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

  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},
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… 
Chronic Hexosamine Flux Stimulates Fatty Acid Oxidation by Activating AMP-activated Protein Kinase in Adipocytes*
Chronic high hexosamine flux stimulates fatty acid oxidation by activating AMPK in adipocytes, in part through O-linked glycosylation, demonstrating that AMPK is regulated by the HBP.
Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation.
The role of AMPK in adipose tissue is discussed, focussing on the regulation of carbohydrate and lipid metabolism, adipogenesis and pro-inflammatory pathways in physiological and pathophysiological conditions.
Functions of AMP‐activated protein kinase in adipose tissue
Since fatty acids have a key role in insulin resistance, especially in muscles, activating AMPK in adipose tissue might be found to be beneficial in insulin‐resistant states, particularly as AMPK activation also reduces cytokine secretion in adipocytes.
Adiponectin Increases Fatty Acid Oxidation in Skeletal Muscle Cells by Sequential Activation of AMP-Activated Protein Kinase, p38 Mitogen-Activated Protein Kinase, and Peroxisome Proliferator–Activated Receptor α
It is suggested that adiponectin stimulates fatty acid oxidation in muscle cells by the sequential activation of AMPK, p38 MAPK, and PPARα.
Impaired activation of AMP-kinase and fatty acid oxidation by globular adiponectin in cultured human skeletal muscle of obese type 2 diabetics.
Reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
AMP-activated protein kinase in the heart: role in cardiac glucose and fatty acid metabolism
This review focuses on the emerging information regarding the regulation of AMPK, its role in cardiac glucose and fatty acid metabolism and its influence on cell death.
AMP‐activated protein kinase: role in metabolism and therapeutic implications
Evidence that pharmacological activation of AMPK in vivo improves blood glucose homeostasis, cholesterol concentrations and blood pressure in insulin‐resistant rodents, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes, ischaemic heart disease and other metabolic diseases.
Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes.
Inhibition of AMP kinase activation using two pharmacological inhibitors completely abrogated the increase in glucose uptake stimulated by globular adiponectin, indicating that AMP Kinase is integrally involved in the adiponECTin signal transduction pathway.


Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
It is shown that leptin selectively stimulates phosphorylation and activation of the α2 catalytic subunit of AMPK (α2 AMPK) in skeletal muscle, thus establishing a previously unknown signalling pathway for leptin, and identifying AMPK as a principal mediator of the effects of leptin on fatty-acid metabolism in muscle.
AMP-activated protein kinase, a metabolic master switch: possible roles in Type 2 diabetes.
  • W. Winder, D. Hardie
  • Biology, Medicine
    American journal of physiology. Endocrinology and metabolism
  • 1999
Increased recruitment of the AMPK signaling system, either by exercise or pharmaceutical activators, may be effective in correcting insulin resistance in patients with forms of impaired glucose tolerance and Type 2 diabetes resulting from defects in the insulin signaling cascade.
Role of AMP-activated protein kinase in mechanism of metformin action.
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.
Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism.
The activation of AMPK may be a common mechanism leading to insulin-independent glucose transport in skeletal muscle under conditions of metabolic stress, and this hypothesis is tested under several conditions that evoke metabolic stress accompanied by intracellular fuel depletion.
Characterization of the Role of AMP-Activated Protein Kinase in the Regulation of Glucose-Activated Gene Expression Using Constitutively Active and Dominant Negative Forms of the Kinase
The results suggest that AMPK is involved in the inhibition of glucose-activated gene expression but not in the induction pathway, and demonstrates that the two mutants generated will provide valuable tools for studying the wider physiological role of AMPK.
The Anti-diabetic Drugs Rosiglitazone and Metformin Stimulate AMP-activated Protein Kinase through Distinct Signaling Pathways*
It is shown that incubation of muscle cells with the thiazolidinedione, rosiglitazone, leads to a dramatic increase in this ratio with the concomitant activation of AMPK, which raises the possibility that a number of the beneficial effects of the th Diazolidinediones could be mediated via activated AMPK.
Endogenous glucose production is inhibited by the adipose-derived protein Acrp30.
Results indicate that an acute increase in circulating Acrp30 levels lowers hepatic glucose production without affecting peripheral glucose uptake, and a moderate rise in circulating levels of the adipose-derived protein Acp30 inhibits both the expression of hepatic gluconeogenic enzymes and the rate of endogenous glucose production.
Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice.
  • J. Fruebis, T. Tsao, H. Lodish
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
Daily administration of a very low dose of gAcrp30 to mice consuming a high-fat/sucrose diet caused profound and sustainable weight reduction without affecting food intake.