Adiponectin stimulates AMP-Activated protein kinase in the hypothalamus and increases food intake
Adiponectin stimulates AMP-Activated protein kinase in the hypothalamus and increases food intake
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DOI：
10.1016/j.cmet.2007.06.003
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发表时间：
2007-07-01
期刊：
影响因子：
29
通讯作者：
Kadowaki, Takashi
中科院分区：
文献类型：
--
作者：
Kubota, Naoto;Yano, Wataru;Kadowaki, Takashi
脂联素可通过激活外周组织中的腺苷酸活化蛋白激酶（AMPK），刺激脂肪酸氧化，增强胰岛素敏感性。然而，脂联素在中枢神经系统中的作用仍然知之甚少。在这里，我们表明，脂联素增强AMPK活性在弓状下丘脑（ARH）通过其受体AdipoR1刺激食物摄入，这种刺激的食物摄入的脂联素减弱显性负AMPK表达的方舟此外，脂联素还减少能量消耗。脂联素缺乏小鼠ARH中AMPK磷酸化水平降低，食物摄入减少，能量消耗增加，表现出对高脂饮食诱导的肥胖的抵抗力。血清和脑脊液中脂联素水平和AdipoR1的表达在禁食期间增加，再喂养后减少。我们的结论是，脂联素刺激食物的摄入量，并通过其在中枢神经系统的影响，减少能量消耗禁食期间。
Adiponectin has been shown to stimulate fatty acid oxidation and enhance insulin sensitivity through the activation of AMP-activated protein kinase (AMPK) in the peripheral tissues. The effects of adiponectin in the central nervous system, however, are still poorly understood. Here, we show that adiponectin enhances AMPK activity in the arcuate hypothalamus (ARH) via its receptor AdipoR1 to stimulate food intake; this stimulation of food intake by adiponectin was attenuated by dominant-negative AMPK expression in the ARK Moreover, adiponectin also decreased energy expenditure. Adiponectin-deficient mice showed decreased AMPK phosphorylation in the ARH, decreased food intake, and increased energy expenditure, exhibiting resistance to high-fat-diet-induced obesity. Serum and cerebrospinal fluid levels of adiponectin and expression of AdipoR1 in the ARH were increased during fasting and decreased after refeeding. We conclude that adiponectin stimulates food intake and decreases energy expenditure during fasting through its effects in the central nervous system.