engleski

Glucose dysregulation in obesity: studies in rats with constitutionally altered serotonin homeostasis

Introduction: Obesity is a major worldwide problem today. It is defined as an abnormal or excessive fat accumulation that presents a risk to health. Obesity is commonly associated with disturbed glucose metabolism, a condition implicated in the pathogenesis of chronic illnesses such as type II diabetes and Alzheimer's disease. Molecular mechanisms of glucose dysregulation in obesity are yet poorly understood. The Wistar- Zagreb 5HT rat is an animal model developed by the use of selective breeding toward extremes of platelet serotonin (5HT) parameters. Animals from high-5HT and low-5HT subline of the WZ-5HT rat model have constitutionally upregulated and downregulated, respectively, 5HT activity. In addition, high-5HT rats exhibit a lifelong increased body weight and elevated adiposity as compared to low-5HT animals. Here we explored glucose tolerance status in animals from the WZ-5HT sublines. In order to shed some light on the molecular pathways underlying the observed metabolic differences between high-5HT and low- 5HT animals, we further analysed them for the hypothalamic expression of the three selected insulin signalling associated genes. Methods: Glucose homeostasis was assessed by performing glucose tolerance test (GTT) using tail incision method. Reverse transcription - quantitative polymerase chain reaction (RT-qPCR) based on SyberGreen technology was used to assess hypothalamic expression of the insulin receptor (Insr), insulin substrate 1 (Irs1) and 2 (Irs2) genes. Results: Rats from the high-5HT subline demonstrated significantly higher baseline (fasting) glucose levels as well as increased glucose levels at all time points following i.p. glucose administration, as compared to animals from the low-5HT subline. No significant differences between the sublines were observed in the hypothalamic expression of Insr, Irs1 and Irs2 genes. Conclusion: Our results obtained on an original rodent model indicate a link between endogenous 5HT tone, obesity and disturbances in glucose metabolism. Further studies are needed to clarify molecular pathways underlying the observed metabolic differences between the WZ-5HT sublines.

obesity ; glucose tolerance ; serotonin ; hypothalamus ; Wistar-Zagreb 5HT rats

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