RESUMEN
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 PPARα and adipocyte PPARγ1 mRNA in the protamine group. These findings demonstrate that the anti-obesity effects of protamine are linked to the upregulation of adipocyte PPARγ1 and hepatic PPARα 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.
Asunto(s)
Tejido Adiposo Blanco/efectos de los fármacos , Fármacos Antiobesidad/farmacología , Anticolesterolemiantes/farmacología , Colesterol/sangre , Obesidad/tratamiento farmacológico , Oligopéptidos/farmacología , Protaminas/farmacología , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/fisiopatología , Adiposidad/efectos de los fármacos , Animales , Biomarcadores/sangre , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Acido Graso Sintasa Tipo I/genética , Acido Graso Sintasa Tipo I/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Obesidad/genética , Obesidad/metabolismo , Obesidad/fisiopatología , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Estearoil-CoA Desaturasa/genética , Estearoil-CoA Desaturasa/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Pérdida de Peso/efectos de los fármacosRESUMEN
In this study, ß-conglycinin (100 mg/kg) was orally administered to Wistar rats in order to identify peptides that may be derived from the protein in the blood. Plasma samples taken from the tail vein up to 8 h after administration were analyzed by matrix-assisted laser desorption/ionization (MALDI) and liquid chromatography-time-of-flight (LC-TOF) mass spectrometry (MS). In total, 126 signals were detected by MALDI-MS. Among the signals, nine oligopeptides (SEL, KGPL, SILGA, DSEL, GDANI, SYFV, CLQSC, GEQPRPF, and LVINEGDA) were successfully identified as ß-conglycinin-derived peptides by LC-TOF/MS at a plasma concentration of 0.75-756 pmol/mL. The results demonstrated that ß-conglycinin could be the dietary source protein for the oligopeptides produced prior to entering the circulating bloodstream of rats.