Conjugated linoleic acid activates peroxisome proliferator-activated receptor alpha and beta subtypes but does not induce hepatic peroxisome proliferation in Sprague-Dawley rats

Biochim Biophys Acta. 1999 Jan 4;1436(3):331-42. doi: 10.1016/s0005-2760(98)00121-0.

Abstract

Since conjugated linoleic acid (CLA) has structural and physiological characteristics similar to peroxisome proliferators, we hypothesized that CLA would activate peroxisome proliferator-activated receptor (PPAR). We compared the effects of dietary CLA (0.0, 0.5, 1.0 and 1.5% by weight) with a peroxisome proliferator (0.01% Wy-14,643) in female and male Sprague-Dawley (SD) rats. Dietary CLA had little effect on body weight, liver weight, and hepatic peroxisome proliferation, compared to male rats fed Wy-14,643 diet. Lipid content in livers from rats fed 1.5% CLA and Wy-14,643 diets was increased (P < 0.01) when compared to rats fed control diets regardless of gender. Hepatic acyl-CoA oxidase (ACO) mRNA levels were increased 3-fold in male rats fed 1.5% CLA diet compared to rats fed control diets while Wy-14,643 supported approximately 30-fold ACO mRNA accumulation. A similar response was observed for liver fatty acid-binding protein (L-FABP) mRNA. The effect of dietary treatments on hepatic PPAR-responsive genes in female rats was weaker than in male rats. The (9Z,11E)-CLA isomer activated PPAR alpha in transfected cells to a similar extent as Wy-14,643, whereas the furan-CLA metabolite was comparable to bezafibrate on activating PPAR beta. These data suggest that while CLA was able to activate PPARs it is not a peroxisome proliferator in SD rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Oxidase
  • Animals
  • Bezafibrate / pharmacology
  • Carrier Proteins / genetics
  • Cell Line
  • Diet
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Female
  • Gene Expression / drug effects
  • Genes, Reporter
  • Hypolipidemic Agents / pharmacology
  • Linoleic Acids / chemistry
  • Linoleic Acids / pharmacology*
  • Liver / drug effects*
  • Liver / metabolism*
  • Liver / ultrastructure
  • Male
  • Microbodies / drug effects*
  • Microbodies / metabolism
  • Microbodies / ultrastructure
  • Microscopy, Electron
  • Myelin P2 Protein / genetics
  • Neoplasm Proteins*
  • Nerve Tissue Proteins*
  • Oxidoreductases / genetics
  • Peroxisome Proliferators / pharmacology
  • Pyrimidines / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear / drug effects*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Transcription Factors / drug effects*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • Carrier Proteins
  • Fabp1 protein, mouse
  • Fabp1 protein, rat
  • Fabp7 protein, rat
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Hypolipidemic Agents
  • Linoleic Acids
  • Myelin P2 Protein
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Peroxisome Proliferators
  • Pyrimidines
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • pirinixic acid
  • Oxidoreductases
  • Acyl-CoA Oxidase
  • Bezafibrate