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.
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 obesewomen 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 obesemice 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 obesemice. 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.
Authors: Steven J Forrester; George W Booz; Curt D Sigmund; Thomas M Coffman; Tatsuo Kawai; Victor Rizzo; Rosario Scalia; Satoru Eguchi Journal: Physiol Rev Date: 2018-07-01 Impact factor: 37.312
Authors: Eva Gatineau; Gertrude Arthur; Audrey Poupeau; Kellea Nichols; Brett T Spear; Nathan R Shelman; Gregory A Graf; Ryan E Temel; Frédérique B Yiannikouris Journal: Am J Physiol Endocrinol Metab Date: 2021-01-18 Impact factor: 4.310