Key result
The (P)RR blocker HRP reduced weight gain by 20% and visceral fat by 19% in obese mice, while (P)RR mRNA was increased by 33% in the fat of insulin-resistant versus insulin-sensitive obese women.
Why the study?
Does handle region peptide (HRP) reduce weight gain and improve cardiometabolic risk factors in mice on a high-fat/high-carbohydrate diet?
Does handle region peptide (HRP) reduce weight gain and improve cardiometabolic risk factors in mice on a high-fat/high-carbohydrate diet?
Blocking the prorenin/renin receptor reduces weight gain and improves the metabolic profile in obese mice, suggesting it as a potential novel therapeutic target for obesity.
Hypothesis-generating in obese mice; clinical trials needed before considering (P)RR blockade for obesity.
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.
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Tan et al. (2014) studied Obesity. Handle region peptide (HRP) / (P)RR blocker vs. Saline (mice) / Insulin-sensitive obese women (humans) was evaluated on Weight gain, visceral fat, and (P)RR mRNA expression. The (P)RR blocker HRP reduced weight gain by 20% and visceral fat by 19% in obese mice, while (P)RR mRNA was increased by 33% in the fat of insulin-resistant versus insulin-sensitive obese women.
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