Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase
Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase
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DOI：
10.1038/nm788
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发表时间：
2002-11-01
期刊：
影响因子：
82.9
通讯作者：
Kadowaki, T
中科院分区：
文献类型：
--
作者：
Yamauchi, T;Kamon, J;Kadowaki, T
脂联素（Adiponectin，Ad）是脂肪细胞分泌的一种激素，调节能量平衡和糖脂代谢。然而，介导Ad代谢作用的信号通路仍然很难确定。在这里，我们表明，磷酸化和激活的5 '-AMP-激活的蛋白激酶（AMPK）的刺激与球状和全长Ad在骨骼肌和只有全长Ad在肝脏。与其AMPK的激活平行，Ad刺激乙酰辅酶A羧化酶（ACC）的磷酸化、脂肪酸氧化、肌细胞中葡萄糖摄取和乳酸产生、ACC的磷酸化和参与肝脏中糖原合成的分子的减少，以及体内葡萄糖水平的降低。通过显性负突变体阻断AMPK激活可以抑制这些效应中的每一种，这表明Ad对葡萄糖利用和脂肪酸氧化的刺激是通过AMPK的激活发生的。我们的数据可能提供一个新的范例，脂肪细胞衍生的抗糖尿病激素，广告，激活AMPK，从而直接调节葡萄糖代谢和胰岛素敏感性在体外和体内。
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.