AMP-activated protein kinase plays a role in the control of food intake
AMP-activated protein kinase plays a role in the control of food intake
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DOI：
10.1074/jbc.c300557200
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发表时间：
2004-03-26
影响因子：
4.8
通讯作者：
Small, CJ
中科院分区：
文献类型：
--
作者：
Andersson, U;Filipsson, K;Small, CJ
AMP活化蛋白激酶（AMPK）是蛋白激酶级联的下游组分，其充当维持细胞内能量平衡的细胞内能量传感器。瘦素和脂联素激活AMPK改变肌肉和肝脏中的代谢途径的发现为外周组织中的这种作用提供了直接证据。下丘脑是食物摄入和能量平衡的关键调节器，响应于外周激素如瘦素、肽YY-（3-36）和生长素释放肽来协调身体肥胖和营养状态。到目前为止，还没有关于AMPK在下丘脑中的激素调节或其在控制食物摄入中的潜在作用的报道。在这里，我们表明，反调节激素参与食欲控制调节AMPK活性和药理学激活AMPK在下丘脑增加食物摄入。体内施用瘦素，导致食物摄入减少，降低下丘脑AMPK活性。相比之下，体内注射生长素释放肽，增加食物摄入，刺激下丘脑中的AMPK活性。与饥饿素的作用一致，将5-氨基-4-咪唑甲酰胺核苷（AMPK的药理学激活剂）注射到第三脑室内或直接注射到下丘脑室旁核中显着增加了食物摄入量。这些结果表明AMPK在下丘脑中受调节食物摄入的激素调节。此外，下丘脑中AMPK的直接药理学激活足以增加食物摄入。这些发现表明AMPK在摄食调节中起作用，并确定AMPK作为抗肥胖药物的新靶点。
AMP-activated protein kinase ( AMPK) is the downstream component of a protein kinase cascade that acts as an intracellular energy sensor maintaining the energy balance within the cell. The finding that leptin and adiponectin activate AMPK to alter metabolic pathways in muscle and liver provides direct evidence for this role in peripheral tissues. The hypothalamus is a key regulator of food intake and energy balance, coordinating body adiposity and nutritional state in response to peripheral hormones, such as leptin, peptide YY-(3-36), and ghrelin. To date the hormonal regulation of AMPK in the hypothalamus, or its potential role in the control of food intake, have not been reported. Here we demonstrate that counter-regulatory hormones involved in appetite control regulate AMPK activity and that pharmacological activation of AMPK in the hypothalamus increases food intake. In vivo administration of leptin, which leads to a reduction in food intake, decreases hypothalamic AMPK activity. By contrast, injection of ghrelin in vivo, which increases food intake, stimulates AMPK activity in the hypothalamus. Consistent with the effect of ghrelin, injection of 5-amino-4-imidazole carboxamide riboside, a pharmacological activator of AMPK, into either the third cerebral ventricle or directly into the paraventricular nucleus of the hypothalamus significantly increased food intake. These results suggest that AMPK is regulated in the hypothalamus by hormones which regulate food intake. Furthermore, direct pharmacological activation of AMPK in the hypothalamus is sufficient to increase food intake. These findings demonstrate that AMPK plays a role in the regulation of feeding and identify AMPK as a novel target for anti-obesity drugs.