Expression of peroxisome proliferator-activated receptor PPAR delta promotes induction of PPAR gamma and adipocyte differentiation in 3T3C2 fibroblasts

Nutritional long chain fatty acids control adipose tissue mass by regulatin g the number and the size of adipocytes. The molecular mechanisms implicate d in this action of fatty acids remain poorly understood. It has been well established that peroxisome proliferator-activated receptor (PPAR) gamma, a ctivated by specific prostanoids, plays a central role in the control of ad ipocyte gene expression and terminal differentiation. Thus far, the role of PPAR delta in the control of adipose tissue mass has remained unclear. Her ein, we report the effects of ectopically expressed PPAR delta on the contr ol of adipose-related gene expression and adipogenesis of 3T3C2 fibroblasts . Treatment of PPAR delta-expressing fibroblasts with fatty acids alone did not stimulate adipogenesis, whereas exposure of cells to a combination of fatty acids and PPAR gamma activators promoted lipid accumulation and expre ssion of a typical adipocyte program. At the molecular level, activation of PPAR delta by fatty acids induced transcription of the genes encoding fatt y acid transporter, adipocyte lipid-binding protein, and PPAR gamma. Subseq uent activation of PPAR gamma by specific agonists appeared to be required to promote terminal differentiation. These data demonstrate that PPAR gamma gene expression is under the control of PPAR delta activated by fatty acid s and could explain, at least partially, the adipogenic action of nutrition al fatty acids.