Obesity Human Soluble Prorenin Receptor Expressed in Adipose Tissue Improves Insulin Sensitivity and Endothelial Function in Obese Female Mice.

Abstract

Soluble prorenin receptor (sPRR) is a component of the renin-angiotensin system (RAS) identified as a plasma biomarker for human metabolic disease. However, what tissue source of sPRR is implicated in the modulation of metabolic function remains unclear. This study investigated the contribution of human sPRR (HsPRR) produced in the adipose tissue (Adi) on the metabolic and cardiovascular function of lean and obese male and female mice. Adi-HsPRR mice, generated by crossing human sPRR-Myc-tag and Adiponectin/Cre mice, were fed a low-fat or high-fat diet (10% and 60% kCal from fat, respectively) for 20 weeks. Obese Adi-HsPRR mice showed elevated sPRR levels in adipose tissue without affecting adipocyte size or fat depot weight. Despite plasma sPRR being similar between obese Adi-HsPRR and control female mice, a positive correlation between plasma sPRR and adiposity was present only in controls. Obese Adi-HsPRR male mice showed elevated plasma sPRR compared with controls, but no correlation with adiposity was found in either group. Nevertheless, Adi-HsPRR expression improved insulin sensitivity and endothelial function, reduced adipogenic genes mRNA abundance (PPARg, SEBP1C and CD36), and increased plasma Angiotensin 1-7 levels only in obese HsPPR female mice. Taken together, elevated HsPRR in adipose tissue improved metabolic and vascular function in obese female mice despite normal circulating levels of sPRR, whereas increased local and circulating levels of HsPRR did not influence metabolic and cardiovascular function in obese male mice. Our data suggest that increased plasma sPRR associated with metabolic disease could be produced by other tissues rather than adipocytes.