Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain.
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, 15706, Spain.
Nat Rev Endocrinol. 2016 Jul;12(7):421-32. doi: 10.1038/nrendo.2016.67. Epub 2016 May 20.
AMP-activated protein kinase (AMPK) has a major role in the modulation of energy balance. AMPK is activated in conditions of low energy, increasing energy production and reducing energy consumption. The AMPK pathway is a canonical route regulating energy homeostasis by integrating peripheral signals, such as hormones and metabolites, with neuronal networks. Current evidence has implicated AMPK in the hypothalamus and hindbrain with feeding, brown adipose tissue thermogenesis and browning of white adipose tissue, through modulation of the sympathetic nervous system, as well as glucose homeostasis. Interestingly, several potential antiobesity and/or antidiabetic agents, some of which are currently in clinical use such as metformin and liraglutide, exert some of their actions by acting on AMPK. Furthermore, the orexigenic and weight-gain effects of commonly used antipsychotic drugs are also mediated by hypothalamic AMPK. Overall, this evidence suggests that hypothalamic AMPK signalling is an interesting target for drug development, but is this approach feasible? In this Review we discuss the current understanding of hypothalamic AMPK and its role in the central regulation of energy balance and metabolism.
AMP 激活的蛋白激酶（AMPK）在调节能量平衡方面起着重要作用。在能量不足的情况下，AMPK 被激活，增加能量产生，减少能量消耗。AMPK 通路是一种通过整合外周信号（如激素和代谢物）与神经元网络来调节能量稳态的经典途径。目前的证据表明，AMPK 参与了下丘脑和后脑的摄食、棕色脂肪组织产热和白色脂肪组织褐变，通过调节交感神经系统以及葡萄糖稳态。有趣的是，一些潜在的抗肥胖和/或抗糖尿病药物，其中一些如二甲双胍和利拉鲁肽目前正在临床使用，通过作用于 AMPK 发挥部分作用。此外，常用抗精神病药物的食欲亢进和体重增加作用也是通过下丘脑 AMPK 介导的。总的来说，这些证据表明，下丘脑 AMPK 信号是药物开发的一个有趣的靶点，但这种方法是否可行？在这篇综述中，我们讨论了目前对下丘脑 AMPK 的理解及其在能量平衡和代谢的中枢调节中的作用。
