CREB activation induces adipogenesis in 3T3-L1 cells

Obesity is the result of numerous, interacting behavioral, physiological, a nd biochemical factors. One increasingly important factor is the generation of additional fat cells, or adipocytes, in response to excess feeding and/ or large increases in body fat composition. The generation of new adipocyte s is controlled by several "adipocyte-specific'' transcription factors that regulate preadipocyte proliferation and adipogenesis. Generally these adip ocyte-specific factors are expressed only following the induction of adipog enesis. The transcription factor(s) that are involved in initiating adipocy te differentiation have not been identified, Here we demonstrate that the t ranscription factor, CREB, is constitutively expressed in preadipctcytes an d throughout the differentiation process and that CREB is stimulated by con ventional differentiation-inducing agents such as insulin, dexamethasone, a nd dibutyryl cAMP, Stably transfected 3T3-L1 preadipocytes were generated i n which we could induce the expression of either a constitutively active CR EB (VP16-CREB) or a dominant-negative CREB (KCREB), Inducible expression of VP16-CREB alone was sufficient to initiate adipogenesis as determined by t riacylglycerol storage, cell morphology, and the expression of two adipocyt e marker genes, peroxisome proliferator activated receptor gamma 2, and fat ty acid binding protein. Alternatively, KCREB alone blocked adipogenesis in cells treated with conventional differentiation-inducing agents, These dat a indicate that activation of CREB was necessary and sufficient to induce a dipogenesis. Finally, CREB was shown to bind to putative CRE sequences in t he promoters of several adipocyte-specific genes. These data firmly establi sh CREB as a primary regulator of adipogenesis and suggest that CREB may pl ay similar roles in other cells and tissues.