat, I., Zaky, A.A., 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, p. 25881.View/Download from: UTS OPUS or Publisher's site
Maternal cigarette smoke exposure (SE) during gestation can cause lifelong adverse effects in the offspring's brain. Several factors may contribute including inflammation, oxidative stress and hypoxia, whose changes in the developing brain are unknown. Female Balb/c mice were exposed to cigarette smoke prior to mating, during gestation and lactation. Male offspring were studied at postnatal day (P) 1, P20 and 13 weeks (W13). SE dams had reduced inflammatory mediators (IL-1, IL-6 and toll like receptor (TLR)4 mRNA), antioxidant (manganese superoxide dismutase (MnSOD)), and increased mitochondrial activities (OXPHOS-I, III and V) and protein damage marker nitrotyrosine. Brain hypoxia-inducible factor (HIF)1 and its upstream signalling molecule early growth response factor (EGR)1 were not changed in the SE dams. In the SE offspring, brain IL-1R, IL-6 and TLR4 mRNA were increased at W13. The translocase of outer mitochondrial membrane, and MnSOD were reduced at W13 with higher nitrotyrosine staining. HIF-1 was also increased at W13, although EGR1 was only reduced at P1. In conclusion, maternal SE increased markers of hypoxia and oxidative stress with mitochondrial dysfunction and cell damage in both dams and offspring, and upregulated inflammatory markers in offspring, which may render SE dams and their offspring vulnerable to additional brain insults.
Glastras, S.J., Chen, H., McGrath, R.T., Zaky, A.A., Gill, A.J., Pollock, C.A. & Saad, S. 2016, 'Effect of GLP-1 Receptor Activation on Offspring Kidney Health in a Rat Model of Maternal Obesity.', Scientific reports, vol. 6, p. 23525.View/Download from: UTS OPUS or Publisher's site
Maternal obesity is associated with an increased risk of chronic disease in offspring, including type 2 diabetes (T2D). Exendin-4 (Exd-4) activates the glucagon like peptide-1 (GLP-1) receptor thereby decreasing serum glucose levels and body weight. In addition, Exd-4 has been shown to reduce renal and cardiac complications in experimental models of T2D. We hypothesized that treatment with Exd-4 would ameliorate the detrimental effects of maternal and diet-induced obesity on renal characteristics in offspring. Female Sprague-Dawley rats were fed either normal or high-fat diet (HFD) for 6 weeks prior to pregnancy, during pregnancy and lactation, and their offspring were weaned to normal or HFD. The offspring were randomized to Exd-4 or placebo from weaning and their kidneys harvested at Week 9. We found that the kidneys of offspring from obese mothers, regardless of postnatal diet, had significantly increased markers of inflammation, oxidative stress and fibrosis. Exd-4 ameliorated the negative renal effects of maternal obesity and in particular, reduced renal inflammation, oxidative stress and fibrosis. In conclusion, maternal obesity has persisting effects on renal structure in the offspring. GLP-1 analogues are potentially useful for protecting against the deleterious effects of maternal obesity on renal physiology in offspring.
Glastras, S.J., Chen, H., Teh, R., McGrath, R.T., Chen, J., Pollock, C.A., Wong, M.G. & Saad, S. 2016, 'Mouse Models of Diabetes, Obesity and Related Kidney Disease.', PLoS ONE, vol. 11, no. 8, pp. 1-15.View/Download from: UTS OPUS or 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, S.J., Tsang, M., Teh, R., Chen, H., McGrath, R.T., Zaky, A.A., Pollock, C.A. & Saad, S. 2016, 'Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring.', Scientific reports, vol. 6, p. 27769.View/Download from: UTS OPUS or Publisher's site
Maternal obesity is known to increase the risk of obesity and diabetes in offspring. Though diabetes is a key risk factor for the development of chronic kidney disease (CKD), the relationship between maternal obesity and CKD has not been clearly defined. In this study, a mouse model of maternal obesity was employed to determine the impact of maternal obesity on development of diabetic nephropathy in offspring. 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 diet. At postnatal Week 8, offspring were randomly administered low dose streptozotocin (STZ, 55mg/kg/day for five days) to induce diabetes. Assessment of renal damage took place at postnatal Week 32. We found that offspring of obese mothers had increased renal fibrosis, inflammation and oxidative stress. Importantly, offspring exposed to maternal obesity had increased susceptibility to renal damage when an additional insult, such as STZ-induced diabetes, was imposed. Specifically, renal inflammation and oxidative stress induced by diabetes was augmented by maternal obesity. Our findings suggest that developmental programming induced by maternal obesity has implications for renal health in offspring. Maternal obesity should be considered a risk factor for CKD.
