Isomer-specific regulation of metabolism and PPARgamma signaling by CLA in human preadipocytes

J Lipid Res. 2003 Jul;44(7):1287-300. doi: 10.1194/jlr.M300001-JLR200. Epub 2003 May 1.


Trans-10,cis-12 conjugated linoleic acid (CLA) has previously been shown to be the CLA isomer responsible for CLA-induced reductions in body fat in animal models, and we have shown that this isomer, but not the cis-9,trans-11 CLA isomer, specifically decreased triglyceride (TG) accumulation in primary human adipocytes in vitro. Here we investigated the mechanism behind the isomer-specific, CLA-mediated reduction in TG accumulation in differentiating human preadipocytes. Trans-10,cis-12 CLA decreased insulin-stimulated glucose uptake and oxidation, and reduced insulin-dependent glucose transporter 4 gene expression. Furthermore, trans-10,cis-12 CLA reduced oleic acid uptake and oxidation when compared with all other treatments. In parallel to CLA's effects on metabolism, trans-10,cis-12 CLA decreased, whereas cis-9,trans-11 CLA increased, the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and several of its downstream target genes when compared with vehicle controls. Transient transfections demonstrated that both CLA isomers antagonized ligand-dependent activation of PPARgamma. Collectively, trans-10,cis-12, but not cis-9, trans-11, CLA decreased glucose and lipid uptake and oxidation and preadipocyte differentiation by altering preadipocyte gene transcription in a manner that appeared to be due, in part, to decreased PPARgamma expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Adipose Tissue / metabolism
  • Animals
  • Antimetabolites / pharmacology
  • Carbon Dioxide / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Chromatography, Gas
  • Deoxyglucose / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Fatty Acids / metabolism
  • Gene Expression Regulation
  • Glucose / metabolism
  • Humans
  • Immunoblotting
  • Linoleic Acids, Conjugated / metabolism*
  • Lipid Metabolism
  • Mice
  • Oleic Acid / pharmacokinetics
  • Oligonucleotides / chemistry
  • Oxygen / metabolism
  • Phospholipids / metabolism
  • Protein Isoforms
  • RNA / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Time Factors
  • Transcription Factors / metabolism*
  • Transfection
  • Triglycerides / metabolism
  • Water / chemistry


  • Antimetabolites
  • Fatty Acids
  • Linoleic Acids, Conjugated
  • Oligonucleotides
  • Phospholipids
  • Protein Isoforms
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Triglycerides
  • Water
  • Carbon Dioxide
  • Oleic Acid
  • RNA
  • Deoxyglucose
  • Glucose
  • Oxygen