Obese Zucker Rats after experiencing a Roux-en-Y gastric bypass surgery or calorie restriction: An expression study in the heart and various brain regions

Introduction Obesity, which is associated with several comorbidities like diabetes type 2, cardiovascular disease and dementia, represents a major health burden. While conservative treatments often fail to improve, bariatric surgery is an effective weight-loss procedure. Although its positive effect is incompletely understood, hormonal and neuroendocrine changes are suggested to be causative.

Methods The “Wuerzburg Adipose Rodent Study” (WARS) uses the (fa/fa) Zucker rat as an animal model for obesity to study the effects of bariatric surgery (Roux-en-Y gastric bypass, RYGB) and calorie restriction on obesity and cardiac function. The study design comprises four experimental groups: Zucker lean rats sham treated; Zucker rats sham treated, Zucker rats RYGB treated, and Zucker rats sham treated with a calorie reduced diet. Applying an insulin signaling pathway RT2 profiler PCR array revealed expression differences of some of these investigated genes [such as insulin-like growth factor (Igf)1] in heart tissue of rats of different treatment groups of this study.

Results To investigate gene expression alterations of insulin signaling pathway-related genes in the brain of these rats, we performed quantitative real time PCRs (qPCR) using RNA extracted from hypothalamus, hippocampus, prefrontal cortex and striatum. Heart RNA was used as an additional control and to verify the originally obtained results.

Conclusion We detected significantly decreased expression levels of Irs1, Igf1 and Insr in the heart of Zucker rats compared to Lean rats. RYGB and calorie restriction do not seem to have the potential to reverse effect. In the brain, only Akt2 expression was increased in obese rats compared to lean controls. However, the investigation of other energy homeostasis-related genes like the adiponectin receptor 1 are still ongoing.