Nguyen, L.T., Chen, H., Pollock, C.A. & 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: UTS OPUS or 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?
Chen, H., Chan, Y.L., Nguyen, L.T., Mao, Y., de Rosa, A., Beh, I.T., 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 & physiology, vol. 43, no. 11, pp. 1107-1114.View/Download from: UTS OPUS or Publisher's site
Traumatic brain injury (TBI) remains one of the leading causes of death and disability worldwide. Mild TBI may lead to neuropsychiatric sequelae, including memory loss and motor impairment. Mitochondrial dysfunction and oxidative stress have a contributory role in several neurological disorders; however, their association with mitophagy in mild TBI is unclear. TBI was induced in female Sprague Dawley (SD) rats using a New York University Impactor (10 g, impactor head 2.5 mm diameter, weight drop 50 mm) and compared to sham surgery controls. The novel object recognition and error ladder tests were performed at 24 hours and for 6 weeks post injury, and the brains were examined histologically to confirm the extent of injury. Mitochondria manganese superoxide dismutase (MnSOD) and the oxidative phosphorylation (OXPHOS) complexes I-V (CI-CV), as well as mitophagy markers, dynamin related protein 1 (DRP-1), LC3A/B and PTEN-induced putative kinase 1 (PINK-1), were measured in the penumbra by western blot. At 24 hours sham rats performed as expected on a novel object recognition test while TBI rats showed cognitive deficits at the early time points. TBI rats also showed more early motor deficits on a horizontal ladder, compared with the sham rats. MnSOD, OXPHOS CI, CIII and CV protein levels were significantly lower in the TBI group at 24 hours. DRP-1, LC3A/B I and II, and PINK-1 were increased at 6 weeks suggesting abnormal mitophagy. Moderate TBI caused immediate cognitive and mild motor functional deficits in the rats that did not persist. Reduced antioxidative capacity and possibly compromised mitochondrial function may affect the long term functional recovery.
Saffari, M., Zeidi, I.M., Fridlund, B., Chen, H. & Pakpour, A.H. 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: UTS OPUS or Publisher's site
Zabeau, L., Jensen, C.J., Seeuws, S., Venken, K., Verhee, A., Catteeuw, D., van Loo, G., Chen, H., Walder, K., Hollis, J., Foote, S., Morris, M.J., Van der Heyden, J., Peelman, F., Oldfield, B.J., Rubio, J.P., 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: UTS OPUS or Publisher's site
Chan, Y.L., Saad, S., Simar, D., Oliver, B., McGrath, K., Reyk, D.V., Bertrand, P.P., 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: UTS OPUS or 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 g/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 1 (PGC1), 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 PGC1 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...
Glastras, S.J., Wong, M.G., Chen, H., Zhang, J., Zaky, A., Pollock, C.A. & 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, p. 40.View/Download from: UTS OPUS or Publisher's site
Maternal obesity is associated with dysregulation of glucose and lipid metabolism with consequent exposure of the fetus to an abnormal metabolic milieu. It is recognized that maternal obesity predisposes offspring to chronic kidney disease (CKD). We aimed to determine whether the nuclear Farnesoid X receptor (FXR), known to play a role in maintaining homeostasis of glucose and lipid metabolism, is involved in renal injury in offspring of obese mothers.Maternal obesity was established in a rat model by feeding dams with high-fat diet prior to and during pregnancy and lactation. The offspring's kidneys were examined at postnatal Day 1and Day 20. Human kidney 2 (HK2) cells were exposed to high glucose with or without the FXR agonist GW4064 or when FXR mRNA was silenced.Glucose intolerance in the offspring of obese mothers was evident at weaning, with associated downregulation of renal FXR expression and upregulation of monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-1 (TGF-1). HK2 cells exposed to high glucose had reduced FXR expression and increased MCP-1, TGF-1, fibronectin and collagen IV expression, which was reversed in the presence of GW4064. FXR-silenced HK2 cells had amplified pro-inflammatory and pro-fibrotic markers under high glucose conditions.Maternal obesity influences renal expression of pro-inflammatory and fibrotic factors that predispose the offspring to CKD. This was associated with the downregulation of the renal FXR expression suggesting a potential protective role for FXR.
