Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse

J Lipid Res. 2002 Sep;43(9):1400-9. doi: 10.1194/jlr.m20008-jlr200.


Conjugated linoleic acids (CLA) are a class of positional, geometric, conjugated dienoic isomers of linoleic acid (LA). Dietary CLA supplementation results in a dramatic decrease in body fat mass in mice, but also causes considerable liver steatosis. However, little is known of the molecular mechanisms leading to hepatomegaly. Although c9,t11- and t10,c12-CLA isomers are found in similar proportions in commercial preparations, the respective roles of these two molecules in liver enlargement has not been studied. We show here that mice fed a diet enriched in t10,c12-CLA (0.4% w/w) for 4 weeks developed lipoatrophy, hyperinsulinemia, and fatty liver, whereas diets enriched in c9,t11-CLA and LA had no significant effect. In the liver, dietary t10,c12-CLA triggered the ectopic production of peroxisome proliferator-activated receptor gamma (PPARgamma), adipocyte lipid-binding protein and fatty acid transporter mRNAs and induced expression of the sterol responsive element-binding protein-1a and fatty acid synthase genes. In vitro transactivation assays demonstrated that t10,c12- and c9,t11-CLA were equally efficient at activating PPARalpha, beta/delta, and gamma and inhibiting liver-X-receptor. Thus, the specific effect of t10,c12-CLA is unlikely to result from direct interaction with these nuclear receptors. Instead, t10,c12-CLA-induced hyperinsulinemia may trigger liver steatosis, by inducing both fatty acid uptake and lipogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Body Composition / drug effects
  • Body Weight / drug effects
  • DNA-Binding Proteins
  • Dietary Fats / pharmacology*
  • Energy Metabolism / drug effects
  • Fatty Liver / blood
  • Fatty Liver / chemically induced*
  • Fatty Liver / genetics
  • Female
  • Gene Expression Regulation / drug effects
  • Hyperinsulinism / blood
  • Hyperinsulinism / chemically induced*
  • Hyperinsulinism / genetics
  • Insulin / blood
  • Isomerism
  • Linoleic Acid / administration & dosage*
  • Linoleic Acid / chemistry
  • Linoleic Acid / pharmacology*
  • Liver / drug effects
  • Liver / metabolism
  • Liver X Receptors
  • Mice
  • Orphan Nuclear Receptors
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • Dietary Fats
  • Insulin
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Linoleic Acid