Conjugated linoleic acid activates peroxisome proliferator-activated receptor alpha and beta subtypes but does not induce hepatic peroxisome proliferation in Sprague-Dawley rats.
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.
Moya-Camarena
S Y
SY
Department of Foods and Nutrition, Purdue University, West Lafayette, IN 47907, USA.
Van den Heuvel
J P
JP
Belury
M A
MA
D042962:Acyl-CoA Oxidase; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D004032:Diet; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008041:Linoleic Acids / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D018996:Myelin P2 Protein / Q000235:genetics; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010088:Oxidoreductases / Q000235:genetics; D020025:Peroxisome Proliferators / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection