Cited by 312Alcohol Consumption and Health EffectsLiver Disease Diagnosis and TreatmentLiver physiology and pathology

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Molecular Mechanisms of Alcoholic Fatty Liver

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Purohit, Vishnudutt, Gao, Bin, Song, Byoung‐Joon·2009·Alcoholism: Clinical and Experimental Research

DOI 10.1111/j.1530-0277.2008.00827.xPMC PMC2633431

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Abstract

Alcoholic fatty liver is a potentially pathologic condition which can progress to steatohepatitis, fibrosis, and cirrhosis if alcohol consumption is continued. Alcohol exposure may induce fatty liver by increasing NADH/NAD+ratio, increasing sterol regulatory element‐binding protein‐1 (SREBP‐1) activity, decreasing peroxisome proliferator‐activated receptor‐α (PPAR‐α) activity, and increasing complement C3 hepatic levels. Alcohol may increase SREBP‐1 activity by decreasing the activities of AMP‐activated protein kinase and sirtuin‐1. Tumor necrosis factor‐α (TNF‐α) produced in response to alcohol exposure may cause fatty liver by up‐regulating SREBP‐1 activity, whereas betaine and pioglitazone may attenuate fatty liver by down‐regulating SREBP‐1 activity. PPAR‐α agonists have potentials to attenuate alcoholic fatty liver. Adiponectin and interleukin‐6 may attenuate alcoholic fatty liver by up‐regulating PPAR‐α and insulin signaling pathways while down‐regulating SREBP‐1 activity and suppressing TNF‐α production. Recent studies show that paracrine activation of hepatic cannabinoid receptor 1 by hepatic stellate cell‐derived endocannabinoids also contributes to the development of alcoholic fatty liver. Furthermore, oxidative modifications and inactivation of the enzymes involved in the mitochondrial and/or peroxisomal β‐oxidation of fatty acids could contribute to fat accumulation in the liver.

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10.1172/JCI200523057 · DOI

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Alcoholic liver disease
Seitz, H. K., Bataller, R., Cortez-Pinto, H., Gao, B., Gual, A., Lackner, C., Mathurin, P., Mueller, S., Szabo, G., & Tsukamoto, H. (2018) · Nature Reviews Disease Primers · doi:10.1038/s41572-018-0014-7 · Cited by 1,271
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Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury
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Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction
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CYP2E1 potentiates binge alcohol-induced gut leakiness, steatohepatitis, and apoptosis
Abdelmegeed, M. A., Banerjee, A., Jang, S., Yoo, S.-H., Yun, J.-W., Gonzalez, F. J., Keshavarzian, A., & Song, B.-J. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.09.009 · Cited by 191
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Mitochondrial dysfunction and tissue injury by alcohol, high fat, nonalcoholic substances and pathological conditions through post-translational protein modifications
Song, B.-J., Akbar, M., Abdelmegeed, M. A., Byun, K., Lee, B., Yoon, S. K., & Hardwick, J. P. (2014) · Redox Biology · doi:10.1016/j.redox.2014.10.004 · Cited by 123
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Authors: Purohit, V., Gao, B., & Song, B.
Affiliations: National Institutes of Health (US)
Corresponding author: Purohit, Vishnudutt
ORCID: Gao, Bin
Song, Byoung‐Joon
Venue: Alcoholism: Clinical and Experimental Research
Publisher: Wiley
Published: 2009-01-22
Volume: 33
Issue: 2
Pages: 191-205
ISSN: 0145-6008 (ISSN-L)
1530-0277
DOI: 10.1111/j.1530-0277.2008.00827.x
PMC: PMC2633431
OpenAlex: W2066238144
Cited by: 312
References: 214
Citations by year: 2026: 5 · 2025: 9 · 2024: 18 · 2023: 18 · 2022: 12 · 2021: 16 · 2020: 17 · 2019: 20 · 2018: 14 · 2017: 20 · 2016: 17 · 2015: 24 · 2014: 26 · 2013: 16 · 2012: 28
FWCI: 2.03
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Alcoholism Clinical and Experimental Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (Z99‐AA999999, Z99 DA999999)
National Institute on Alcohol Abuse and Alcoholism (Z01AA000036)
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords: alcoholic fatty liver, steatohepatitis, liver fibrosis, liver cirrhosis, SREBP1, PPARα, NAD+/NADH ratio, AMPK, SIRT1, TNF-α, complement C3, betaine, pioglitazone, adiponectin, interleukin-6, insulin signaling, hepatic stellate cells, CB1 receptor, endocannabinoids, fatty acid beta-oxidation, oxidative modification, hepatic lipid accumulation
MeSH terms: Animals, Complement C3, Fatty Liver, Alcoholic, Humans, NAD, Tumor Necrosis Factor-alpha, PPAR alpha, Sterol Regulatory Element Binding Proteins

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Molecular Mechanisms of Alcoholic Fatty Liver

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