从营养过剩到肝损伤：AMP 激活的蛋白激酶在非酒精性脂肪性肝病中的作用。
From overnutrition to liver injury: AMP-activated protein kinase in nonalcoholic fatty liver diseases.
机构信息
Department of Medicine, University of California San Diego, La Jolla, California, USA.
Department of Medicine, University of California San Diego, La Jolla, California, USA; Department of Pharmacology, University of California San Diego, La Jolla, California, USA.
出版信息
J Biol Chem. 2020 Aug 21;295(34):12279-12289. doi: 10.1074/jbc.REV120.011356. Epub 2020 Jul 10.
Nonalcoholic fatty liver diseases (NAFLDs), especially nonalcoholic steatohepatitis (NASH), have become a major cause of liver transplant and liver-associated death. However, the pathogenesis of NASH is still unclear. Currently, there is no FDA-approved medication to treat this devastating disease. AMP-activated protein kinase (AMPK) senses energy status and regulates metabolic processes to maintain homeostasis. The activity of AMPK is regulated by the availability of nutrients, such as carbohydrates, lipids, and amino acids. AMPK activity is increased by nutrient deprivation and inhibited by overnutrition, inflammation, and hypersecretion of certain anabolic hormones, such as insulin, during obesity. The repression of hepatic AMPK activity permits the transition from simple steatosis to hepatocellular death; thus, activation might ameliorate multiple aspects of NASH. Here we review the pathogenesis of NAFLD and the impact of AMPK activity state on hepatic steatosis, inflammation, liver injury, and fibrosis during the transition of NAFL to NASH and liver failure.
非酒精性脂肪性肝病（NAFLD），尤其是非酒精性脂肪性肝炎（NASH），已成为肝移植和与肝相关死亡的主要原因。然而，NASH 的发病机制仍不清楚。目前，还没有 FDA 批准的药物来治疗这种毁灭性的疾病。腺苷酸活化蛋白激酶（AMPK）感知能量状态并调节代谢过程以维持体内平衡。AMPK 的活性受营养物质（如碳水化合物、脂质和氨基酸）的可用性调节。营养物质缺乏会增加 AMPK 的活性，而肥胖时营养过剩、炎症和某些合成代谢激素（如胰岛素）的过度分泌会抑制 AMPK 的活性。肝 AMPK 活性的抑制允许从单纯性脂肪变性向肝细胞死亡的转变；因此，激活可能改善 NASH 的多个方面。在这里，我们综述了 NAFLD 的发病机制以及 AMPK 活性状态对从单纯性脂肪变性向 NASH 和肝衰竭转变过程中肝脂肪变性、炎症、肝损伤和纤维化的影响。
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