Adiponectin and AdipoR1 regulate PGC-1α and mitochondria by Ca2+ and AMPK/SIRT1

Masato Iwabu, Toshimasa Yamauchi (), Miki Okada-Iwabu, Koji Sato, Tatsuro Nakagawa, Masaaki Funata, Mamiko Yamaguchi, Shigeyuki Namiki, Ryo Nakayama, Mitsuhisa Tabata, Hitomi Ogata, Naoto Kubota, Iseki Takamoto, Yukiko K. Hayashi, Naoko Yamauchi, Hironori Waki, Masashi Fukayama, Ichizo Nishino, Kumpei Tokuyama, Kohjiro Ueki, Yuichi Oike, Satoshi Ishii, Kenzo Hirose, Takao Shimizu, Kazushige Touhara and Takashi Kadowaki ()
Additional contact information
Masato Iwabu: Graduate School of Medicine
Toshimasa Yamauchi: Graduate School of Medicine
Miki Okada-Iwabu: Graduate School of Medicine
Koji Sato: Graduate School of Agricultural and Life Sciences, The University of Tokyo
Tatsuro Nakagawa: The University of Tokyo
Masaaki Funata: Graduate School of Medicine
Mamiko Yamaguchi: Graduate School of Medicine
Shigeyuki Namiki: Graduate School of Medicine
Ryo Nakayama: Graduate School of Medicine
Mitsuhisa Tabata: Graduate School of Medical Sciences, Kumamoto University
Hitomi Ogata: Graduate School of Comprehensive Human Sciences, University of Tsukuba
Naoto Kubota: Graduate School of Medicine
Iseki Takamoto: Graduate School of Medicine
Yukiko K. Hayashi: National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan
Naoko Yamauchi: Graduate School of Medicine
Hironori Waki: Graduate School of Medicine
Masashi Fukayama: Graduate School of Medicine
Ichizo Nishino: National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan
Kumpei Tokuyama: Graduate School of Comprehensive Human Sciences, University of Tsukuba
Kohjiro Ueki: Graduate School of Medicine
Yuichi Oike: Graduate School of Medical Sciences, Kumamoto University
Satoshi Ishii: Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Kenzo Hirose: Graduate School of Medicine
Takao Shimizu: Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Kazushige Touhara: Graduate School of Agricultural and Life Sciences, The University of Tokyo
Takashi Kadowaki: Graduate School of Medicine

Nature, 2010, vol. 464, issue 7293, 1313-1319

Abstract: Abstract Adiponectin is an anti-diabetic adipokine. Its receptors possess a seven-transmembrane topology with the amino terminus located intracellularly, which is the opposite of G-protein-coupled receptors. Here we provide evidence that adiponectin induces extracellular Ca2+ influx by adiponectin receptor 1 (AdipoR1), which was necessary for subsequent activation of Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ), AMPK and SIRT1, increased expression and decreased acetylation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and increased mitochondria in myocytes. Moreover, muscle-specific disruption of AdipoR1 suppressed the adiponectin-mediated increase in intracellular Ca2+ concentration, and decreased the activation of CaMKK, AMPK and SIRT1 by adiponectin. Suppression of AdipoR1 also resulted in decreased PGC-1α expression and deacetylation, decreased mitochondrial content and enzymes, decreased oxidative type I myofibres, and decreased oxidative stress-detoxifying enzymes in skeletal muscle, which were associated with insulin resistance and decreased exercise endurance. Decreased levels of adiponectin and AdipoR1 in obesity may have causal roles in mitochondrial dysfunction and insulin resistance seen in diabetes.

Date: 2010
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature08991 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:464:y:2010:i:7293:d:10.1038_nature08991

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature08991

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().