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Science 289 (5481): 950-953

Copyright © 2000 by the American Association for the Advancement of Science

Inhibition of Adipogenesis by Wnt Signaling

Sarah E. Ross,1 Nahid Hemati,1 Kenneth A. Longo,1 Christina N. Bennett,1 Peter C. Lucas,2 Robin L. Erickson,1 Ormond A. MacDougald1*

Wnts are secreted signaling proteins that regulate developmental processes. Here we show that Wnt signaling, likely mediated by Wnt-10b, is a molecular switch that governs adipogenesis. Wnt signaling maintains preadipocytes in an undifferentiated state through inhibition of the adipogenic transcription factors CCAAT/enhancer binding protein alpha  (C/EBPalpha ) and peroxisome proliferator- activated receptor gamma  (PPARgamma ). When Wnt signaling in preadipocytes is prevented by overexpression of Axin or dominant-negative TCF4, these cells differentiate into adipocytes. Disruption of Wnt signaling also causes transdifferentiation of myoblasts into adipocytes in vitro, highlighting the importance of this pathway not only in adipocyte differentiation but also in mesodermal cell fate determination.

1 Department of Physiology,
2 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0622, USA.
*   To whom correspondence should be addressed. E-mail: macdouga{at}

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V. Marion, C. Stoetzel, D. Schlicht, N. Messaddeq, M. Koch, E. Flori, J. M. Danse, J.-L. Mandel, and H. Dollfus (2009)
PNAS 106, 1820-1825
   Abstract »    Full Text »    PDF »
Dynamic complexes of A-type lamins and emerin influence adipogenic capacity of the cell via nucleocytoplasmic distribution of {beta}-catenin.
K. Tilgner, K. Wojciechowicz, C. Jahoda, C. Hutchison, and E. Markiewicz (2009)
J. Cell Sci. 122, 401-413
   Abstract »    Full Text »    PDF »
The role of Dickkopf-1 in bone development, homeostasis, and disease.
J. J. Pinzone, B. M. Hall, N. K. Thudi, M. Vonau, Y.-W. Qiang, T. J. Rosol, and J. D. Shaughnessy Jr (2009)
Blood 113, 517-525
   Abstract »    Full Text »    PDF »
SPARC Inhibits Adipogenesis by Its Enhancement of {beta}-Catenin Signaling.
J. Nie and E. H. Sage (2009)
J. Biol. Chem. 284, 1279-1290
   Abstract »    Full Text »    PDF »
LRP1 Controls Intracellular Cholesterol Storage and Fatty Acid Synthesis through Modulation of Wnt Signaling.
J. Terrand, V. Bruban, L. Zhou, W. Gong, Z. El Asmar, P. May, K. Zurhove, P. Haffner, C. Philippe, E. Woldt, et al. (2009)
J. Biol. Chem. 284, 381-388
   Abstract »    Full Text »    PDF »
Gene expression patterns during intramuscular fat development in cattle.
Y. H. Wang, N. I. Bower, A. Reverter, S. H. Tan, N. De Jager, R. Wang, S. M. McWilliam, L. M. Cafe, P. L. Greenwood, and S. A. Lehnert (2009)
J Anim Sci 87, 119-130
   Abstract »    Full Text »    PDF »
Regulation of Cyclin D1 and Wnt10b Gene Expression by cAMP-responsive Element-binding Protein during Early Adipogenesis Involves Differential Promoter Methylation.
K. E. Fox, L. A. Colton, P. F. Erickson, J. E. Friedman, H. C. Cha, P. Keller, O. A. MacDougald, and D. J. Klemm (2008)
J. Biol. Chem. 283, 35096-35105
   Abstract »    Full Text »    PDF »
Identification of genes downregulated during differentiation of porcine mesenteric adipocytes.
S. Suzuki, S. Sembon, M. Iwamoto, D. Fuchimoto, and A. Onishi (2008)
J Anim Sci 86, 3367-3376
   Abstract »    Full Text »    PDF »
Mesoderm-specific transcript is associated with fat mass expansion in response to a positive energy balance.
L. Nikonova, R. A. Koza, T. Mendoza, P.-M. Chao, J. P. Curley, and L. P. Kozak (2008)
FASEB J 22, 3925-3937
   Abstract »    Full Text »    PDF »
Msx2 Exerts Bone Anabolism via Canonical Wnt Signaling.
S.-L. Cheng, J.-S. Shao, J. Cai, O. L. Sierra, and D. A. Towler (2008)
J. Biol. Chem. 283, 20505-20522
   Abstract »    Full Text »    PDF »
Phosphorylation of CCAAT/Enhancer-binding Protein {alpha} Regulates GLUT4 Expression and Glucose Transport in Adipocytes.
H. C. Cha, N. R. Oak, S. Kang, T.-A. Tran, S. Kobayashi, S.-H. Chiang, D. G. Tenen, and O. A. MacDougald (2008)
J. Biol. Chem. 283, 18002-18011
   Abstract »    Full Text »    PDF »
Genome-wide association scans identified CTNNBL1 as a novel gene for obesity.
Y.-J. Liu, X.-G. Liu, L. Wang, C. Dina, H. Yan, J.-F. Liu, S. Levy, C. J. Papasian, B. M. Drees, J. J. Hamilton, et al. (2008)
Hum. Mol. Genet. 17, 1803-1813
   Abstract »    Full Text »    PDF »

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