Alcohol effects on hepatic lipid metabolism
Open accessAbstract
Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease with significant morbidity and mortality worldwide. ALD begins with simple hepatic steatosis and progresses to alcoholic steatohepatitis, fibrosis, and cirrhosis. The severity of hepatic steatosis is highly associated with the development of later stages of ALD. This review explores the disturbances of alcohol-induced hepatic lipid metabolism through altered hepatic lipid uptake, de novo lipid synthesis, fatty acid oxidation, hepatic lipid export, and lipid droplet formation and catabolism. In addition, we review emerging data on the contributions of genetics and bioactive lipid metabolism in alcohol-induced hepatic lipid accumulation.
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Alcohol-induced dysregulation of mitochondrial β-oxidation is considered the most significant contribution to lipid accumulation in the liver.
“It should be noted that alcohol-induced dysregulation of mitochondrial β-oxidation is considered the most significant contribution to lipid accumulation in the liver [46].”
From Pathophysiological Aspects of Alcohol Metabolism in the Liver (2021) · cites this paper as [46]
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“Since AMPK activation is known to regulate both β-oxidation and lipogenesis [68], this could have prevented an ethanol-mediated decrease in major antioxidant enzymes, cytosolic and mitochondrial SOD1/2, which would alleviate ROS production by ethanol metabolism and formation of acrolein adducts.”
BackgroundPark, W., Song, G., Noh, J., Kim, T., Kim, J. J., Hong, S., Park, J., & Um, J. (2021) · Nutrients · doi:10.3390/nu13124448 · Cited by 14 · see citing works
“Second, alcohol promotes the mobilization of FAs and lipids from adipose tissue and the intestine to the liver [31].”
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“ALD is a spectrum of liver diseases caused by chronic alcohol exposure (Jeon and Carr, 2020).”
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“[59] Mechanistically, alcohol promotes the accumulation of fat in the liver primarily through the substitution of ethanol instead of fatty acids for energy [60].”
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“Besides, alcohol may influence the metabolisms of many lipid classes, such as lysophosphatidylcholines (LPC), lysophosphatidylethanolamines (LPE) and ceramides [9].”
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“Furthermore, numerous studies, including ours, in both humans and complementary animal models, have demonstrated that hepatocytes drive increased fatty acid metabolism and accumulate lipids in response to heavy alcohol consumption 18,19 .”
Arumugam, M., Perumal, S. K., Rasineni, K., Donohue, T., Osna, N., & Kharbanda, K. (2023) · Biology · doi:10.3390/biology12030462 · Cited by 12
“These neutral lipids, such as CE and TAG are uncharged, have no signaling properties, and are often enclosed within LDs [13,49,50].”
BackgroundTherapeutic Pipeline in Alcohol-Associated Liver Disease
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Lipoprotein cholesterol ratios and cardiovascular disease risk in US adults: a cross-sectional study
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Impact of binge drinking on alcoholic liver disease
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“In addition to serving as a fatty acid substrate, alcohol affects various lipid regulatory factors and lipogenic enzymes, resulting in increased hepatic triglyceride levels (Jeon and Carr 2020).”
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“Glucolipid metabolism can be influenced by factors such as gender 30 , alcohol consumption 31 , cigarette consumption 32 and sleep duration 33 , etc., meanwhile, HP and DM were considered as the traditional risk factors.”
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“Excessive ceramide accumulation is known to be a key pathological feature of ALD in both human patients and animal models [11].”
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“…hepatic steatosis, the earliest response to heavy drinking, is caused by increased intrahepatic lipid biosynthesis, enhanced uptake of exogenous fatty acid from the plasma, and decreased fatty acid oxidation and secretion of very low-density lipoprotein (Jeon and Carr 2020; Yang et al.”
BackgroundDai, W., Wang, K.-Y., Zhen, X., Huang, Z.-B., & Liu, L. (2022) · Nutrition and Metabolism · doi:10.1186/s12986-022-00655-7 · Cited by 11
“Alcoholinduced liver fatty acid uptake, impairment of fatty acid oxidation, promotion of de novo lipid synthesis, neutral lipid storage and inhibition of lipid export are all pathways leading to lipid accumulation in hepatocytes [11, 12].”
BackgroundOverview of Ferroptosis in Cadmium Toxicity
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“Excessive intake of alcohol and carbohydrates can also lead to increased lipid concentrations in the blood [26,27].”
Tan, Y., Wang, Y., Wan, Y., Liang, Y., Liu, Q., Wei, M., & Hou, T. (2024) · Foods · doi:10.3390/foods13050745 · Cited by 9 · see citing works
“[ 13].”
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“When-ever the body demands energy, lipids undergo decomposition into fatty acids and glycerol, subsequently undergoing further processing to generate ATP, the primary fuel for powering physiological functions [9, 10].”
BackgroundLiang, X., Shan, T., Zheng, X., Zhang, Z., Fan, Y., Zhang, H., Zhang, L., & Liang, H. (2024) · Nutrients · doi:10.3390/nu16234170 · Cited by 7 · see citing works
“In addition, there is also evidence that alcohol can also change lipid metabolism [22].”
Alcohol-associated liver disease — a current overview
Mirowski, K., Balicka-Ślusarczyk, B., Hydzik, P., & Zwolinska-Wcislo, M. M. (2024) · Folia Medica Cracoviensia · doi:10.24425/fmc.2024.150156 · Cited by 10 · see citing works
“Ethanol induces the activation of protein SREBP-1, which promotes the transcription of lipogenic genes, increasing fatty acid synthesis [16, 18].”
BackgroundElevated systemic total bile acids escalate susceptibility to alcohol-associated liver disease
Paudel, D., Hao, F.-H., Goand, U., Tian, S.-S., Koehle, A. M., Nguyen, L. V., Tian, Y., Patterson, A., & Singh, V. (2024) · iScience · doi:10.1016/j.isci.2024.110940 · Cited by 9
“58 Chronic alcohol consumption is shown to impair the Sirt1-AMPK axis and mitochondrial b -oxidation process.”
- Authors
- Jeon, S., & Carr, R.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Carr, Rotonya
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 61
- Issue
- 4
- Pages
- 470-479
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC7112138
- OpenAlex
- W3005408539
- Cited by
- 326
- References
- 161
- Citations by year
- 2026: 58 · 2025: 78 · 2024: 76 · 2023: 49 · 2022: 45 · 2021: 13 · 2020: 7
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R01 AA026302-02, P30 DK0503060)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- alcoholic liver disease, hepatic lipid metabolism, hepatic steatosis, alcoholic steatohepatitis, fatty acid oxidation, de novo lipogenesis, lipid export, lipid droplet formation, genetic susceptibility, bioactive lipids, liver fibrosis
- MeSH terms
- Ethanol, Animals, Humans, Liver, Lipogenesis, Lipid Metabolism
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