Department of Physiology, Monash University, Clayton, Victoria, Australia.
Mol Cell Endocrinol. 2013 Feb 25;366(2):215-23. doi: 10.1016/j.mce.2012.06.012. Epub 2012 Jul 9.
This review highlights recent advances in the hormonal control of hypothalamic AMPK activity and the impact on appetite and energy metabolism. AMPK is an intracellular energy sensor that switches off ATP-consuming pathways and switches on ATP-producing pathways such as glucose uptake and fatty acid oxidation. In this regard, it is well positioned to respond to dynamic changes in metabolic state and nutritional over- or under-supply. Within the hypothalamus, AMPK responds to peripheral hormones that convey metabolic information based on increased plasma concentrations. For example, negative energy balance increases plasma ghrelin concentrations, increases hypothalamic AMPK and drives food intake. Conversely, plasma leptin concentrations are secreted in proportion to adipose levels and leptin suppresses hypothalamic AMPK activity and restricts food intake. This review explains that hypothalamic AMPK mediates neuroendocrine feedback control of energy metabolism. A current working model suggests that endocrine feedback influences hypothalamic AMPK via a number of mechanisms designed to shift an organism from negative to neutral energy balance. These mechanisms include (1) ghrelin stimulation of AMPK in NPY/AgRP in the arcuate nucleus (2) ghrelin stimulation of AMPK in the ventromedial hypothalamic nucleus, (3) a novel ghrelin-stimulated AMPK-dependent presynaptic mechanism that sustains AgRP neuron firing via a local synaptic memory system, (4) adiponectin stimulation of hypothalamic AMPK and (5) hypothalamic AMPK control of energy expenditure by thyroid hormone or leptin. The number of diverse mechanisms ensures hypothalamic AMPK drives the shift from negative to neutral energy balance and underscores the fundamental importance of hypothalamic AMPK to maintain neutral energy balance.
这篇综述强调了激素对下丘脑 AMPK 活性的控制作用及其对食欲和能量代谢的影响。AMPK 是一种细胞内能量传感器，它可以关闭消耗 ATP 的途径，开启产生 ATP 的途径，如葡萄糖摄取和脂肪酸氧化。在这方面，它非常适合应对代谢状态和营养供应过多或过少的动态变化。在下丘脑内，AMPK 对外周激素作出反应，这些激素根据血浆浓度的增加传递代谢信息。例如，负能平衡会增加血浆 ghrelin 浓度，增加下丘脑 AMPK，促进食欲。相反，血浆瘦素浓度与脂肪水平成正比分泌，瘦素抑制下丘脑 AMPK 活性并限制食物摄入。本综述解释了下丘脑 AMPK 介导了能量代谢的神经内分泌反馈控制。目前的工作模型表明，内分泌反馈通过多种机制影响下丘脑 AMPK，旨在使机体从负能平衡转变为中性能平衡。这些机制包括：(1)ghrelin 在弓状核 NPY/AgRP 中刺激 AMPK；(2)ghrelin 在腹内侧下丘脑核中刺激 AMPK；(3)一种新的 ghrelin 刺激 AMPK 依赖性突触前机制，通过局部突触记忆系统维持 AgRP 神经元的放电；(4)脂联素刺激下丘脑 AMPK；(5)下丘脑 AMPK 通过甲状腺激素或瘦素来控制能量消耗。多种机制的数量确保了下丘脑 AMPK 驱动从负能平衡到中性能平衡的转变，并强调了下丘脑 AMPK 对维持中性能平衡的重要性。