Nguyen, L.T., Stangenberg, S., Chen, H., Al-Odat, I., Chan, Y.L., Gosnell, M.E., Anwer, A.G., Goldys, E.M., Pollock, C.A. & 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: UTS OPUS or 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.
Stangenberg, S., Chen, H., Wong, M.G., Pollock, C.A. & 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: UTS OPUS or Publisher's site
The role of an adverse in utero environment in the programming of chronic kidney disease in the adult offspring is increasingly recognized. The cellular and molecular mechanisms linking the in utero environment and future disease susceptibility remain unknown. Maternal smoking is a common modifiable adverse in utero exposure, potentially associated with both mitochondrial dysfunction and epigenetic modification in the offspring. While studies are emerging that point toward a key role of mitochondrial dysfunction in acute and chronic kidney disease, it may have its origin in early development, becoming clinically apparent when secondary insults occur. Aberrant epigenetic programming may add an additional layer of complexity to orchestrate fibrogenesis in the kidney and susceptibility to chronic kidney disease in later life. In this review, we explore the evidence for mitochondrial dysfunction and epigenetic modification through aberrant DNA methylation as key mechanistic aspects of fetal programming of chronic kidney disease and discuss their potential use in diagnostics and targets for therapy.
Stangenberg, S., Nguyen, L.T., Chen, H., Al-Odat, I., Killingsworth, M.C., Gosnell, M.E., Anwer, A.G., Goldys, E.M., Pollock, C.A. & Saad, S. 2015, 'Oxidative stress, mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking.', The international journal of biochemistry & cell biology, vol. 64, pp. 81-90.View/Download from: UTS OPUS or Publisher's site
An adverse in-utero environment is increasingly recognized to predispose to chronic disease in adulthood. Maternal smoking remains the most common modifiable adverse in-utero exposure leading to low birth weight, which is strongly associated with chronic kidney disease (CKD) in later life. In order to investigate underlying mechanisms for such susceptibility, female Balb/c mice were sham or cigarette smoke-exposed (SE) for 6 weeks before mating, throughout gestation and lactation. Offspring kidneys were examined for oxidative stress, expression of mitochondrial proteins, mitochondrial structure as well as renal functional parameters on postnatal day 1, day 20 (weaning) and week 13 (adult age). From birth throughout adulthood, SE offspring had increased renal levels of mitochondrial-derived reactive oxygen species (ROS), which left a footprint on DNA with increased 8-hydroxydeoxyguanosin (8-OHdG) in kidney tubular cells. Mitochondrial structural abnormalities were seen in SE kidneys at day 1 and week 13 along with a reduction in oxidative phosphorylation (OXPHOS) proteins and activity of mitochondrial antioxidant Manganese superoxide dismutase (MnSOD). Smoke exposure also resulted in increased mitochondrial DNA copy number (day 1-week 13) and lysosome density (day 1 and week 13). The appearance of mitochondrial defects preceded the onset of albuminuria at week 13. Thus, mitochondrial damage caused by maternal smoking may play an important role in development of CKD at adult life.
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: UTS OPUS or 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: UTS OPUS or 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.
Saffari, M., Pakpour, A.H., 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, A.H., 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.View/Download from: UTS OPUS
Zeidi, I., Saffari, M., Chen, H. & Pakpour, A.H. 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: UTS OPUS or 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: UTS OPUS or 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- 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: UTS OPUS or 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., Simar, D., Pegg, K., Saad, S., Palmer, C. & Morris, M.J. 2014, 'Exendin-4 is effective against metabolic disorders induced by intrauterine and postnatal overnutrition in rodents', Diabetologia, vol. 57, no. 3.View/Download from: UTS OPUS or 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 g/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.
Chen, H., Dorrigan, A., Saad, S., Hare, D.J., Cortie, M.B. & 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: UTS OPUS or 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.
Grayson, T.H., Chadha, P.S., Bertrand, P.P., Chen, H., Morris, M.J., Senadheera, S., Murphy, T.V. & Sandow, S.L. 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: UTS OPUS or 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, J.U., Langenbach, S.Y., Vlahos, R., Gualano, R.C., Morris, M. & Anderson, G.P. 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: UTS OPUS or 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, M.J. 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: UTS OPUS or 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 11-hydroxysteroid dehydrogenase type 1 were reduced by exercise in HHEX (vs HH; P < 0.05).
