Hepatic Carbohydrate And Lipid Metabolism Are Altered In Rats Fed Creatine-Supplemented Diets

Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver damage. Insulin resistance often accompanies NAFLD and these phenomena are hallmarks of the metabolic syndrome. Recently, we reported that creatine supplementation prevents hepatic steatosis, lipid peroxidation and insulin resistance in rats fed a high-fat diet. In order to examine potential mechanisms underlying these observations, we used McArdle RH-7777 rat hepatoma cells treated with oleic acid as a model of hepatocyte lipid accumulation. We found that cells cultures with creatine had a dose dependent reduction in cellular TG accumulation. Using radiolabeled tracers we have demonstrated that incubation of hepatoma cells with creatine increases fatty acid oxidation and decreases both fatty acid and TG synthesis. In-line with increased fatty acid oxidation, analysis of mRNA from hepatoma cells treated with creatine had increased expression of PPARα and its targets CPT1a and LCAD. We have also found that creatine treated hepat...