Mechanism of action of necroptosis in metabolic dysfunction-associated fatty liver disease and related targeted therapies

Xiang Liu; Zhijian Gong; Yaqing Liu; Jiahao Huang; Jingya Zhai; Hehe Cui; Yufeng Xing

doi:10.12449/JCH260925

Volume 42 Issue 9

Sep. 2026

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Article Navigation > Journal of Clinical Hepatology > 2026 > 42(9): 2191-2196

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Mechanism of action of necroptosis in metabolic dysfunction-associated fatty liver disease and related targeted therapies

DOI: 10.12449/JCH260925

1.
The Fourth Clinical Medical College，Guangzhou University of Chinese Medicine，Shenzhen，Guangdong 518000，China
2.
Department of Hepatology，Shenzhen Traditional Chinese Medicine Hospital，Shenzhen，Guangdong 518000，China

Research funding:

Shenzhen Science and Technology Plan Project (JCYJ20250604145810014);

Shenzhen Science and Technology Plan Project (JCYJ20240813152444057);

Shenzhen Medical and Health Three Famous Project (SZZYSM202411013)

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Corresponding author: Xing Yufeng， yufeng000729@163.com （ORCID： 0000-0001-6762-3788）
Received Date: 2025-12-11
Accepted Date: 2026-02-26
Published Date: 2026-09-25

Abstract

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 The traditional “two-hit” theory has gradually been replaced by the “multiple-hit” hypothesis， which emphasizes the synergistic effect of multiple pathogenic factors.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.
- Necroptosis,
- Metabolic Dysfunction-Associated Fatty Liver Disease,
- Signal Transduction,
- Therapeutics

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References(48)

References

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Mechanism of action of necroptosis in metabolic dysfunction-associated fatty liver disease and related targeted therapies

DOI: 10.12449/JCH260925

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Mechanism of action of necroptosis in metabolic dysfunction-associated fatty liver disease and related targeted therapies

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