Impact of the prorenin/renin receptor on the development of obesity and associated cardiometabolic risk factors

Autor: Paul Tan, Catherine Michel, Thi M.-D. Nguyen, Peter W. Schiller, Rémi Rabasa-Lhoret, Sandra Bisotto, Julie L. Lavoie, Zulaykho Shamansurova, Jolanta Gutkowska, Marie-Soleil Gauthier
Rok vydání: 2014
Předmět:
Zdroj: Obesity. 22:2201-2209
ISSN: 1930-7381
DOI: 10.1002/oby.20844
Popis: Objective Obesity is a worldwide epidemic and current treatments have limited success thus, novel therapies are warranted. Our objective was to determine whether the prorenin/renin receptor [(P)RR] is implicated in obesity. Methods Mice received a normal or high-fat/high-carbohydrate diet with the handle region peptide (HRP), a (P)RR blocker, or saline for 10 weeks. Post-menopausal non-diabetic obese women were enrolled in the Complication Associated with Obesity Study and were classified as insulin-resistant (IRO) or -sensitive (ISO) using a hyperinsulinemic-euglycemic clamp. Results In mice, obesity increased the (P)RR by twofold in adipose tissue. Likewise, renin increased by at least twofold. The HRP reduced weight gain in obese mice by 20% associated to a 19% decrease in visceral fat. This was accompanied by a 48% decrease in leptin mRNA in fat and 33% decrease in circulating leptin. Inflammatory markers were also decreased by the HRP treatment. HRP normalized triglyceridemia and reduced insulinemia by 34% in obese mice. Interestingly, we observed a 33% increase in (P)RR mRNA in the fat of IRO women compared to ISO. Conclusions This is the first report of a potential implication in obesity of the (P)RR which may be a novel therapeutic target.
Databáze: OpenAIRE
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