Autophagy, Ferroptosis, Apoptosis and Pyroptosis in Metabolic Dysfunction-Associated Steatotic Liver Disease

² State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022 Changchun, Jilin, China

^*Correspondence: ccguoyan@163.com (Yan Guo); xzyin@ciac.ac.cn (Xunzhe Yin)

Front. Biosci. (Landmark Ed) 2024, 29(1), 30; https://doi.org/10.31083/j.fbl2901030

Submitted: 28 October 2023 | Revised: 13 December 2023 | Accepted: 18 December 2023 | Published: 19 January 2024

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Metabolic Liver Disease-associated Hepatocellular Carcinoma)

This is an open access article under the CC BY 4.0 license.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) has a global prevalence of 25% and is a leading cause of cirrhosis and hepatocellular carcinoma. The prevalence of MASLD has been increasing, mirroring the global increase in diabetes and metabolic syndrome. MASLD is a chronic and progressive condition characterized by inflammation, oxidative stress, insulin resistance, and disruptions in lipid metabolism. Programmed cell death (PCD) plays a pivotal role in determining the pathological aspects of MASLD, including liver inflammation, fibrosis, and even the potential for malignant transformation. PCD is a dominant process that is fundamental for eukaryotic growth and serves as a regulatory factor in MASLD. PCD encompasses various pathways, including autophagy, ferroptosis, apoptosis, and pyroptosis. These PCD pathways can be activated at different stages of MASLD. The key effector molecules involved in these processes are central focal points in the development of therapeutic interventions for MASLD. Here, we comprehensively review the idea that targeted the modulation of the PCD pathway may be an effective approach for the prevention and/or treatment of MASLD.

Keywords

autophagy

ferroptosis

apoptosis

pyroptosis

metabolic dysfunction-associated steatotic liver disease

Funding

20210204029YY/Science and Technology Development Plan of Jilin Province

YDZJ202201ZYTS151/Science and Technology Development Plan of Jilin Province

Figures

Fig. 1.

Previous article in this issue

Next article in this issue

Fig. 1.

Autophagy and MASLD. The AMPK pathway is considered a key factor in slowing the progression of MASLD. When excessive fat accumulates in the liver, AMPK is inhibited. This promotes hepatic fatty acid synthesis, while concurrently suppressing fatty acid oxidation and hence reducing fatty acid consumption. This increases intracellular lipid accumulation and favors the onset and progression of MASLD. AMPK also regulates autophagy through its effects on the clearance of cellular waste and the maintenance of energy balance. AMPK activation can directly phosphorylate ULK1 to initiate autophagy. AMPK can also indirectly promote autophagy by inhibiting mTOR. Thus, AMPK-meditated autophagy facilitates the degradation of cellular waste, such as fatty acids. Abbreviations: MASLD, metabolic dysfunction-associated steatotic liver disease; HFD, high-fat diet; AMPK, AMP-activated protein kinase; ULK1, unc-51-like kinase 1; mTOR, mammalian target of rapamycin; LC3, microtubule-associated proteins 1A/1B light chain 3; FFA, free fatty acids; SREBP-1c, sterol regulatory element binding protein 1c; FAS, fatty acid synthase; PPAR $\alpha{}$ , peroxisome proliferation-activated receptor $\alpha{}$ ; CPT1, carnitine palmitoyltransferase 1. Created with BioRender.com.

1 of 5

Front. Biosci. (Landmark Ed) Print ISSN 2768-6701 Electronic ISSN 2768-6698