Complex multicellular organisms require a coordinated response from multiple tissues to maintain whole-body homeostasis in the face of energetic stressors such as fasting, cold, and exercise. It is also essential that energy is stored efficiently with feeding and the chronic nutrient surplus that occurs with obesity. Mammals have adapted several endocrine signals that regulate metabolism in response to changes in nutrient availability and energy demand. These include hormones altered by fasting and refeeding including insulin, glucagon, glucagon-like peptide-1, catecholamines, ghrelin, and fibroblast growth factor 21; adipokines such as leptin and adiponectin; cell stress-induced cytokines like tumor necrosis factor alpha and growth differentiating factor 15, and lastly exerkines such as interleukin-6 and irisin. Over the last 2 decades, it has become apparent that many of these endocrine factors control metabolism by regulating the activity of the AMPK (adenosine monophosphate-activated protein kinase). AMPK is a master regulator of nutrient homeostasis, phosphorylating over 100 distinct substrates that are critical for controlling autophagy, carbohydrate, fatty acid, cholesterol, and protein metabolism. In this review, we discuss how AMPK integrates endocrine signals to maintain energy balance in response to diverse homeostatic challenges. We also present some considerations with respect to experimental design which should enhance reproducibility and the fidelity of the conclusions.

中文翻译：

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AMPK 和代谢的内分泌控制。

复杂的多细胞生物体需要多个组织的协调反应，以在面对禁食、寒冷和运动等能量压力源时维持全身稳态。通过喂养和肥胖引起的长期营养过剩来有效储存能量也很重要。哺乳动物已经适应了几种调节新陈代谢的内分泌信号，以响应营养物质可用性和能量需求的变化。这些包括因禁食和重新进食而改变的激素，包括胰岛素、胰高血糖素、胰高血糖素样肽-1、儿茶酚胺、生长素释放肽和成纤维细胞生长因子 21；脂肪因子，例如瘦素和脂联素；细胞应激诱导的细胞因子，如肿瘤坏死因子 α 和生长分化因子 15，最后是运动因子，如白细胞介素 6 和鸢尾素。在过去的 20 年里，我们已经发现许多内分泌因子通过调节 AMPK（腺苷单磷酸激活蛋白激酶）的活性来控制代谢。AMPK 是营养稳态的主要调节因子，可磷酸化 100 多种不同的底物，这些底物对于控制自噬、碳水化合物、脂肪酸、胆固醇和蛋白质代谢至关重要。在这篇综述中，我们讨论了 AMPK 如何整合内分泌信号来维持能量平衡，以应对不同的稳态挑战。我们还提出了一些有关实验设计的考虑因素，这些考虑因素应提高结论的可重复性和保真度。