This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Reusch, J. E. B.
Right arrow Articles by Klemm, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Reusch, J. E. B.
Right arrow Articles by Klemm, D. J.

 Previous Article  |  Next Article 

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.


This article has been cited by other articles:

  • Chen, W., Yechoor, V. K., Chang, B. H.-J., Li, M. V., March, K. L., Chan, L. (2009). The Human Lipodystrophy Gene Product Berardinelli-Seip Congenital Lipodystrophy 2/Seipin Plays a Key Role in Adipocyte Differentiation. Endocrinology 150: 4552-4561 [Abstract] [Full Text]  
  • Zhang, L., Paddon, C., Lewis, M. D, Grennan-Jones, F., Ludgate, M. (2009). Gs{alpha} signalling suppresses PPAR{gamma}2 generation and inhibits 3T3L1 adipogenesis. J Endocrinol 202: 207-215 [Abstract] [Full Text]  
  • Muraoka, M., Fukushima, A., Viengchareun, S., Lombes, M., Kishi, F., Miyauchi, A., Kanematsu, M., Doi, J., Kajimura, J., Nakai, R., Uebi, T., Okamoto, M., Takemori, H. (2009). Involvement of SIK2/TORC2 signaling cascade in the regulation of insulin-induced PGC-1{alpha} and UCP-1 gene expression in brown adipocytes. Am. J. Physiol. Endocrinol. Metab. 296: E1430-E1439 [Abstract] [Full Text]  
  • Fox, K. E., Colton, L. A., Erickson, P. F., Friedman, J. E., Cha, H. C., Keller, P., MacDougald, O. A., Klemm, D. J. (2008). Regulation of Cyclin D1 and Wnt10b Gene Expression by cAMP-responsive Element-binding Protein during Early Adipogenesis Involves Differential Promoter Methylation. J. Biol. Chem. 283: 35096-35105 [Abstract] [Full Text]  
  • Deng, X., Liu, H., Huang, J., Cheng, L., Keller, E. T., Parsons, S. J., Hu, C.-D. (2008). Ionizing Radiation Induces Prostate Cancer Neuroendocrine Differentiation through Interplay of CREB and ATF2: Implications for Disease Progression. Cancer Res. 68: 9663-9670 [Abstract] [Full Text]  
  • Szabo, E., Qiu, Y., Baksh, S., Michalak, M., Opas, M. (2008). Calreticulin inhibits commitment to adipocyte differentiation. JCB 182: 103-116 [Abstract] [Full Text]  
  • Petersen, R. K., Madsen, L., Pedersen, L. M., Hallenborg, P., Hagland, H., Viste, K., Doskeland, S. O., Kristiansen, K. (2008). Cyclic AMP (cAMP)-Mediated Stimulation of Adipocyte Differentiation Requires the Synergistic Action of Epac- and cAMP-Dependent Protein Kinase-Dependent Processes. Mol. Cell. Biol. 28: 3804-3816 [Abstract] [Full Text]  
  • Aggarwal, S., Kim, S.-W., Ryu, S.-H., Chung, W.-C., Koo, J. S. (2008). Growth Suppression of Lung Cancer Cells by Targeting Cyclic AMP Response Element-Binding Protein. Cancer Res. 68: 981-988 [Abstract] [Full Text]  
  • Cheng, J. H., She, H., Han, Y.-P., Wang, J., Xiong, S., Asahina, K., Tsukamoto, H. (2008). Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 294: G39-G49 [Abstract] [Full Text]  
  • Kim, S.-W., Hong, J. S., Ryu, S.-H., Chung, W.-C., Yoon, J.-H., Koo, J. S. (2007). Regulation of Mucin Gene Expression by CREB via a Nonclassical Retinoic Acid Signaling Pathway. Mol. Cell. Biol. 27: 6933-6947 [Abstract] [Full Text]  
