School of Life Sciences, Beijing University of Chinese Medicine, Yangguang South Street, Fangshan District, Beijing, 102401, China.
Curr Drug Targets. 2022;23(11):1057-1071. doi: 10.2174/1389450123666220429082702.
Obesity and type 2 diabetes mellitus (T2DM), as common metabolic diseases, are pathologically characterized by overnutrition and insulin resistance (IR), which subsequently lead to glucose and lipid metabolism disorders. The liver, a major metabolic organ of the body, integrates hormone and metabolic signals to regulate the synthesis of lipids and glucose as well as their transport to peripheral tissues, hence playing an essential role in the development of obesity and T2DM. Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a central regulator involved in cellular and organismal metabolism in eukaryotes, which activates processes that produce ATP and diminishes its consumption. In addition, AMPK also regulates mitochondrial homeostasis and promotes autophagy, both of which are associated with the pathogenesis of IR. Therefore, increasing AMPK activity is considered a promising therapeutic strategy to prevent obesity and T2DM. In this review, we summarize the role of hepatic AMPK in obesity and T2DM and the potential of using AMPK activators as therapeutics for metabolic disorders.
肥胖症和 2 型糖尿病（T2DM）作为常见的代谢性疾病，其病理特征为营养过剩和胰岛素抵抗（IR），进而导致葡萄糖和脂质代谢紊乱。肝脏作为人体主要的代谢器官，整合激素和代谢信号，调节脂质和葡萄糖的合成及其向外周组织的转运，因此在肥胖症和 T2DM 的发生发展中发挥着重要作用。腺苷酸 5'-单磷酸激活蛋白激酶（AMPK）是真核生物细胞和整体代谢的核心调节因子，可激活产生 ATP 的过程并减少其消耗。此外，AMPK 还调节线粒体稳态并促进自噬，两者都与 IR 的发病机制有关。因此，增加 AMPK 活性被认为是预防肥胖症和 T2DM 的一种有前途的治疗策略。本综述总结了肝 AMPK 在肥胖症和 T2DM 中的作用以及 AMPK 激活剂作为代谢紊乱治疗药物的潜力。
