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.