Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
- Nora Klöting1,
- Linda Koch2,
- Thomas Wunderlich2,
- Matthias Kern1,
- Karen Ruschke1,
- Wilhelm Krone3,
- Jens C. Brüning2 and
- Matthias Blüher134
- 1Department of Medicine, University of Leipzig, Leipzig, Germany
- 2Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne and Center of Molecular Medicine Cologne, Cologne, Germany
- 3Department of Internal Medicine II, University of Cologne and Center of Molecular Medicine Cologne, Cologne, Germany
- 4Interdisciplinary Center for Clinical Research (IZKF), Leipzig, Germany
- Corresponding authors: Jens C. Brüning, jens.bruening{at}uni-koeln.de; Matthias Blüher, bluma{at}medizin.uni-leipzig.de
Abstract
OBJECTIVE—IGF-1 and the IGF-1 receptor (IGF-1R) have been implicated in the regulation of adipocyte differentiation and lipid accumulation in vitro.
RESEARCH DESIGN AND METHODS—To investigate the role of IGF-1 receptor in vivo, we have inactivated the Igf-1r gene in adipose tissue (IGF-1RaP2Cre mice) using conditional gene targeting strategies.
RESULTS—Conditional IGF-1R inactivation resulted in increased adipose tissue mass with a predominantly increased lipid accumulation in epigonadal fat pads. However, insulin-stimulated glucose uptake into adipocytes was unaffected by the deletion of the IGF-1R. Surprisingly, IGF-1RaP2Cre mice exhibited markedly increased somatic growth in the presence of elevated IGF-1 serum concentrations, and IGF-1 mRNA expression was significantly increased in liver and adipose tissue. IGF-1 stimulation of wild-type adipocytes significantly decreased IGF-1 mRNA expression, whereas the opposite effect was observed in IGF-1R–deficient adipocytes.
CONCLUSIONS—IGF-1R signaling in adipocytes does not appear to be crucial for the development and differentiation of adipose tissue in vivo, but we identified a negative IGF-1R–mediated feedback mechanism of IGF-1 on its own gene expression in adipocytes, indicating an unexpected role for adipose tissue IGF-1 signaling in the regulation of IGF-1 serum concentrations in control of somatic growth.
Footnotes
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Published ahead of print at http://diabetes.diabetesjournals.org on 28 April 2008.
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N.K. and L.K. contributed equally to this work.
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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.
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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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- Accepted April 22, 2008.
- Received October 29, 2007.
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