• DOI:10.1038/nm788
• Corpus ID: 13051644

Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase

@article{Yamauchi2002AdiponectinSG,
  title={Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase},
  author={Toshimasa Yamauchi and Junji Kamon and Yasuhiko Minokoshi and Y. Ito and Hironori Waki and Satoshi Uchida and Shigeo Yamashita and Mitsuhiko Noda and Shunbun Kita and Kohjiro Ueki and Kazuhiro Eto and Yauso Akanuma and Philippe Froguel and Fabienne Foufelle and Pascal Ferr{\'e} and David Carling and Satoshi Kimura and Ryozo Nagai and Barbara B. Kahn and Takashi Kadowaki},
  journal={Nature Medicine},
  year={2002},
  volume={8},
  pages={1288-1295}
}

• T. Yamauchi, J. Kamon, +17 authors T. Kadowaki
• Published 30 October 2002
• Biology, Chemistry
• Nature Medicine

Adiponectin (Ad) is a hormone secreted by adipocytes that regulates energy homeostasis and glucose and lipid metabolism. However, the signaling pathways that mediate the metabolic effects of Ad remain poorly identified. Here we show that phosphorylation and activation of the 5′-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length Ad in skeletal muscle and only with full-length Ad in the liver. In parallel with its activation of AMPK, Ad stimulates phosphorylation of acetyl coenzyme A carboxylase (ACC), fatty-acid oxidation, glucose uptake and lactate production in myocytes, phosphorylation of ACC and reduction of molecules involved in gluconeogenesis in the liver, and reduction of glucose levels in vivo. Blocking AMPK activation by dominant-negative mutant inhibits each of these effects, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK. Our data may provide a novel paradigm that an adipocyte-derived antidiabetic hormone, Ad, activates AMPK, thereby directly regulating glucose metabolism and insulin sensitivity in vitro and in vivo.