Fibroblast growth factor 19 treatment ameliorates disruption of hepatic lipid metabolism in farnesoid X receptor (Fxr)-null mice

Abstract

Human fibroblast growth factor 19 (FGF19) is an enterohepatic hormone that is involved in the regulation of hepatic metabolism of bile acids, lipids, and glucose. Farnesoid X receptor (Fxr)-null mice exhibit steatosis-like symptoms, showing higher hepatic lipid levels than with the wild-type mice. We investigated the influence of FGF19 treatment on hepatic lipogenesis in Fxr-null mice. Recombinant FGF19 treatment (400 μg/kg/d) for 3 d prevented the accumulation of lipid droplets and decreased serum alanine aminotransferase activity and hepatic lipid levels, including those of triglycerides and free fatty acids. The treatment significantly decreased the hepatic mRNA levels of acetyl-CoA carboxylase 1 (Acc1), Cd36, and sterol regulatory element-binding protein-1c (Srebp-1c) as well as those of acetyl-CoA carboxylase 2 (Acc2), stearoyl CoA desaturase 1 (Scd1), and Cyp7a1. FGF19 treatment (4 μg/kg/d) for 3 d also decreased the hepatic free fatty acid levels and mRNA levels of Acc1, Cd36, and Srebp-1c. These results indicate that FGF19-mediated signaling ameliorates disrupted hepatic lipogenesis in Fxr-null mice. © 2011 Pharmaceutical Society of Japan.