Expression of peroxisome proliferator-activated receptor PPARdelta promotes induction of PPARgamma and adipocyte differentiation in 3T3C2 fibroblasts.
Nutritional long chain fatty acids control adipose tissue mass by regulating the number and the size of adipocytes. The molecular mechanisms implicated in this action of fatty acids remain poorly understood. It has been well established that peroxisome proliferator-activated receptor (PPAR) gamma, activated by specific prostanoids, plays a central role in the control of adipocyte gene expression and terminal differentiation. Thus far, the role of PPARdelta in the control of adipose tissue mass has remained unclear. Herein, we report the effects of ectopically expressed PPARdelta on the control of adipose-related gene expression and adipogenesis of 3T3C2 fibroblasts. Treatment of PPARdelta-expressing fibroblasts with fatty acids alone did not stimulate adipogenesis, whereas exposure of cells to a combination of fatty acids and PPARgamma activators promoted lipid accumulation and expression of a typical adipocyte program. At the molecular level, activation of PPARdelta by fatty acids induced transcription of the genes encoding fatty acid transporter, adipocyte lipid-binding protein, and PPARgamma. Subsequent activation of PPARgamma by specific agonists appeared to be required to promote terminal differentiation. These data demonstrate that PPARgamma gene expression is under the control of PPARdelta activated by fatty acids and could explain, at least partially, the adipogenic action of nutritional fatty acids.
Centre de Biochimie, INSERM U470, Parc Valrose, UFR Sciences, Université de Nice-Sophia Antipolis, 06108 Nice Cedex 2, France.
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Bastie
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Holst
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Gaillard
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Jehl-Pietri
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Grimaldi
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002454:Cell Differentiation; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D018996:Myelin P2 Protein / Q000235:genetics; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010168:Palmitates / Q000494:pharmacology; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D002352:Carrier Proteins; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010168:Palmitates; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D014157:Transcription Factors; C022776:2-bromopalmitate