Conjugated linoleic acid activates peroxisome proliferator-activated receptor α and β 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 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 PPARα in transfected cells to a similar extent as Wy-14,643, whereas the furan-CLA metabolite was comparable to bezafibrate on activating PPARβ. These data suggest that while CLA was able to activate PPARs it is not a peroxisome proliferator in SD rats