Title |
Adiponectin and AdipoR1 regulate PGC-1α and mitochondria by Ca2+ and AMPK/SIRT1
|
---|---|
Published in |
Nature, April 2010
|
DOI | 10.1038/nature08991 |
Pubmed ID | |
Authors |
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, Takashi Kadowaki |
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 Ca(2+) influx by adiponectin receptor 1 (AdipoR1), which was necessary for subsequent activation of Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta), AMPK and SIRT1, increased expression and decreased acetylation of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), and increased mitochondria in myocytes. Moreover, muscle-specific disruption of AdipoR1 suppressed the adiponectin-mediated increase in intracellular Ca(2+) concentration, and decreased the activation of CaMKK, AMPK and SIRT1 by adiponectin. Suppression of AdipoR1 also resulted in decreased PGC-1alpha 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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 11 | 2% |
Japan | 10 | 2% |
United Kingdom | 6 | <1% |
Poland | 3 | <1% |
France | 2 | <1% |
Brazil | 2 | <1% |
Chile | 2 | <1% |
Italy | 1 | <1% |
South Africa | 1 | <1% |
Other | 8 | 1% |
Unknown | 591 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 138 | 22% |
Student > Ph. D. Student | 109 | 17% |
Student > Master | 77 | 12% |
Student > Doctoral Student | 48 | 8% |
Student > Bachelor | 44 | 7% |
Other | 131 | 21% |
Unknown | 90 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 227 | 36% |
Medicine and Dentistry | 123 | 19% |
Biochemistry, Genetics and Molecular Biology | 103 | 16% |
Pharmacology, Toxicology and Pharmaceutical Science | 11 | 2% |
Neuroscience | 11 | 2% |
Other | 52 | 8% |
Unknown | 110 | 17% |