Effects of sleeve gastrectomy on lipid and energy metabolism in ZDF rats via PI3K/AKT pathway

Am J Transl Res. 2018 Nov 15;10(11):3713-3722. eCollection 2018.

Abstract

Sleeve Gastrectomy (SG), as the most effective bariatric surgery, has been using to chronically lose weight and control glucose metabolism in Type 2 diabetes mellitus patients. However, the underlining mechanism is still unclear. In this study, we performed SG on Zucker diabetes fatty (ZDF) rat and investigated visceral lipid metabolism and energy metabolism. After performance of SG, weight, food intake, fasting plasma glucose (FPG) and oral glucose tolerance teat (OGTT) of rats were measured. Furthermore, whole-body metabolic parameters were obtained through TSE LabMaster. Blood lipid and renal function were analyzed by serum from rats' tail vein. Furthermore, the renal genes expression was either detected by real-time PCR, while western blotting was employed to detect the AKT/PI3K proteins level in rats' kidney. Compared to control groups, body weight of ZDF rats treated with SG were significantly reduced, simultaneously with glucose homeostasis and energy metabolism improved including RER (P<0.05), energy expenditure (P<0.05) at night and activity of animal. Meanwhile, serum lipid of ZDF rats after SG was decreased, and renal function recovered. Histology analysis confirmed that the size of perirenal adipose from SD treated ZDF rats obviously decreased (P<0.001), effectively stimulating up-regulation of lipogenesis genes (P<0.05), while adipogenesis genes (P<0.05) in kidney was down-regulated. In addition, phosphorylation of PI3K (p-PI3K) and AKT (p-AKT) in rats kidney were significantly decreased in SG group (P<0.05). Weight loss, food intake, fasting plasma glucose and glucose tolerance in SG surgery rats were improved, which were coincident with energy metabolism changes. In conclusion, SG improves lipid and energy metabolism in ZDF rats model due to activating PI3K/Akt signaling pathway, which was contributed to the mechanism of bariatric surgery toward kidney.

Keywords: PI3K/Akt pathway; Sleeve gastrectomy; Zucker diabetes fatty rats; energy metabolism; lipid metabolism.