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: UTS OPUS or 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.
Cortie, M.B., Al Hafed, E., Chen, H., Valenzuela, S., Ting, S., Sonvico, F. & Milthorpe, B.K. 2013, 'Nanomedical research in Australia and New Zealand', Nanomedicine, vol. 8, no. 12, pp. 1999-2006.View/Download from: UTS OPUS or 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, R.L., Senadheera, S., Tanoto, A., Tan, K.L., Howitt, L., Chen, H., Murphy, T.V., Sandow, S.L., Liu, L. & Bertrand, P.P. 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: UTS OPUS or Publisher's site
Constipation and slowed transit are associated with diet-induced obesity, although the mechanisms by which this occurs are unclear. Enterochromaffin (EC) cells within the intestinal epithelium respond to mechanical stimulation with the release of serotonin [5-hydroxytryptamine (5-HT)], which promotes transit. Thus our aim was to characterize 5-HT availability in the rat colon of a physiologically relevant model of diet-induced obesity. EC cell numbers were determined immunohistochemically in chow-fed (CF) and Western diet-fed (WD) rats, while electrochemical methods were used to measure mechanically evoked (peak) and steady-state (SS) 5-HT levels. Fluoxetine was used to block the 5-HT reuptake transporter (SERT), and the levels of mRNA for tryptophan hydroxylase 1 and SERT were determined by quantitative PCR, and SERT protein was determined by Western blot. In WD rats, there was a significant decrease in the total number of EC cells per crypt (0.86 ± 0.06 and 0.71 ± 0.05 in CF and WD, respectively), which was supported by a reduction in the levels of 5-HT in WD rats (2.9 ± 1.0 and 10.5 ± 2.6 M at SS and peak, respectively) compared with CF rats (7.3 ± 0.4 and 18.4 ± 3.4 M at SS and peak, respectively). SERT-dependent uptake of 5-HT was unchanged, which was supported by a lack of change in SERT protein levels. In WD rats, there was no change in tryptophan hydroxylase 1 mRNA but an increase in SERT mRNA. In conclusion, our data show that foods typical of a WD are associated with decreased 5-HT availability in rat colon. Decreased 5-HT availability is driven primarily by a reduction in the numbers and/or 5-HT content of EC cells, which are likely to be associated with decreased intestinal motility in vivo.
Chen, H., Simar, D., Ting, H.J., Erkelens, J.R. & Morris, M.J. 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: UTS OPUS or 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, M.J. 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: UTS OPUS or 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.
Chen, H., Saad, S., Sandow, S.L. & Bertrand, P.P. 2012, 'Cigarette smoking and brain regulation of energy homeostasis', Frontiers in Pharmacology, vol. 3, no. 147, pp. 1-8.View/Download from: UTS OPUS or 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., Saad, S., Sandow, S.L. & Bertrand, P.P. 2012, 'Cigarette smoking and brain regulation of energy homeostasis.', Frontiers in pharmacology, vol. 3, p. 147.View/Download from: UTS OPUS or 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 mother's metabolic system and is a significant contributor to adverse pregnancy outcomes. Smoking is a predictor of future risk for respiratory dysfunction, social behavioral problems, cardiovascular disease, obesity, and type-2 diabetes. Catch-up growth is normally observed in children exposed to intrauterine smoke, which has been linked to subsequent childhood obesity. Nicotine can have a profound impact on the developing fetal brain, via its ability to rapidly and fully pass the placenta. In animal studies this has been linked with abnormal hypothalamic gene expression of appetite regulators such as downregulation of NPY and POMC in the arcuate nucleus of the hypothalamus. Maternal smoking or nicotine replacement leads to unhealthy eating habits (such as junk food addiction) and other behavioral disorders in the offspring.
Bertrand, R.L., Senadheera, S., Markus, I., Liu, L., Howitt, L., Chen, H., Murphy, T.V., Sandow, S.L. & Bertrand, P.P. 2011, 'A Western diet increases serotonin availability in rat small intestine', No Code, vol. 152, no. 1, pp. 36-47.View/Download from: UTS OPUS or 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: UTS OPUS or 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, M.A., 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: UTS OPUS or 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, A.H., 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: UTS OPUS or 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, J.M. 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: UTS OPUS or 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. & Morris, M. 2009, 'Differential responses of orexigenic neuropeptides to fasting in offspring of obese mothers', Obesity, vol. 17, no. 7, pp. 1356-1362.View/Download from: UTS OPUS or Publisher's site
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., Li, K. & Shan, Z.H. 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.
