Influence of conjugated linoleic acid on body composition and target gene expression in peroxisome proliferator-activated receptor alpha-null mice.

The mechanisms underlying the beneficial effects of conjugated linoleic acid (CLA) are unknown, but one hypothesis is that they are mediated by the nuclear receptor, peroxisome proliferator-activated receptor (PPARalpha). In this work, the effect of dietary CLA on body weight gain, body composition, serum lipids and tissue specific PPAR target gene expression was examined in PPARalpha-null mice. Male wild-type or PPARalpha-null mice were fed either a control diet or one containing 0.5% CLA for a period of 4 weeks. Weight gain in wild-type and PPARalpha-null mice fed CLA was similar, and significantly less than controls. Whole body fat content was lower in wild-type and PPARalpha-null mice while whole body protein content was increased in both genotypes fed CLA compared to controls. Serum triglycerides were lowered in both genotypes as a result of dietary CLA. While CLA feeding resulted in specific activation of PPARalpha in liver, alterations in liver, adipose and muscle mRNAs were also found that were independent of PPARalpha genotype including those encoding uncoupling proteins (UCPs), mitochondrial fatty acid oxidizing enzymes, and fatty acid transporter. These results demonstrate that despite specific activation of PPARalpha-dependent gene expression, the influence of CLA on body composition appears to be independent of PPARalpha. Further, CLA causes increased levels of mRNAs encoding lipid metabolizing and mitochondrial uncoupling proteins that likely contribute to the mechanisms underlying reduced fat/increased lean body mass resulting from consumption of dietary CLA.