Centre for Metabolism Obesity and Diabetes Research, Hamilton, ON L8S 4L8, Canada.
Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Endocr Rev. 2023 Sep 15;44(5):910-933. doi: 10.1210/endrev/bnad012.
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.
复杂的多细胞生物需要多个组织协调响应，以在面对能量应激源（如禁食、寒冷和运动）时维持全身的内稳态。在进食时有效地储存能量以及在肥胖时发生的慢性营养过剩也是至关重要的。哺乳动物已经适应了几种内分泌信号，这些信号可以根据营养物质可用性和能量需求的变化来调节代谢。这些信号包括受禁食和再喂养影响的激素，如胰岛素、胰高血糖素、胰高血糖素样肽-1、儿茶酚胺、胃饥饿素和成纤维细胞生长因子 21；脂肪因子，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，以及最后一类激素细胞因子，如白细胞介素-6 和鸢尾素。在过去的 20 年中，人们已经清楚地认识到，许多这些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 是营养物质稳态的主要调节剂，磷酸化超过 100 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，以响应各种稳态挑战来维持能量平衡。我们还提出了一些关于实验设计的考虑因素，这些因素应该可以提高实验的可重复性和结论的准确性。
