Journal ArticleDOI
Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase
Toshimasa Yamauchi,Junji Kamon,Yasuhiko Minokoshi,Yoichi M. Ito,Hironori Waki,S. Uchida,Shigeo Yamashita,Mitsuhiko Noda,Shunbun Kita,K Ueki,Koji Eto,Y. Akanuma,Philippe Froguel,Fabienne Foufelle,Pascal Ferré,David Carling,Shigeko Kimura,Ryozo Nagai,Barbara B. Kahn,Takashi Kadowaki +19 more
TLDR
It is shown 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- lengths Ad in the liver, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK.Abstract:
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.read more
Citations
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Journal ArticleDOI
Adipokines in inflammation and metabolic disease
TL;DR: The role of adipokines in inflammatory responses is focused on and their potential as regulators of metabolic function is discussed.
Journal ArticleDOI
Adipose tissue as an endocrine organ.
TL;DR: These proteins commonly known as adipokines are central to the dynamic control of energy metabolism, communicating the nutrient status of the organism with the tissues responsible for controlling both energy intake and expenditure as well as insulin sensitivity.
Journal ArticleDOI
Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
Toshimasa Yamauchi,Junji Kamon,Yusuke Ito,Atsushi Tsuchida,Takehiko Yokomizo,Takehiko Yokomizo,Shunbun Kita,Takuya Sugiyama,Makoto Miyagishi,Makoto Miyagishi,Kazuo Hara,Masaki Tsunoda,Koji Murakami,Toshiaki Ohteki,S. Uchida,Sato Takekawa,Hironori Waki,Nelson H. Tsuno,Yoichi Shibata,Yasuo Terauchi,Philippe Froguel,Kazuyuki Tobe,Shigeo Koyasu,Kazunari Taira,Kazunari Taira,Toshio Kitamura,Takao Shimizu,Takao Shimizu,Ryozo Nagai,Takashi Kadowaki +29 more
TL;DR: The cloning of complementary DNAs encoding adiponectin receptors 1 and 2 by expression cloning supports the conclusion that they serve as receptors for globular and full-length adiponECTin, and that they mediate increased AMP kinase and PPAR-α ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectionin.
Journal ArticleDOI
Adipocytokines: mediators linking adipose tissue, inflammation and immunity.
TL;DR: Several adipocytokines have a central role in the regulation of insulin resistance, as well as many aspects of inflammation and immunity, and understanding this rapidly growing family of mainly adipocyte-derived mediators might be of importance in the development of new therapies for obesity-associated diseases.
Journal ArticleDOI
AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism
TL;DR: Through signaling, metabolic, and gene expression effects, AMPK enhances insulin sensitivity and fosters a metabolic milieu that may reduce the risk for obesity and type 2 diabetes.
References
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Role of AMP-activated protein kinase in mechanism of metformin action
Gaochao Zhou,Robert W. Myers,Ying Li,Yuli Chen,Xiaolan Shen,Judy Fenyk-Melody,Margaret Wu,John Ventre,Thomas W. Doebber,Nobuharu Fujii,Nicolas Musi,Michael F. Hirshman,Laurie J. Goodyear,David E. Moller +13 more
TL;DR: It is reported that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed.
Journal ArticleDOI
Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.
Yukio Arita,Shinji Kihara,Noriyuki Ouchi,Masahiko Takahashi,Kazuhisa Maeda,Jun-ichiro Miyagawa,Kikuko Hotta,Iichiro Shimomura,Tadashi Nakamura,Koji Miyaoka,Hiroshi Kuriyama,Makoto Nishida,Shizuya Yamashita,Kosaku Okubo,Kenji Matsubara,Masahiro Muraguchi,Yasuichi Ohmoto,Tohru Funahashi,Yuji Matsuzawa +18 more
TL;DR: Plasma concentrations of adiponectin in obese subjects were significantly lower than those in non-obese subjects, although adip onectin is secreted only from adipose tissue.
Journal ArticleDOI
The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity
Toshimasa Yamauchi,Junji Kamon,Hironori Waki,Yasuo Terauchi,Naoto Kubota,Kazuo Hara,Y. Mori,Tomohiro Ide,Kouji Murakami,Nobuyo Tsuboyama-Kasaoka,Osamu Ezaki,Y. Akanuma,Oksana Gavrilova,Charles Vinson,Marc L. Reitman,Hiroyuki Kagechika,Koichi Shudo,Madoka Yoda,Yasuko Nakano,Kazuyuki Tobe,R. Nagai,Shigeko Kimura,Motowo Tomita,Philippe Froguel,Takashi Kadowaki +24 more
TL;DR: It is concluded that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy and that the replenishment of adiponECTin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
Journal ArticleDOI
Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor.
TL;DR: The results suggest that the physiologic role of PPAR gamma 2 is to regulate development of the adipose lineage in response to endogenous lipid activators and that this factor may serve to link the process of adipocyte differentiation to systemic lipid metabolism.
Journal ArticleDOI
Obesity and insulin resistance
Barbara B. Kahn,Jeffrey S. Flier +1 more
TL;DR: Recent progress in understanding of the adipo-insulin axis is reviewed, areas of controversy or uncertainty are highlighted, and approaches to clarifying the unresolved issues are suggested.
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