Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic effects
- Departments of *Pediatrics,
- †Cellular and Molecular Pharmacology,
- §Medicine, and
- ¶Biochemistry and Biophysics, University of California, San Francisco, CA 94143; and
- ‡Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94143
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Contributed by Keith R. Yamamoto, August 28, 2006
Abstract
A pluripotent cell line, C3H10T1/2, is induced to undergo adipogenesis by a mixture of factors that includes a glucocorticoid such as dexamethasone. We found that expression of myostatin (MSTN), a TGF-β family member extensively studied in muscle, was induced by dexamethasone under those differentiation conditions. Moreover, MSTN could substitute for dexamethasone in the adipogenesis mixture. However, the adipocytes induced by MSTN in both cell culture and transgenic mice were small and expressed markers characteristic of immature adipocytes. These adipocytes exhibited cell-autonomous increases in insulin sensitivity and glucose oxidation. In mice, these effects produced elevated systemic insulin sensitivity and resistance to diet-induced obesity. Modulation of the final stages of adipogenesis may provide a novel approach to understanding and treating metabolic disease.
Footnotes
- ‖To whom correspondence should be addressed. E-mail: yamamoto{at}cmp.ucsf.edu
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Author contributions: B.J.F. and K.R.Y. designed research; B.J.F. and R.S.S. performed research; R.V.F. contributed new reagents/analytic tools; B.J.F. and K.R.Y. analyzed data; and B.J.F. and K.R.Y. wrote the paper.
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The authors declare no conflict of interest.
- Abbreviations:
- MSTN,
- myostatin;
- DIM,
- dexamethasone/insulin/isobutylmethylxanthine;
- MIM,
- MSTN/insulin/isobutylmethylxanthine;
- aP2,
- adipocyte P2.
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Freely available online through the PNAS open access option.
- © 2006 by The National Academy of Sciences of the USA