  • Kang, S., Bennett, C. N., Gerin, I., Rapp, L. A., Hankenson, K. D., MacDougald, O. A. (2007). Wnt Signaling Stimulates Osteoblastogenesis of Mesenchymal Precursors by Suppressing CCAAT/Enhancer-binding Protein {alpha} and Peroxisome Proliferator-activated Receptor {gamma}. J. Biol. Chem. 282: 14515-14524 [Abstract] [Full Text]  
  • Singh, N. K., Chae, H. S., Hwang, I. H., Yoo, Y. M., Ahn, C. N., Lee, S. H., Lee, H. J., Park, H. J., Chung, H. Y. (2007). Transdifferentiation of porcine satellite cells to adipoblasts with ciglitizone. J ANIM SCI 85: 1126-1135 [Abstract] [Full Text]  
  • Fox, K. E., Fankell, D. M., Erickson, P. F., Majka, S. M., Crossno, J. T. Jr., Klemm, D. J. (2006). Depletion of cAMP-response Element-binding Protein/ATF1 Inhibits Adipogenic Conversion of 3T3-L1 Cells Ectopically Expressing CCAAT/Enhancer-binding Protein (C/EBP) {alpha}, C/EBP beta, or PPAR{gamma}2. J. Biol. Chem. 281: 40341-40353 [Abstract] [Full Text]  
  • Zhang, L., Baker, G., Janus, D., Paddon, C. A., Fuhrer, D., Ludgate, M. (2006). Biological Effects of Thyrotropin Receptor Activation on Human Orbital Preadipocytes. IOVS 47: 5197-5203 [Abstract] [Full Text]  
  • Liu, H., Tang, J. R., Choi, Y. H., Napolitano, M., Hockman, S., Taira, M., Degerman, E., Manganiello, V. C. (2006). Importance of cAMP-response Element-binding Protein in Regulation of Expression of the Murine Cyclic Nucleotide Phosphodiesterase 3B (Pde3b) Gene in Differentiating 3T3-L1 Preadipocytes. J. Biol. Chem. 281: 21096-21113 [Abstract] [Full Text]  
  • Vankoningsloo, S., De Pauw, A., Houbion, A., Tejerina, S., Demazy, C., de Longueville, F., Bertholet, V., Renard, P., Remacle, J., Holvoet, P., Raes, M., Arnould, T. (2006). CREB activation induced by mitochondrial dysfunction triggers triglyceride accumulation in 3T3-L1 preadipocytes. J. Cell Sci. 119: 1266-1282 [Abstract] [Full Text]  
  • Aggarwal, S., Kim, S.-W., Cheon, K., Tabassam, F. H., Yoon, J.-H., Koo, J. S. (2006). Nonclassical Action of Retinoic Acid on the Activation of the cAMP Response Element-binding Protein in Normal Human Bronchial Epithelial Cells. Mol. Biol. Cell 17: 566-575 [Abstract] [Full Text]  
  • Yang, R.-Y., Hsu, D. K., Yu, L., Chen, H.-Y., Liu, F.-T. (2004). Galectin-12 Is Required for Adipogenic Signaling and Adipocyte Differentiation. J. Biol. Chem. 279: 29761-29766 [Abstract] [Full Text]  
  • Serazin, V., Dieudonne, M.-N., Morot, M., de Mazancourt, P., Giudicelli, Y. (2004). cAMP-positive regulation of angiotensinogen gene expression and protein secretion in rat adipose tissue. Am. J. Physiol. Endocrinol. Metab. 286: E434-E438 [Abstract] [Full Text]  
  • Zhang, J.-W., Klemm, D. J., Vinson, C., Lane, M. D. (2004). Role of CREB in Transcriptional Regulation of CCAAT/Enhancer-binding Protein {beta} Gene during Adipogenesis. J. Biol. Chem. 279: 4471-4478 [Abstract] [Full Text]  
