PMID- 37629519
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230829
IS  - 2075-1729 (Print)
IS  - 2075-1729 (Electronic)
IS  - 2075-1729 (Linking)
VI  - 13
IP  - 8
DP  - 2023 Jul 30
TI  - Pathogenesis of Alcoholic Fatty Liver a Narrative Review.
LID - 10.3390/life13081662 [doi]
LID - 1662
AB  - Alcohol effect hepatic lipid metabolism through various mechanisms, leading 
      synergistically to an accumulation of fatty acids (FA) and triglycerides. 
      Obesity, as well as dietary fat (saturated fatty acids (FA) versus 
      poly-unsaturated fatty acids (PUFA)) may modulate the hepatic fat. Alcohol 
      inhibits adenosine monophosphate activated kinase (AMPK). AMPK activates 
      peroxisome proliferator activated receptor a (PPARalpha) and leads to a decreased 
      activation of sterol regulatory element binding protein 1c (SRABP1c). The 
      inhibition of AMPK, and thus of PPARalpha, results in an inhibition of FA oxidation. 
      This ss-oxidation is further reduced due to mitochondrial damage induced through 
      cytochrome P4502E1 (CYP2E1)-driven oxidative stress. Furthermore, the synthesis 
      of FAs is stimulated through an activation of SHREP1. In addition, alcohol 
      consumption leads to a reduced production of adiponectin in adipocytes due to 
      oxidative stress and to an increased mobilization of FAs from adipose tissue and 
      from the gut as chylomicrons. On the other side, the secretion of FAs via 
      very-low-density lipoproteins (VLDL) from the liver is inhibited by alcohol. 
      Alcohol also affects signal pathways such as early growth response 1 (Egr-1) 
      associated with the expression of tumour necrosis factor alpha (TNF alpha), and the 
      mammalian target of rapamycin (mTOR) a key regulator of autophagy. Both have 
      influence the pathogenesis of alcoholic fatty liver. Alcohol-induced gut 
      dysbiosis contributes to the severity of ALD by increasing the metabolism of 
      ethanol in the gut and promoting intestinal dysfunction. Moreover, 
      pathogen-associated molecular patterns (PAMPS) via specific Toll-like receptor 
      (TLR) bacterial overgrowth leads to the translocation of bacteria. Endotoxins and 
      toxic ethanol metabolites enter the enterohepatic circulation, reaching the liver 
      and inducing the activation of the nuclear factor kappa-B (NFkappaB) pathway. 
      Pro-inflammatory cytokines released in the process contribute to inflammation and 
      fibrosis. In addition, cellular apoptosis is inhibited in favour of necrosis.
FAU - Seitz, Helmut K
AU  - Seitz HK
AD  - Centre of Liver and Alcohol Associated Diseases, Ethianum Clinic, Faculty of 
      Medicine, University of Heidelberg, 69120 Heidelberg, Germany.
FAU - Moreira, Bernardo
AU  - Moreira B
AD  - Centre of Liver and Alcohol Associated Diseases, Ethianum Clinic, Faculty of 
      Medicine, University of Heidelberg, 69120 Heidelberg, Germany.
FAU - Neuman, Manuela G
AU  - Neuman MG
AD  - In Vitro Drug Safety and Biotechnology, Department of Pharmacology and 
      Toxicology, Temerity Faculty of Medicine, University of Toronto, Banting 
      Institute, Toronto, ON M5G 1L5, Canada.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230730
PL  - Switzerland
TA  - Life (Basel)
JT  - Life (Basel, Switzerland)
JID - 101580444
PMC - PMC10455719
OTO - NOTNLM
OT  - adenosine monophosphate activated kinase
OT  - alcoholic fatty liver
OT  - cytochrome P450 2E1
OT  - oxidative stress
OT  - peroxisome proliferator activated receptor alpha
OT  - sterol regulatory element binding protein 1c
COIS- The authors declare no conflict of interest.
EDAT- 2023/08/26 10:42
MHDA- 2023/08/26 10:43
PMCR- 2023/07/30
CRDT- 2023/08/26 01:19
PHST- 2023/05/08 00:00 [received]
PHST- 2023/07/12 00:00 [revised]
PHST- 2023/07/28 00:00 [accepted]
PHST- 2023/08/26 10:43 [medline]
PHST- 2023/08/26 10:42 [pubmed]
PHST- 2023/08/26 01:19 [entrez]
PHST- 2023/07/30 00:00 [pmc-release]
AID - life13081662 [pii]
AID - life-13-01662 [pii]
AID - 10.3390/life13081662 [doi]
PST - epublish
SO  - Life (Basel). 2023 Jul 30;13(8):1662. doi: 10.3390/life13081662.