Opposing Effects of Adiponectin Receptors 1 and 2 on Energy Metabolism

  1. Mikael Bjursell12,
  2. Andrea Ahnmark1,
  3. Mohammad Bohlooly-Y12,
  4. Lena William-Olsson1,
  5. Magdalena Rhedin1,
  6. Xiao-Rong Peng1,
  7. Karolina Ploj1,
  8. Anna-Karin Gerdin1,
  9. Gunnel Arnerup3,
  10. Anders Elmgren1,
  11. Anna-Lena Berg3,
  12. Jan Oscarsson124 and
  13. Daniel Lindén14
  1. 1AstraZeneca R&D, Mölndal, Sweden
  2. 2Department of Physiology/Endocrinology, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
  3. 3Safety Assessment Sweden, AstraZeneca R&D, Södertälje, Sweden
  4. 4Wallenberg Laboratory for Cardiovascular Research, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
  1. Address correspondence and reprint requests to Daniel Lindén, AstraZeneca R&D, Department of Integrative Pharmacology, SE-431 83 Mölndal, Sweden. E-mail: daniel.linden{at}astrazeneca.com

Abstract

The adipocyte-derived hormone adiponectin regulates glucose and lipid metabolism and influences the risk for developing obesity, type 2 diabetes, and cardiovascular disease. Adiponectin binds to two different seven-transmembrane domain receptors termed AdipoR1 and AdipoR2. To study the physiological importance of these receptors, AdipoR1 gene knockout mice (AdipoR1−/−) and AdipoR2 gene knockout mice (AdipoR2−/−) were generated. AdipoR1−/− mice showed increased adiposity associated with decreased glucose tolerance, spontaneous locomotor activity, and energy expenditure. However, AdipoR2−/− mice were lean and resistant to high-fat diet–induced obesity associated with improved glucose tolerance and higher spontaneous locomotor activity and energy expenditure and reduced plasma cholesterol levels. Thus, AdipoR1 and AdipoR2 are clearly involved in energy metabolism but have opposing effects.

Footnotes

  • Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db06-1432.

    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 December 11, 2006.
    • Received October 11, 2006.
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