  • Shang, C. A., Waters, M. J. (2003). Constitutively Active Signal Transducer and Activator of Transcription 5 Can Replace the Requirement for Growth Hormone in Adipogenesis of 3T3-F442A Preadipocytes. Mol. Endocrinol. 17: 2494-2508 [Abstract] [Full Text]  
  • Cho, K.-J., Moon, H.-E., Moini, H., Packer, L., Yoon, D.-Y., Chung, A.-S. (2003). {alpha}-Lipoic Acid Inhibits Adipocyte Differentiation by Regulating Pro-adipogenic Transcription Factors via Mitogen-activated Protein Kinase Pathways. J. Biol. Chem. 278: 34823-34833 [Abstract] [Full Text]  
  • Fajas, L., Miard, S., Briggs, M. R., Auwerx, J. (2003). Selective cyclo-oxygenase-2 inhibitors impair adipocyte differentiation through inhibition of the clonal expansion phase. J. Lipid Res. 44: 1652-1659 [Abstract] [Full Text]  
  • Rosenberg, D., Groussin, L., Jullian, E., Perlemoine, K., Medjane, S., Louvel, A., Bertagna, X., Bertherat, J. (2003). Transcription Factor 3',5'-Cyclic Adenosine 5'-Monophosphate-Responsive Element-Binding Protein (CREB) Is Decreased during Human Adrenal Cortex Tumorigenesis and Fetal Development. J. Clin. Endocrinol. Metab. 88: 3958-3965 [Abstract] [Full Text]  
  • Horike, N., Takemori, H., Katoh, Y., Doi, J., Min, L., Asano, T., Sun, X. J., Yamamoto, H., Kasayama, S., Muraoka, M., Nonaka, Y., Okamoto, M. (2003). Adipose-specific Expression, Phosphorylation of Ser794 in Insulin Receptor Substrate-1, and Activation in Diabetic Animals of Salt-inducible Kinase-2. J. Biol. Chem. 278: 18440-18447 [Abstract] [Full Text]  
  • Friday, R. P., Pietropaolo, S. L., Profozich, J., Trucco, M., Pietropaolo, M. (2003). Alternative Core Promoters Regulate Tissue-specific Transcription from the Autoimmune Diabetes-related ICA1 (ICA69) Gene Locus. J. Biol. Chem. 278: 853-863 [Abstract] [Full Text]  
  • Neal, J. W., Clipstone, N. A. (2002). Calcineurin Mediates the Calcium-dependent Inhibition of Adipocyte Differentiation in 3T3-L1 Cells. J. Biol. Chem. 277: 49776-49781 [Abstract] [Full Text]  
  • Fu, Q., Jilka, R. L., Manolagas, S. C., O'Brien, C. A. (2002). Parathyroid Hormone Stimulates Receptor Activator of NFkappa B Ligand and Inhibits Osteoprotegerin Expression via Protein Kinase A Activation of cAMP-response Element-binding Protein. J. Biol. Chem. 277: 48868-48875 [Abstract] [Full Text]  
  • Bennett, C. N., Ross, S. E., Longo, K. A., Bajnok, L., Hemati, N., Johnson, K. W., Harrison, S. D., MacDougald, O. A. (2002). Regulation of Wnt Signaling during Adipogenesis. J. Biol. Chem. 277: 30998-31004 [Abstract] [Full Text]  
  • Nanbu-Wakao, R., Morikawa, Y., Matsumura, I., Masuho, Y., Muramatsu, M.-a., Senba, E., Wakao, H. (2002). Stimulation of 3T3-L1 Adipogenesis by Signal Transducer and Activator of Transcription 5. Mol. Endocrinol. 16: 1565-1576 [Abstract] [Full Text]  
  • Gregoire, F. M. (2001). Adipocyte Differentiation: From Fibroblast to Endocrine Cell. Exp. Biol. Med. 226: 997-1002 [Abstract] [Full Text]  
