Alterations of peroxisome proliferator-activated receptor δ activity affect fatty acid-controlled adipose differentiation

Fatty acids have been postulated to regulate adaptation of adipose mass to nutritional changes by controlling expression of genes implicated in lipid metabolism via activation of nuclear receptors. Ectopic expression of the nuclear receptors PPAR gamma or PPAR delta promotes adipogenesis in fibroblastic cells exposed to thiazolidinediones or long-chain fatty acids. To investigate the role of PPAR delta in fatty acid regulation of gene expression and adipogenesis in a preadipose cellular context, we studied the effects of overexpressing the native receptor or the dominant-negative PPAR delta mutant in Ob1771 and 3T3-F442A cells. Overexpression of PPAR delta enhanced fatty acid induction of the adipose-related genes for fatty acid translocase, adipocyte lipid binding protein, and PPAR gamma and fatty acid effects on terminal differentiation. A transactivation deficient form of PPAR delta mutated in the AF2 domain severely reduced these effects. Findings are similar in Ob1771 or 3T3-F442A preadipose cells. These data demonstrate that PPAR delta plays a central role in fatty acid-controlled differentiation of preadipose cells. Furthermore, they suggest that modulation of PPAR delta expression or activity could affect adaptive responses of white adipose tissue to nutritional changes.