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

• Published in: The Journal of biological chemistry 2000-12, Vol.275 (49), p.38768-38773
• Main Authors: Bastie, C, Luquet, S, Holst, D, Jehl-Pietri, C, Grimaldi, P A
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Adipocytes - cytology; Adipocytes - physiology; Amino Acid Substitution; Animals; Carrier Proteins - genetics; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Line; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Fatty Acids - metabolism; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Kinetics; Mice; Mutagenesis, Site-Directed; Neoplasm Proteins; Nerve Tissue Proteins; Palmitates - pharmacology; Receptors, Cytoplasmic and Nuclear - drug effects; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - physiology; Recombinant Proteins - drug effects; Recombinant Proteins - metabolism; Transcription Factors - drug effects; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology; Transcription, Genetic - drug effects; Transcriptional Activation; Transfection
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M006450200

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