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Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
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Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
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Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
Journal Article

Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth

2008
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Overview
Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth Nora Klöting 1 , Linda Koch 2 , Thomas Wunderlich 2 , Matthias Kern 1 , Karen Ruschke 1 , Wilhelm Krone 3 , Jens C. Brüning 2 and Matthias Blüher 1 3 4 1 Department of Medicine, University of Leipzig, Leipzig, Germany 2 Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne and Center of Molecular Medicine Cologne, Cologne, Germany 3 Department of Internal Medicine II, University of Cologne and Center of Molecular Medicine Cologne, Cologne, Germany 4 Interdisciplinary 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-1R aP2Cre 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-1R aP2Cre 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 Published ahead of print at http://diabetes.diabetesjournals.org on 28 April 2008. N.K. and L.K. contributed equally to this work. 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. 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. Accepted April 22, 2008. Received October 29, 2007. DIABETES