Adipose Overexpression of Desnutrin Promotes Fatty Acid Use and Attenuates Diet-Induced Obesity
- Maryam Ahmadian1,
- Robin E. Duncan1,
- Krista A. Varady1,
- Danubia Frasson1,
- Marc K. Hellerstein1,
- Andreas L. Birkenfeld2,
- Varman T. Samuel2,
- Gerald I. Shulman2,
- Yuhui Wang1,
- Chulho Kang3 and
- Hei Sook Sul1
- 1Department of Nutritional Science and Toxicology, University of California, Berkeley, California;
- 2Department of Internal Medicine, Yale University, School of Medicine, New Haven, Connecticut
- 3Department of Molecular and Cell Biology, University of California, Berkeley, California.
- Corresponding author: Hei Sook Sul, hsul{at}nature.berkeley.edu.
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M.A. and R.E.D. contributed equally to this article.
Abstract
OBJECTIVE To investigate the role of desnutrin in adipose tissue triacylglycerol (TAG) and fatty acid metabolism.
RESEARCH DESIGN AND METHODS We generated transgenic mice overexpressing desnutrin (also called adipose triglyceride lipase [ATGL]) in adipocytes (aP2-desnutrin) and also performed adenoviral-mediated overexpression of desnutrin in 3T3-L1CARΔ1 adipocytes.
RESULTS aP2-desnutrin mice were leaner with decreased adipose tissue TAG content and smaller adipocyte size. Overexpression of desnutrin increased lipolysis but did not result in increased serum nonesterified fatty acid levels or ectopic TAG storage. We found increased cycling between diacylglycerol (DAG) and TAG and increased fatty acid oxidation in adipocytes from these mice, as well as improved insulin sensitivity.
CONCLUSIONS We show that by increasing lipolysis, desnutrin overexpression causes reduced adipocyte TAG content and attenuation of diet-induced obesity. Desnutrin-mediated lipolysis promotes fatty acid oxidation and re-esterification within adipocytes.
Footnotes
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D.F. is currently affiliated with the Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received November 26, 2008.
- Accepted January 5, 2009.
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Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
- © 2009 by the American Diabetes Association.
