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PMID: 10937998 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of adipogenesis by Wnt signaling.

Science (New York, N.Y.) ·Vol. 289 ·No. 5481 ·2000-08-11 ·Pages 950-3

Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL, MacDougald OA

Abstract

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.

MeSH Terms

3T3 Cells Adipocytes/cytology,metabolism Animals Axin Protein CCAAT-Enhancer-Binding Proteins Cell Differentiation Cell Lineage Cytoskeletal Proteins/metabolism DNA-Binding Proteins/antagonists & inhibitors,genetics,metabolism Gene Transfer Techniques Genetic Vectors Mesoderm/cytology Mice Mice, Nude Muscles/cytology,metabolism Nuclear Proteins/antagonists & inhibitors,genetics,metabolism Proteins/genetics,metabolism Proto-Oncogene Proteins/genetics,metabolism Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors,genetics,metabolism Repressor Proteins Retroviridae/genetics,physiology Signal Transduction TCF Transcription Factors Trans-Activators Transcription Factor 7-Like 2 Protein Transcription Factors/antagonists & inhibitors,genetics,metabolism Wnt Proteins Zebrafish Proteins beta Catenin

Chemicals

Axin Protein CCAAT-Enhancer-Binding Proteins CTNNB1 protein, mouse Cytoskeletal Proteins DNA-Binding Proteins Nuclear Proteins Proteins Proto-Oncogene Proteins Receptors, Cytoplasmic and Nuclear Repressor Proteins TCF Transcription Factors Tcf7l2 protein, mouse Trans-Activators Transcription Factor 7-Like 2 Protein Transcription Factors Wnt Proteins Wnt10b protein, mouse Zebrafish Proteins beta Catenin

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

Ross S E

Department of Physiology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0622, USA.

Hemati N

Longo K A

Bennett C N

Lucas P C

Erickson R L

MacDougald O A

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.289.5481.950

Published

2000-08-11

Pages

950-3

Language

English

Region

United States

NLM ID

0404511

Subset

Grants

NIDDK NIH HHS · T32 DK007245 · United States

NIDDK NIH HHS · 5P60 DK20572 · United States

NIDDK NIH HHS · R01-DK51563 · United States

NIDDK NIH HHS · T32-DK07245 · United States

External Links

PubMed source DOI: 10.1126/science.289.5481.950 View journal details

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Inhibition of adipogenesis by Wnt signaling.

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