Anti-Obesity and Hypocholesterolemic Actions of Protamine-Derived Peptide RPR (Arg-Pro-Arg) and Protamine in High-Fat Diet-Induced C57BL/6J Mice

Dietary protamine can ameliorate hyperlipidemia; however, the protamine-derived active peptide and its hypolipidemic mechanism of action are unclear. Here, we report the discovery of a novel anti-obesity and hypocholesterolemic peptide, RPR (Arg-Pro-Arg), derived from protamine in mice fed a high-fat diet for 50 days. Serum cholesterol levels were significantly lower in the protamine and RPR groups than in the control group. White adipose tissue weight was significantly decreased in the protamine and RPR groups. The fecal excretion of cholesterol and bile acid was significantly higher in the protamine and RPR groups than in the control group. We also observed a significant decrease in the expression of hepatic SCD1, SREBP1, and adipocyte FAS mRNA, and significantly increased expression of hepatic PPAR alpha and adipocyte PPAR gamma 1 mRNA in the protamine group. These findings demonstrate that the anti-obesity effects of protamine are linked to the upregulation of adipocyte PPAR gamma 1 and hepatic PPAR alpha and the downregulation of hepatic SCD1 via SREBP1 and adipocyte FAS. RPR derived from protamine has a crucial role in the anti-obesity action of protamine by evaluating the effective dose of adipose tissue weight loss.

Automated summary

The study reported a novel anti-obesity and hypocholesterolemic peptide, RPR, derived from protamine in mice fed a high-fat diet. Results showed that protamine and RPR can lower serum cholesterol levels, decrease white adipose tissue weight, and increase fecal excretion of cholesterol and bile acid.