Project description:Gene expression profiles in tissues of Zucker diabetic fatty (ZDF) rats compared with age matched Zucker lean control (ZLC) rats. Keywords: other
Project description:Population based studies have established that androgen deficiency in males correlates with type 2 diabetes, visceral adiposity, and metabolic syndrome. Androgen therapy has been investigated as a possible treatment regime to combat these disorders. However, the molecular mechanism of androgen effects on these diseases still remain poorly understood. The zucker diabetic fatty (ZDF) rat, containing a mutation in the leptin receptor, is a well-investigated model of obesity and type 2 diabetes. Male rats are characterized as androgen deficient and spontaneously develop obese, hyperlipidemia, hyperglycemia and hyperinsulinemia. In this study, we used ZDF male rats as a model of metabolic syndrome to investigate the effects of testosterone administration on the development of the metabolic conditions. Methods: Male ZDF rats at six week of age were randomly divided into two groups and administered testosterone undecanoate(TU) or vehicle alone every three days for three weeks. After three weeks, overnight fasted blood glucose and insulin concentrations were significantly higher and glucose tolerance and insulin sensitivity were impaired in TU treated ZDF rats compared to vehicle controls. Moreover, increased serum triglycerides and VLDL were observed in TU treated rats. To further explore the observed metabolic changes in TU treated ZDF rats, whole-genome microarray analysis were performed on isolated liver mRNA. Results: Array analysis revealed that many hepatic lipogenic genes were increased in male ZDF rat livers treated with TU. Interestingly, SREBP-1c, a key transcriptional activator of lipogenic genes and PGC-1 , an activator of SREBP-1c were induced while small heterodimer partner, a transcriptional inhibitor of lipogenic genes was suppressed by TU treatment. Exploring signaling pathways for these effects, we observed that the hepatic activated forms of STAT3 and AMPK, two known inhibitors of hepatic lipogenesis, were decreased in TU treated rat. Moreover, we observed that DHT could block the induction of STAT3 and AMPK phosphorylation in treated primary human hepatocytes. Preliminarily, in the leptin receptor positive zucker diabetic lean male rats, we observed that TU treatment has an oppose effect on the hepatic lipogenic genes, suggesting that hepatic leptin signaling may influence androgen signaling. Further insight into the relationship between androgen deficiency and the leptin system may help improve treatment of the metabolic syndrome. Population based studies have established that androgen deficiency in males correlates with type 2 diabetes, visceral adiposity, and metabolic syndrome. Androgen therapy has been investigated as a possible treatment regime to combat these disorders. However, the molecular mechanism of androgen effects on these diseases still remain poorly understood. The zucker diabetic fatty (ZDF) rat, containing a mutation in the leptin receptor, is a well-investigated model of obesity and type 2 diabetes. Male rats are characterized as androgen deficient and spontaneously develop obese, hyperlipidemia, hyperglycemia and hyperinsulinemia. In this study, we used ZDF male rats as a model of metabolic syndrome to investigate the effects of testosterone administration on the development of the metabolic conditions. Two-condition experiment. (1) lean ZDF rats (control) vs. lean ZDF rats (testosterone treated). (2) obese ZDF rats (control) vs. obese ZDF rats (testosterone treated). Biological replicates: 4 control replicates, 4 treated replicates.
Project description:In this study we have analyzed gene expression and metabolite levels in the livers of male and female Zucker diabetic fatty (ZDF) rats. We speculated that the sex different development of diabetes in the ZDF animals presents the opportunity to relate gender to diabetes (since only males become diabetic on normal diet). In this model one can search for parameters that distinguish females fed normal diet compared to high fat diet (i.e. components that vary with the development of diabetes) and evaluate if such changes can be related to components that characterize male diabetic animals.. Biological replicates: 4 ZDF female rat livers from rats on a standard diet (SD) and 4 ZDF female rat livers from rats on high-fat diet (HFD) (6 weeks). One replicate per array. Hepatic gene expression, hepatic metabolites, sex-differences
Project description:In this study we have analyzed gene expression and metabolite levels in the livers of male and female Zucker diabetic fatty (ZDF) rats. We speculated that the sex different development of diabetes in the ZDF animals presents the opportunity to relate gender to diabetes (since only males become diabetic on normal diet). In this model one can search for parameters that distinguish females fed normal diet compared to high fat diet (i.e. components that vary with the development of diabetes) and evaluate if such changes can be related to components that characterize male diabetic animals.. Biological replicates: 4 male ZDF rat livers from rats on a standard diet (SD) and 4 ZDF female rat livers from rats on a standard diet (SD). One replicate per array. Hepatic gene expression, hepatic metabolites, sex-differences
Project description:In this study we have analyzed gene expression and metabolite levels in the livers of male and female Zucker diabetic fatty (ZDF) rats. We speculated that the sex different development of diabetes in the ZDF animals presents the opportunity to relate gender to diabetes (since only males become diabetic on normal diet). In this model one can search for parameters that distinguish females fed normal diet compared to high fat diet (i.e. components that vary with the development of diabetes) and evaluate if such changes can be related to components that characterize male diabetic animals..
Project description:In this study we have analyzed gene expression and metabolite levels in the livers of male and female Zucker diabetic fatty (ZDF) rats. We speculated that the sex different development of diabetes in the ZDF animals presents the opportunity to relate gender to diabetes (since only males become diabetic on normal diet). In this model one can search for parameters that distinguish females fed normal diet compared to high fat diet (i.e. components that vary with the development of diabetes) and evaluate if such changes can be related to components that characterize male diabetic animals..
Project description:Here we analyzed how whole egg consumption in Zucker Diabetic Fatty (ZDF) rats alters microRNA and mRNA expression across the adipose, liver, kidney, and prefrontal cortex tissue. Male ZDF (fa/fa) rats (n = 12) and their lean controls (fa/+) (n = 12) were obtained at 6 wk of age. Rats had ad libitum access to water and were randomly assigned to a modified semi-purified AIN93G casein-based diet or a whole egg-based diet, both providing 20% protein (w/w). TotalRNA libraries were prepared using QuantSeq 3' mRNA-Seq and Lexogen smallRNA library prep kits and were further sequenced on an Illumina HighSeq3000. Differential gene expression was conducted using DESeq2 in R and Benjamini-Hochberg adjusted P- values controlling for false discovery rate at 5%.We identified 9 microRNAs and 583 genes that were differentially expressed in response to 8 wk of consuming whole egg-based diets.