Chen, H., Simar, D. & Margaret, J.M. 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: UTS OPUS or 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: UTS OPUS or 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, M.J. 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: UTS OPUS or 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, J.E., 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: UTS OPUS or 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: UTS OPUS or 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, M.J., 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: UTS OPUS or 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.
Chen, H. & Morris, M. 2007, 'Maternal smoking - a contributor to the obesity epidemic?', Obesity Research & Clinical Practice, vol. 1, no. 3, pp. 155-163.View/Download from: UTS OPUS or Publisher's site
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, J.E., 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: UTS OPUS or 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, J.E., 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: UTS OPUS or 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, J.E., 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: UTS OPUS or 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: UTS OPUS or 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, J.E., Anderson, G. & Margaret, J.M. 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: UTS OPUS or 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, Q., Fan, K. & Chen, H. 2000, 'Localized amyloidosis of cervical lymph nodes.', Chinese medical journal, vol. 113, no. 2, pp. 184-185.
Chen, H. & Morris, M.J. 2013, 'Mammalian target of rapamycin (mTOR): Structure, signaling pathways and biological effects' in Berhardt, L.V. (ed), Advances in Medicine and Biology Volume 68, Nova Science Publishers, New York, pp. 145-158.View/Download from: UTS OPUS
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, V.R. (ed), Handbook of Behavior, Food and Nutrition, pp. 1745-1745.View/Download from: UTS OPUS or 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, K., Chan, Y., Kota, A., Chen, H., Oliver, B. & Sharma, P. 2017, 'Maternal E-cigarette Vaping Enhances Development of Allergic Asthma In the Offspring', American Journal of Respiratory and Critical Care Medicine, American Thoracic Society.View/Download from: UTS OPUS
Rationale: E-cigarettes (eCig) are being considered as an alternative to quit cigarette smoking (CS) while their long-term safety and effect on lung patho-physiology are not known. Maternal eCig-vaping may be considered as a safer CS-replacement during pregnancy. Thus the effect of maternal eCig vaping needs further assessment, particularly the effect this has on offspring and development of allergic asthma later in life. Combining mouse models of maternal vaping and allergic asthma and human airway smooth muscle cells (ASM) in vitro we tested whether maternal eCig vaping enhances features of allergic asthma in the offspring.
Methods: Female BALB/c mice were vaped with either eCig vapour (± nicotine) or CS+eCig (+nicotine) or room air (control group). The eCig vaping was started prior to mating and continued during gestation and lactation while CS-exposure was used prior to mating and replaced with eCig during gestation and mating. The female offspring from these mothers were subjected to an ovalbumin (OVA)-induced allergic asthma model. 24 hours after the last aerosolized OVA or saline challenge, lung function measurements were performed using flexiVent (Scireq, Canada) to increasing concentration of methacholine (MCh). Airway inflammation was assessed by counting total immune cell influx in BAL fluid. Human ASM cells were treated with varying concentrations of eCig liquid condensate and key parameters of mitochondrial function were measured with a Seahorse XF analyzer.
Results: Repeated allergen-exposure induced Th2-driven inflammation in OVA-exposed mice, characterized by massive influx of leukocytes predominantly eosinophils (OVA: 3x105±8.3x104 vs Saline: 1.1x102±1x102) and to some extent neutrophils (OVA: 1.3x104±4.4x103 vs Saline: 1.3x102±1.1x102) into the airways. The effect of allergen on airway eosinophilia was significantly enhanced in the offsprings from eCig OVA (+Nic)-exposed mothers when compared with eCig OVA (-Nic) or CS+eCig animals. OVA-exposed ...
Zakarya, R., Chen, H., Brandsma, C.-.A., Adcock, I.M. & Oliver, B.G.G. 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
Collaboration: Dr Sonia Saad (Koling), Prof Carol Pollock (Kolling), Dr Paul Bertrand (RMIT); Dr Nicole Jones (UNSW); Dr Amir H Pakpour (Qazvin university of medical science, Iran), Prof Steve Bottle (QUT).