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Molecular and Cellular Biology, February 2000, p. 1008-1020, Vol. 20, No. 3
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.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
CREB Activation Induces Adipogenesis in
3T3-L1 Cells
*
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.
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