代谢功能障碍相关的脂肪肝病（MASLD），以前称为非酒精性脂肪肝病（NAFLD），涵盖一系列进行性肝脏疾病，从脂肪变性到代谢功能障碍相关的脂肪性肝炎，其特征是肝细胞死亡和炎症，可能进展为肝硬化和/或肝癌。在实验和人类 MASLD 中，都会触发坏死性凋亡（一种受调节的免疫原性坏死细胞死亡途径），但其在疾病发病机制中的确切作用仍不清楚。值得注意的是，坏死性凋亡相关信号通路正在成为代谢重编程（包括脂质和线粒体代谢）的关键参与者。此外，代谢失调是 MASLD 发生和进展的一个公认的因素。本综述探讨了细胞代谢和坏死性凋亡调节之间复杂的相互作用及其对 MASLD 发病机制的影响。了解这些细胞事件可能会为 MASLD 病理生理学的复杂性提供新的见解，有可能揭示针对坏死性凋亡的治疗机会和不可预见的代谢后果。版权所有 © 2024。由 Elsevier Inc. 出版。

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), encompasses a progressive spectrum of liver conditions, ranging from steatosis to metabolic dysfunction-associated steatohepatitis, characterised by hepatocellular death and inflammation, potentially progressing to cirrhosis and/or liver cancer. In both experimental and human MASLD, necroptosis-a regulated immunogenic necrotic cell death pathway-is triggered, yet its exact role in disease pathogenesis remains unclear. Noteworthy, necroptosis-related signalling pathways are emerging as key players in metabolic reprogramming, including lipid and mitochondrial metabolism. Additionally, metabolic dysregulation is a well-established contributor to MASLD development and progression. This review explores the intricate interplay between cell metabolism and necroptosis regulation and its impact on MASLD pathogenesis. Understanding these cellular events may offer new insights into the complexity of MASLD pathophysiology, potentially uncovering therapeutic opportunities and unforeseen metabolic consequences of targeting necroptosis.Copyright © 2024. Published by Elsevier Inc.