Autocrine IGF-1 action in adipocytes controls systemic IGF-1 concentrations and growth

  1. Nora Klöting, PhD1,
  2. Linda Koch2,
  3. Thomas Wunderlich, PhD2,
  4. Matthias Kern1,
  5. Karen Ruschke, PhD1,
  6. Wilhelm Krone, MD3,
  7. Jens C. Brüning, MD (jens.bruening{at}uni-koeln.de)2 and
  8. Matthias Blüher, MD (bluma{at}medizin.uni-leipzig.de)1,,3
  1. 1Department of Medicine, University of Leipzig, Leipzig, Germany
  2. 2Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne and Center of Molecular Medicine Cologne (CMMC), Cologne, Germany
  3. 3Department of Internal Medicine II, University of Cologne and Center of Molecular Medicine Cologne (CMMC), Cologne, Germany

    Abstract

    Objective: Insulin-like growth factor-1 (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-1 receptor 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, while the opposite effect was obeserved in IGF-1R deficient adipocytes.

    Conclusions: IGF-1 receptor 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-1 receptor-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

      • Received October 29, 2007.
      • Accepted April 22, 2008.

    This Article

    1. Published online before print April 28, 2008, doi: 10.2337/db07-1538
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