Abstract
Autophagy is an evolutionarily conserved lysosome-mediated cellular degradation program. Accumulating evidence shows that autophagy is important to the maintenance of liver homeostasis. Autophagy involves recycling of cellular nutrients recycling as well as quality control of subcellular organelles. Autophagy deficiency in the liver causes various liver pathologies. Fatty liver disease (FLD) is characterized by the accumulation of lipids in hepatocytes and the dysfunction in energy metabolism. Autophagy is negatively affected by the pathogenesis of FLD and the activation of autophagy could ameliorate steatosis, which suggests a potential therapeutic approach to FLD. In this review, we will discuss autophagy and its relevance to liver diseases, especially FLD. In addition, we will discuss recent findings on potential therapeutic applications of autophagy modulators for FLD.
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Abbreviations
- 3-MA:
-
3-Methyl adenine
- AFLD:
-
Alcoholic fatty liver disease
- AMPK:
-
AMP-activated protein kinase
- Atg:
-
Autophagy-related proteins
- CMA:
-
Chaperone-mediated autophagy
- DAMPs:
-
Danger-associated molecular patterns
- ECM:
-
Extracellular matrix
- ER:
-
Endoplasmic reticulum
- ERQC:
-
Endoplasmic reticulum quality control
- FAs:
-
Fatty acids
- FLD:
-
Fatty liver disease
- HCC:
-
Hepatocellular carcinoma
- HSC:
-
Hepatic stellate cells
- LDs:
-
Lipid droplets
- MDB:
-
Mallory–Denk body
- mTOR:
-
Mammalian target of rapamycin
- NAC:
-
N-Acetyl cysteine
- NAFLD:
-
Non-alcoholic fatty liver disease
- PAMPs:
-
Pathogen-associated molecular patterns
- DAMPs:
-
Danger-associated molecular patterns
- PI3K:
-
Class III phosphatidylinositol 3-kinase
- PKA:
-
Ras/cAMP-dependent protein kinase A
- TFEB:
-
Transcription factor EB
- ULK1:
-
UNC-5-like autophagy-activating kinase 1
- UPR:
-
Unfolded protein response
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The authors are partially supported by NIH research Grants (R21-AA021450 and R01-AA021751).
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Yan, S., Huda, N., Khambu, B. et al. Relevance of autophagy to fatty liver diseases and potential therapeutic applications. Amino Acids 49, 1965–1979 (2017). https://doi.org/10.1007/s00726-017-2429-y
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DOI: https://doi.org/10.1007/s00726-017-2429-y