title: CREB activation induces adipogenesis in 3T3-L1 cells.
abstract: Obesity is the result of numerous, interacting behavioral, physiological, and 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 adipocytes is controlled by several "adipocyte-specific" transcription factors that regulate preadipocyte proliferation and adipogenesis. Generally these adipocyte-specific factors are expressed only following the induction of adipogenesis. The transcription factor(s) that are involved in initiating adipocyte differentiation have not been identified. Here we demonstrate that the transcription factor, CREB, is constitutively expressed in preadipocytes and throughout the differentiation process and that CREB is stimulated by conventional differentiation-inducing agents such as insulin, dexamethasone, and dibutyryl cAMP. Stably transfected 3T3-L1 preadipocytes were generated in which we could induce the expression of either a constitutively active CREB (VP16-CREB) or a dominant-negative CREB (KCREB). Inducible expression of VP16-CREB alone was sufficient to initiate adipogenesis as determined by triacylglycerol storage, cell morphology, and the expression of two adipocyte marker genes, peroxisome proliferator activated receptor gamma 2, and fatty acid binding protein. Alternatively, KCREB alone blocked adipogenesis in cells treated with conventional differentiation-inducing agents. These data indicate that activation of CREB was necessary and sufficient to induce adipogenesis. Finally, CREB was shown to bind to putative CRE sequences in the promoters of several adipocyte-specific genes. These data firmly establish CREB as a primary regulator of adipogenesis and suggest that CREB may play similar roles in other cells and tissues.
authors.affiliation: Research Service, Veterans Affairs Medical Center, Denver, Colorado 80220, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Reusch
authors.forename: L A
authors.initials: LA
authors.lastname: Colton
authors.forename: D J
authors.initials: DJ
authors.lastname: Klemm
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D016384:Consensus Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D017930:Genes, Reporter; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D018996:Myelin P2 Protein / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D016366:Open Reading Frames; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D000943:Antigens, Differentiation; D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D003994:Bucladesine