» Articles » PMID: 36077452

Autophagy Dysregulation in Metabolic Associated Fatty Liver Disease: A New Therapeutic Target

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2022 Sep 9
PMID 36077452
Authors
Affiliations
Soon will be listed here.
Abstract

Metabolic associated fatty liver disease (MAFLD) is one of the most common causes of chronic liver disease worldwide. To date, there is no FDA-approved treatment, so there is an urgent need to determine its pathophysiology and underlying molecular mechanisms. Autophagy is a lysosomal degradation pathway that removes damaged organelles and misfolded proteins after cell injury through endoplasmic reticulum stress or starvation, which inhibits apoptosis and promotes cell survival. Recent studies have shown that autophagy plays an important role in removing lipid droplets from hepatocytes. Autophagy has also been reported to inhibit the production of pro-inflammatory cytokines and provide energy for the hepatic stellate cells activation during liver fibrosis. Thyroid hormone, irisin, melatonin, hydrogen sulfide, sulforaphane, DA-1241, vacuole membrane protein 1, nuclear factor erythroid 2-related factor 2, sodium-glucose co-transporter type-2 inhibitors, immunity-related GTPase M, and autophagy-related gene 7 have been reported to ameliorate MAFLD via autophagic induction. Lipid receptor CD36, SARS-CoV-2 Spike protein and leucine aminopeptidase 3 play a negative role in the autophagic function. This review summarizes recent advances in the role of autophagy in MAFLD. Autophagy modulates major pathological changes, including hepatic lipid metabolism, inflammation, and fibrosis, suggesting the potential of modulating autophagy for the treatment of MAFLD.

Citing Articles

Autophagy and the peroxisome proliferator-activated receptor signaling pathway: A molecular ballet in lipid metabolism and homeostasis.

Kiani P, Khodadadi E, Nikdasti A, Yarahmadi S, Gheibi M, Yousefi Z Mol Cell Biochem. 2025; .

PMID: 39891864 DOI: 10.1007/s11010-025-05207-0.


Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/SIRT1 signaling pathways.

Xu C, Wang S, Meng D, Wang M, Yan R, Dai Y BMC Gastroenterol. 2025; 25(1):47.

PMID: 39885382 PMC: 11783944. DOI: 10.1186/s12876-025-03632-5.


Tat-Beclin-1 Peptide Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by Enhancing Hepatic Autophagy.

Chen C, Huang F, Lin H, Wu C, Ni Y, Lin Y Int J Mol Sci. 2024; 25(22).

PMID: 39596437 PMC: 11594940. DOI: 10.3390/ijms252212372.


Protective Effect of Modified Suanmei-Tang on Metabolic-Associated Fatty Liver Disease: An Integrated Strategy of Network Pharmacology, Metabolomics, and Transcriptomics.

Wang C, Zhao M, Yue Y, Hu C, Zhou C, Zhang Z Drug Des Devel Ther. 2024; 18:5161-5182.

PMID: 39559790 PMC: 11572505. DOI: 10.2147/DDDT.S478072.


The pivotal role of dysregulated autophagy in the progression of non-alcoholic fatty liver disease.

Shen Q, Yang M, Wang S, Chen X, Chen S, Zhang R Front Endocrinol (Lausanne). 2024; 15:1374644.

PMID: 39175576 PMC: 11338765. DOI: 10.3389/fendo.2024.1374644.


References
1.
Ashrafizadeh M, Paskeh M, Mirzaei S, Gholami M, Zarrabi A, Hashemi F . Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response. J Exp Clin Cancer Res. 2022; 41(1):105. PMC: 8939209. DOI: 10.1186/s13046-022-02293-6. View

2.
Mazur-Bialy A, Pochec E, Zarawski M . Anti-Inflammatory Properties of Irisin, Mediator of Physical Activity, Are Connected with TLR4/MyD88 Signaling Pathway Activation. Int J Mol Sci. 2017; 18(4). PMC: 5412287. DOI: 10.3390/ijms18040701. View

3.
Eslam M, Sanyal A, George J . MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020; 158(7):1999-2014.e1. DOI: 10.1053/j.gastro.2019.11.312. View

4.
Schwimmer J, Deutsch R, Rauch J, Behling C, Newbury R, Lavine J . Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr. 2003; 143(4):500-5. DOI: 10.1067/S0022-3476(03)00325-1. View

5.
Zhou J, Tripathi M, Ho J, Widjaja A, Shekeran S, Camat M . Thyroid Hormone Decreases Hepatic Steatosis, Inflammation, and Fibrosis in a Dietary Mouse Model of Nonalcoholic Steatohepatitis. Thyroid. 2022; 32(6):725-738. DOI: 10.1089/thy.2021.0621. View