Protamine-derived peptide RPR (Arg-Pro-Arg) ameliorates oleic acid-induced lipogenesis via the PepT1 pathway in HepG2 cells.

The protamine-derived peptide RPR can ameliorate lifestyle-related diseases such as obesity and hypercholesterolemia. Thus, we hypothesized that the hypolipidemic activity of RPR could attenuate events leading to non-alcoholic fatty liver disease. Addition of 2 mM oleic acid (OA) to the culture medium induced fatty liver conditions in HepG2 cells. The OA + RPR group showed significantly decreased cellular or medium TG level compared to the OA group. SCD1 or SREBP1 protein level was significantly lower in the OA + RPR group than in the OA group. In the R + P + R amino acid mixture-treated group, the TG level was not significantly different from that in the OA-treated group. The OA + RP- or OA + PR-treated groups showed significantly decreased cellular TG level compared to the OA group. Moreover, the effect of RPR disappeared when the PepT1 was knocked down with a siRNA. Collectively, our results demonstrated that RPR effectively ameliorated hepatic steatosis in HepG2 cells via the PepT1 pathway.