  • Klemm, D. J., Watson, P. A., Frid, M. G., Dempsey, E. C., Schaack, J., Colton, L. A., Nesterova, A., Stenmark, K. R., Reusch, J. E.-B. (2001). cAMP Response Element-binding Protein Content Is a Molecular Determinant of Smooth Muscle Cell Proliferation and Migration. J. Biol. Chem. 276: 46132-46141 [Abstract] [Full Text]  
  • Watson, P. A., Nesterova, A., Burant, C. F., Klemm, D. J., Reusch, J. E.-B. (2001). Diabetes-related Changes in cAMP Response Element-binding Protein Content Enhance Smooth Muscle Cell Proliferation and Migration. J. Biol. Chem. 276: 46142-46150 [Abstract] [Full Text]  
  • Peri, A., Luciani, P., Conforti, B., Baglioni-Peri, S., Cioppi, F., Crescioli, C., Ferruzzi, P., Gelmini, S., Arnaldi, G., Nesi, G., Serio, M., Mantero, F., Mannelli, M. (2001). Variable Expression of the Transcription Factors cAMP Response Element-Binding Protein and Inducible cAMP Early Repressor in the Normal Adrenal Cortex and in Adrenocortical Adenomas and Carcinomas. J. Clin. Endocrinol. Metab. 86: 5443-5449 [Abstract] [Full Text]  
  • Belmonte, N., Phillips, B. W., Massiera, F., Villageois, P., Wdziekonski, B., Saint-Marc, P., Nichols, J., Aubert, J., Saeki, K., Yuo, A., Narumiya, S., Ailhaud, G., Dani, C. (2001). Activation of Extracellular Signal-Regulated Kinases and CREB/ATF-1 Mediate the Expression of CCAAT/Enhancer Binding Proteins {beta} and -{delta} in Preadipocytes. Mol. Endocrinol. 15: 2037-2049 [Abstract] [Full Text]  
  • Rosen, E. D., Walkey, C. J., Puigserver, P., Spiegelman, B. M. (2000). Transcriptional regulation of adipogenesis. Genes Dev. 14: 1293-1307 [Full Text]  
  • Nishizuka, M., Honda, K., Tsuchiya, T., Nishihara, T., Imagawa, M. (2001). RGS2 Promotes Adipocyte Differentiation in the Presence of Ligand for Peroxisome Proliferator-activated Receptor gamma. J. Biol. Chem. 276: 29625-29627 [Abstract] [Full Text]  
  • Wang, L., Shao, J., Muhlenkamp, P., Liu, S., Klepcyk, P., Ren, J., Friedman, J. E. (2000). Increased Insulin Receptor Substrate-1 and Enhanced Skeletal Muscle Insulin Sensitivity in Mice Lacking CCAAT/Enhancer-binding Protein beta. J. Biol. Chem. 275: 14173-14181 [Abstract] [Full Text]  
  • Niehof, M., Streetz, K., Rakemann, T., Bischoff, S. C., Manns, M. P., Horn, F., Trautwein, C. (2001). Interleukin-6-induced Tethering of STAT3 to the LAP/C/EBPbeta Promoter Suggests a New Mechanism of Transcriptional Regulation by STAT3. J. Biol. Chem. 276: 9016-9027 [Abstract] [Full Text]  
  • Klemm, D. J., Leitner, J. W., Watson, P., Nesterova, A., Reusch, J. E.-B., Goalstone, M. L., Draznin, B. (2001). Insulin-induced Adipocyte Differentiation. ACTIVATION OF CREB RESCUES ADIPOGENESIS FROM THE ARREST CAUSED BY INHIBITION OF PRENYLATION. J. Biol. Chem. 276: 28430-28435 [Abstract] [Full Text]  
  • Reusch, J. E. B., Klemm, D. J. (2002). Inhibition of cAMP-response Element-binding Protein Activity Decreases Protein Kinase B/Akt Expression in 3T3-L1 Adipocytes and Induces Apoptosis. J. Biol. Chem. 277: 1426-1432 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»