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 aci d (CLA) are unknown, but one hypothesis is that they are mediated by the nu clear receptor, peroxisome proliferator-activated receptor (PPAR alpha). 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 PPAR alpha -null mice. Male wild-type or PPAR alpha -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 PPAR alpha -null mice fed CLA was similar, and significantly less than controls. Whole body fat content was lower in wild -type and PPAR alpha -null mice while whole body protein content was increa sed in both genotypes fed CLA compared to controls. Serum triglycerides wer e lowered in both genotypes as a result of dietary CLA. While CLA feeding r esulted in specific activation of PPAR alpha in liver, alterations in Ever, adipose and muscle mRNAs were also found that were independent of PPAR alp ha genotype including those encoding uncoupling proteins (UCPs), mitochondr ial fatty acid oxidizing enzymes, and fatty acid transporter. These results demonstrate that despite specific activation of PPAR alpha -dependent gene expression, the influence of CLA on body composition appears to be indepen dent of PPAR alpha. Further, CLA causes increased levels of mRNAs encoding lipid metabolizing and mitochondrial uncoupling proteins that likely contri bute to the mechanisms underlying reduced fat/increased lean body mass resu lting from consumption of dietary CLA. (C) 2001 Elsevier Science B.V. All r ights reserved.