Creatine Supplementation may prevent NAFLD by stimulating fatty acid oxidation

Abstract

Creatine is a naturally occurring metabolite responsible for maintaining ATP levels in tissues with high and rapidly fluctuating energy demands. Recently, we reported the novel and surprising finding that dietary creatine supplementation prevents hepatic steatosis in rats fed a high‐fat diet. The primary goal of this project is to investigate the mechanism by which creatine influences hepatic lipid metabolism. To accomplish this goal we incubated McArdle RH‐7777 hepatoma cells with oleic acid (OA) and creatine. We found that creatine reduces cellular TG levels by 50% (P<0.05). Incorporation of 3H‐oleate into TG was reduced by creatine by 40% (P<0.05). Creatine supplementation resulted in a 2‐fold increase (P<0.05) in 14CO2 production from 14C‐oleate, and a 20% increase (P<0.05) in levels of the ketone body, â‐hydroxybutyrate. To determine whether dietary creatine supplementation can improve liver function in mice susceptible to NAFLD, we fed the liver‐specific CTP:phosphocholine cytidylyltransferase‐α knockout (LCTαKO) and control mice a HFD with or without 1% creatine. After 3 weeks of feeding, creatine supplementation prevented the 3‐fold increase (P<0.05) in hepatic TG in the LCTαKO mice. The data suggests that creatine may be a potential and novel therapy for Non‐Alcoholic Fatty Liver Disease in humans.