Creatine supplementation prevents the accumulation of fat in the livers of rats fed a high-fat diet

J Nutr. 2011 Oct;141(10):1799-804. doi: 10.3945/jn.111.144857. Epub 2011 Aug 31.


The aim of the present study was to examine the effects of creatine supplementation on liver fat accumulation induced by a high-fat diet in rats. Rats were fed 1 of 3 different diets for 3 wk: a control liquid diet (C), a high-fat liquid diet (HF), or a high-fat liquid diet supplemented with creatine (HFC). The C and HF diets contained, respectively, 35 and 71% of energy derived from fat. Creatine supplementation involved the addition of 1% (wt:v) of creatine monohydrate to the liquid diet. The HF diet increased total liver fat concentration, liver TG, and liver TBARS and decreased the hepatic S-adenosylmethionine (SAM) concentration. Creatine supplementation normalized all of these perturbations. Creatine supplementation significantly decreased the renal activity of l-arginine:glycine amidinotransferase and plasma guanidinoacetate and prevented the decrease in hepatic SAM concentration in rats fed the HF diet. However, there was no change in either the phosphatidylcholine:phosphatidylethanolamine (PE) ratio or PE N-methyltransferase activity. The HF diet decreased mRNA for PPARα as well as 2 of its targets, carnitine palmitoyltransferase and long-chain acylCoA dehydrogenase. Creatine supplementation normalized these mRNA levels. In conclusion, creatine supplementation prevented the fatty liver induced by feeding rats a HF diet, probably by normalization of the expression of key genes of β-oxidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Dehydrogenase, Long-Chain / genetics
  • Acyl-CoA Dehydrogenase, Long-Chain / metabolism
  • Amidinotransferases / metabolism
  • Animals
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Creatine / blood
  • Creatine / therapeutic use*
  • Dietary Fats / adverse effects*
  • Dietary Supplements*
  • Fatty Liver / blood
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Fatty Liver / prevention & control*
  • Gene Expression Regulation
  • Glycine / analogs & derivatives
  • Glycine / blood
  • Kidney / enzymology
  • Lipid Metabolism*
  • Lipid Peroxidation
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • S-Adenosylmethionine / metabolism


  • Dietary Fats
  • PPAR alpha
  • RNA, Messenger
  • S-Adenosylmethionine
  • Acyl-CoA Dehydrogenase, Long-Chain
  • Amidinotransferases
  • glycine amidinotransferase
  • Carnitine O-Palmitoyltransferase
  • glycocyamine
  • Creatine
  • Glycine