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

Abstract

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 PPARγ or PPARδ promotes adipogenesis in fibroblastic cells exposed to thiazolidinediones or long-chain fatty acids. To investigate the role of PPARδ 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 PPARδ mutant in Ob1771 and 3T3-F442A cells. Overexpression of PPARδ enhanced fatty acid induction of the adipose-related genes for fatty acid translocase, adipocyte lipid binding protein, and PPARγ and fatty acid effects on terminal differentiation. A transactivation-deficient form of PPARδ mutated in the AF2 domain severely reduced these effects. Findings are similar in Ob1771 or 3T3-F442A preadipose cells. These data demonstrate that PPARδ plays a central role in fatty acid-controlled differentiation of preadipose cells. Furthermore, they suggest that modulation of PPARδ expression or activity could affect adaptive responses of white adipose tissue to nutritional changes.