Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30)1,2,3,4 is a hormone secreted by adipocytes that acts as an antidiabetic5,6,7,8,9,10,11,12 and anti-atherogenic8,12,13 adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes2. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice5,6,7. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes8,9. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase10,11 and PPAR-α5,6,12. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning14,15,16. AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. These two adiponectin receptors are predicted to contain seven transmembrane domains, but to be structurally and functionally distinct from G-protein-coupled receptors17,18,19. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA20 supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase10,11 and PPAR-α ligand activities12, as well as fatty-acid oxidation and glucose uptake by adiponectin.
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We are grateful to K. Kirii, A. Itoh, A. Okano, T. Nagano and S. Nakamura for their technical assistance. This work was supported by a Grant-in-Aid for Creative Scientific Research from the Japan Society for the Promotion of Science (to T.K.), and by Health Science Research Grants (Research on Human Genome and Gene Therapy) from the Ministry of Health and Welfare (to T.K.).
The authors declare that they have no competing financial interests.
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