Mechanism of action of necroptosis in metabolic dysfunction-associated fatty liver disease and related targeted therapies
- VernacularTitle:坏死性凋亡在代谢相关脂肪性肝病中的作用机制及相关靶向治疗
- Author:
Xiang LIU
1
;
Zhijian GONG
1
;
Yaqing LIU
1
;
Jiahao HUANG
1
;
Jingya ZHAI
1
;
Hehe CUI
1
;
Yufeng XING
2
Author Information
- Publication Type:Review
- Keywords: Necroptosis; Metabolic Dysfunction-Associated Fatty Liver Disease; Signal Transduction; Therapeutics
- From: Journal of Clinical Hepatology 2026;42(9):2191-2196
- CountryChina
- Language:Chinese
- Abstract: Metabolic dysfunction-associated fatty liver disease is a common chronic liver disease worldwide， and its incidence rate continues to rise. The traditional “two-hit” theory has gradually been replaced by the “multiple-hit” hypothesis， which emphasizes the synergistic effect of multiple pathogenic factors. Necroptosis is an inflammatory form of death with both the morphological characteristics of necrosis and the signaling mechanism of apoptosis， and the core of necroptosis lies in the receptor-interacting protein kinase 1-receptor-interacting protein kinase 3-mixed lineage kinase domain-like pseudokinase signaling axis. This pathway directly leads to the death of hepatocytes， and it triggers an inflammatory response and promotes the fibrosis process by releasing damage-associated molecular patterns； the pathway is also closely associated with the metabolic reprogramming of the liver. This review summarizes the activation mechanism of necroptosis in metabolic dysfunction-associated fatty liver disease， analyzes its effect on liver inflammation， fibrosis， and metabolism， and explores its therapeutic strategies and application prospects.
