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Molecular and Cellular Biology, February 2000, p. 1008-1020, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

CREB Activation Induces Adipogenesis in 3T3-L1 Cells

Jane E. B. Reusch,1,2 Lilliester A. Colton,3,4 and Dwight J. Klemm3,4,*

Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206,3 and Research Service, Veterans Affairs Medical Center,1 and Departments of Biochemistry and Molecular Genetics4 and of Medicine,2 University of Colorado Health Sciences Center, Denver, Colorado 80220

Received 16 July 1999/Returned for modification 15 September 1999/Accepted 11 October 1999

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.

* Corresponding author. Mailing address: National Jewish Medical and Research Center, 1400 Jackson St., K613c, Denver, CO 80206. Phone: (303) 398-1160. Fax: (303) 398-1806. E-mail: klemmd{at}njc.org.

Molecular and Cellular Biology, February 2000, p. 1008-1020, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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