Mechanism of action of lipid metabolic reprogramming in the progression of metabolic dysfunction-associated fatty liver disease
- VernacularTitle:脂质代谢重编程在代谢相关脂肪性肝病进展中的作用机制
- Author:
Xinyue CHENG
1
;
Lei LUO
2
;
Rong LIU
1
;
Shuaibing CAO
1
;
Baoping LU
1
Author Information
- Publication Type:Review
- Keywords: Lipid Metabolic Reprogramming; Metabolic Dysfunction-Associated Fatty Liver Disease; Metabolic Dysfunction-Associated Steatohepatitis; Fatty Acids
- From: Journal of Clinical Hepatology 2026;42(9):2176-2182
- CountryChina
- Language:Chinese
- Abstract: Metabolic dysfunction-associated fatty liver disease （MAFLD） is the chronic liver disease with the highest prevalence rate globally， and its disease spectrum encompasses a progressive continuum from hepatic steatosis to metabolic dysfunction-associated steatohepatitis， liver fibrosis， liver cirrhosis， and eventually hepatocellular carcinoma. In recent years， the research paradigm of MAFLD has shifted from “lipid accumulation” to “lipid metabolic reprogramming”， which， as a critical link in disease development and progression， is regulated by multidimensional molecular networks. This article systematically reviews the molecular mechanisms of lipid metabolic reprogramming in MAFLD from the following aspects： it analyzes the core role of lipid metabolism disorders， with a focus on how dysregulation of membranous organelle interactions， such as endoplasmic reticulum-mitochondria contacts， mediates metabolic imbalance； it concentrates on novel programmed cell death pathways induced by lipotoxicity， especially ferroptosis， and reveals the pathways through which they exacerbate liver injury； furthermore， it comprehensively analyzes the multi-layered regulatory network of the key signaling pathways such as adenosine monophosphate-activated protein kinase and nuclear factor-erythroid 2-related factor 2 and explores the emerging mechanisms such as liquid-liquid phase separation and microprotein regulation； finally， it provides an outlook on the potential therapeutic strategies targeting critical nodes of lipid metabolic reprogramming， so as to provide a theoretical basis for investigating the pathological mechanisms of MAFLD and developing precise interventions.
