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Cloning of adiponectin receptors that mediate antidiabetic metabolic effects

Author

Listed:
  • Toshimasa Yamauchi

    (University of Tokyo
    CREST of Japan Science and Technology Corporation)

  • Junji Kamon

    (University of Tokyo
    Nissan Chemical Industries)

  • Yusuke Ito

    (University of Tokyo)

  • Atsushi Tsuchida

    (University of Tokyo)

  • Takehiko Yokomizo

    (University of Tokyo
    CREST and PRESTO of JST)

  • Shunbun Kita

    (University of Tokyo)

  • Takuya Sugiyama

    (University of Tokyo)

  • Makoto Miyagishi

    (University of Tokyo
    Gene Function Research Center, National Institute of AIST)

  • Kazuo Hara

    (University of Tokyo
    CREST of Japan Science and Technology Corporation)

  • Masaki Tsunoda

    (Central Research Laboratories, Kyorin Pharmaceutical)

  • Koji Murakami

    (Central Research Laboratories, Kyorin Pharmaceutical)

  • Toshiaki Ohteki

    (CREST of Japan Science and Technology Corporation
    Keio University School of Medicine)

  • Shoko Uchida

    (University of Tokyo)

  • Sato Takekawa

    (University of Tokyo)

  • Hironori Waki

    (University of Tokyo
    CREST of Japan Science and Technology Corporation)

  • Nelson H. Tsuno

    (University of Tokyo)

  • Yoichi Shibata

    (University of Tokyo)

  • Yasuo Terauchi

    (University of Tokyo
    CREST of Japan Science and Technology Corporation)

  • Philippe Froguel

    (Institute of Biology-CNRS, Pasteur Institute of Lille, UPRES)

  • Kazuyuki Tobe

    (University of Tokyo
    CREST of Japan Science and Technology Corporation)

  • Shigeo Koyasu

    (CREST of Japan Science and Technology Corporation
    Keio University School of Medicine)

  • Kazunari Taira

    (University of Tokyo
    Gene Function Research Center, National Institute of AIST)

  • Toshio Kitamura

    (University of Tokyo)

  • Takao Shimizu

    (University of Tokyo
    CREST and PRESTO of JST)

  • Ryozo Nagai

    (University of Tokyo)

  • Takashi Kadowaki

    (University of Tokyo
    CREST of Japan Science and Technology Corporation)

Abstract

Corrigendum (2004) 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.

Suggested Citation

  • Toshimasa Yamauchi & Junji Kamon & Yusuke Ito & Atsushi Tsuchida & Takehiko Yokomizo & Shunbun Kita & Takuya Sugiyama & Makoto Miyagishi & Kazuo Hara & Masaki Tsunoda & Koji Murakami & Toshiaki Ohteki, 2003. "Cloning of adiponectin receptors that mediate antidiabetic metabolic effects," Nature, Nature, vol. 423(6941), pages 762-769, June.
    • Handle: RePEc:nat:nature:v:423:y:2003:i:6941:d:10.1038_nature01705
    DOI: 10.1038/nature01705
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    Citations

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    Cited by:

    1. Lucia Balazova & Miroslav Balaz & Carla Horvath & Áron Horváth & Caroline Moser & Zuzana Kovanicova & Adhideb Ghosh & Umesh Ghoshdastider & Vissarion Efthymiou & Elke Kiehlmann & Wenfei Sun & Hua Dong, 2021. "GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Mario Ruiz & Ranjan Devkota & Dimitra Panagaki & Per-Olof Bergh & Delaney Kaper & Marcus Henricsson & Ali Nik & Kasparas Petkevicius & Johanna L. Höög & Mohammad Bohlooly-Y & Peter Carlsson & Jan Boré, 2022. "Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. Jin-Hyuck Jeong & Jun-Seok Han & Youngae Jung & Seung-Min Lee & So-Hyun Park & Mooncheol Park & Min-Gi Shin & Nami Kim & Mi Sun Kang & Seokho Kim & Kwang-Pyo Lee & Ki-Sun Kwon & Chun-A. Kim & Yong Ryo, 2023. "A new AMPK isoform mediates glucose-restriction induced longevity non-cell autonomously by promoting membrane fluidity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Shixuan Liu & Camille Ezran & Michael F. Z. Wang & Zhengda Li & Kyle Awayan & Jonathan Z. Long & Iwijn De Vlaminck & Sheng Wang & Jacques Epelbaum & Christin S. Kuo & Jérémy Terrien & Mark A. Krasnow , 2024. "An organism-wide atlas of hormonal signaling based on the mouse lemur single-cell transcriptome," Nature Communications, Nature, vol. 15(1), pages 1-27, December.
    5. Rui Wang & Youwei Chen & Jiazhen Han & Huikang Ye & Huiran Yang & Qianyan Li & Yizhen He & Boyu Ma & Junjie Zhang & Yanli Ge & Zhe Wang & Bo Sun & Huahua Liu & Liming Cheng & Zhirong Wang & Gufa Lin, 2024. "Selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 as a rapid-acting therapy for advanced acute liver failure," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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