The (pro)renin receptor blocker peptide effects on regulation of body weight and glucose homeostasis in mice with diet‐induced obesity (1101.10)

Abstract

Introduction. The Prorenin receptor [(P)RR] is a recently discovered member of the renin‐angiotensin system (RAS). Adipose tissue (AT) is a 2nd major source of circulating angiotensinogen during obesity and (P)RR effects in adipose tissue have not been clearly identified yet. In this study, we investigated the relationship between (P)RR and body weight (BW) and expression of gene and proteins in the insulin signaling pathway in AT.Material and methods. 12 week‐old C57BL/6 male mice were placed on a high‐fat/high‐carbohydrate (HF/HC) or normal diet (ND) and treated with a (P)RR blocker [(P)RR‐B] or saline for 10 weeks. BW and food intake was assessed weekly. At the end of treatment, mice were euthanized, plasma was collected for the measurement of glucose (G) and insulin (I); AT were separated, weighed and flash frozen. The GLUTs gene expressions were measured by q‐PCR; PKB proteins detected by Western‐Blot.Results.(P)RR‐B administration lowered BW in mice on HF/HC as a result of lower body fat mass. Circulating levels of G,I and the G/I ratio were lowered by the (P)RR‐B on both diet. The GLUTs gene expression in AT was affected by HF/HC and improved with (P)RR‐B administration. Moreover, the PKB phosphorylation in AT was affected with HF/HC, where (P)RR‐B administration improve PKB phosphorylation in both diet.Conclusion. The pharmacologic blockade of the (P)RR lowered BW in mice on a HF/HC, improved glucose homeostasis potentially by improving GLUTs gene expression profile and PKB phosphorylation in AT.Grant Funding Source: Supported by CDA, MDRC