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Nutritional long-chain fatty acids control adipose tissue mass by regulating the number and the size of adipocytes.It is now established that peroxisome-proliferator-activated receptors (PPARs) play crucial functions in the control of gene expression and the level of cell differentiation.PPARγ, which is activated by specific prostanoids, is a key factor in activating terminal differentiation and adipogenesis.We have recently demonstrated that PPARδ, once activated by fatty acids, drives the expression of a limited set of genes, including that encoding PPARγ, thereby inducing adipose differentiation.Thus far, the mechanism of action of fatty acids in the control of preadipocyte proliferation has remained unknown.We show here that PPARδ is directly implicated in fatty acid-induced cell proliferation.Ectopic expression of PPARδ renders 3T3C2 cells capable of responding to Abbreviations used : AF-2, activation function-2 ; ALBP, adipocyte lipid binding protein ; BrdU, 5-bromo-2h-deoxyuridine ; FAT, fatty acid translocase ; PPAR, peroxisome-proliferator-activated receptor ; PPRE, PPAR-responsive element ; RXR, retinoid X receptor.1 To whom correspondence should be addressed (e-mail grimaldi!taloa.unice.fr
Jehl-Piétri et al. (Tue,) studied this question.