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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}umich.edu

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Impact of TCF7L2 rs7903146 on Insulin Secretion and Action in Young and Elderly Danish Twins.
L. Wegner, M. S. Hussain, K. Pilgaard, T. Hansen, O. Pedersen, A. Vaag, and P. Poulsen (2008)
J. Clin. Endocrinol. Metab. 93, 4013-4019
   Abstract »    Full Text »    PDF »
Inhibitor of DNA Binding 2 Is a Small Molecule-Inducible Modulator of Peroxisome Proliferator-Activated Receptor-{gamma} Expression and Adipocyte Differentiation.
K. W. Park, H. Waki, C. J. Villanueva, L. A. Monticelli, C. Hong, S. Kang, O. A. MacDougald, A. W. Goldrath, and P. Tontonoz (2008)
Mol. Endocrinol. 22, 2038-2048
   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 »
Sca-1-Expressing Nonmyogenic Cells Contribute to Fibrosis in Aged Skeletal Muscle.
M. Hidestrand, S. Richards-Malcolm, C. M. Gurley, G. Nolen, B. Grimes, A. Waterstrat, G. V. Zant, and C. A. Peterson (2008)
J Gerontol A Biol Sci Med Sci 63, 566-579
   Abstract »    Full Text »    PDF »
Fat-specific Protein 27 Regulates Storage of Triacylglycerol.
P. Keller, J. T. Petrie, P. De Rose, I. Gerin, W. S. Wright, S.-H. Chiang, A. R. Nielsen, C. P. Fischer, B. K. Pedersen, and O. A. MacDougald (2008)
J. Biol. Chem. 283, 14355-14365
   Abstract »    Full Text »    PDF »
The Effects of Myostatin on Adipogenic Differentiation of Human Bone Marrow-derived Mesenchymal Stem Cells Are Mediated through Cross-communication between Smad3 and Wnt/{beta}-Catenin Signaling Pathways.
W. Guo, J. Flanagan, R. Jasuja, J. Kirkland, L. Jiang, and S. Bhasin (2008)
J. Biol. Chem. 283, 9136-9145
   Abstract »    Full Text »    PDF »
Gene Expression Analyses in Cynomolgus Monkeys Provides Mechanistic Insight into High-Density Lipoprotein-Cholesterol Reduction by Androgens in Primates.
P. Nantermet, S.-i. Harada, Y. Liu, S. Cheng, C. Johnson, Y. Yu, D. Kimme, D. Holder, P. Hodor, R. Phillips, et al. (2008)
Endocrinology 149, 1551-1561
   Abstract »    Full Text »    PDF »
Modulation of Dickkopf-1 Attenuates Glucocorticoid Induction of Osteoblast Apoptosis, Adipocytic Differentiation, and Bone Mass Loss.
F.-S. Wang, J.-Y. Ko, D.-W. Yeh, H.-C. Ke, and H.-L. Wu (2008)
Endocrinology 149, 1793-1801
   Abstract »    Full Text »    PDF »
Glucagon-like Peptide-1 Activation of TCF7L2-dependent Wnt Signaling Enhances Pancreatic Beta Cell Proliferation.
Z. Liu and J. F. Habener (2008)
J. Biol. Chem. 283, 8723-8735
   Abstract »    Full Text »    PDF »
A small-molecule inhibitor of Tcf/{beta}-catenin signaling down-regulates PPAR{gamma} and PPAR{delta} activities.
S. Handeli and J. A. Simon (2008)
Mol. Cancer Ther. 7, 521-529
   Abstract »    Full Text »    PDF »
Wnt/Notch signalling and information processing during development.
P. Hayward, T. Kalmar, and A. Martinez Arias (2008)
Development 135, 411-424
   Abstract »    Full Text »    PDF »
Osteoblasts Directly Control Lineage Commitment of Mesenchymal Progenitor Cells through Wnt Signaling.
H. Zhou, W. Mak, Y. Zheng, C. R. Dunstan, and M. J. Seibel (2008)
J. Biol. Chem. 283, 1936-1945
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FAD24 Acts in Concert with Histone Acetyltransferase HBO1 to Promote Adipogenesis by Controlling DNA Replication.
Y. Johmura, S. Osada, M. Nishizuka, and M. Imagawa (2008)
J. Biol. Chem. 283, 2265-2274
   Abstract »    Full Text »    PDF »
Pitx2 Prevents Osteoblastic Transdifferentiation of Myoblasts by Bone Morphogenetic Proteins.
M. Hayashi, S. Maeda, H. Aburatani, K. Kitamura, H. Miyoshi, K. Miyazono, and T. Imamura (2008)
J. Biol. Chem. 283, 565-571
   Abstract »    Full Text »    PDF »

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