Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1α in rats
Abstract
The nuclear genes, NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-gamma coactivator1alpha (PGC-1alpha) are regulators of energy metabolism. Here, we studied the role of alcohol consumption in expression of these sensing molecules. Alcohol significantly reduced hepatic SIRT1 mRNA by 50% and PGC-1alpha mRNA by 46% and it significantly inhibited the protein expression of SIRT1 and PGC-1alpha, while the transcription factor PPAR-gamma remained unchanged. However, when the lipid composition of the alcohol diet was changed by replacing long-chain triglycerides (LCT) with medium chain triglycerides (MCT), SIRT1 and PGC-1alpha mRNA were restored to near control levels. This study demonstrates that alcohol reduces key energy sensing proteins and that replacement of LCT by MCT affects the transcription of these genes. Since there is a pathophysiological link between SIRT1 and PGC-1alpha and mitochondrial energy, the implication of the study is that mitochondrial dysfunction due to alcohol abuse can be treated by dietary modifications.
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Subchronic alcohol intake decreases the levels of SIRT1 and PGC-1α and other isoforms.
“Subchronic alcohol intake also decreased the levels of SIRT1 and PGC-1α and other isoforms286,287.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [286]
Chronic alcohol exposure suppressed the activities and protein amounts of sirtuin 1, 3 and 5 isoforms, in a CYP2E1-independent manner.
“Earlier reports also showed that chronic alcohol exposure suppressed the activities and protein amounts of sirtuin 1, 3 and 5 isoforms [142], [143], [144], [145], [149], [150], in a CYP2E1-independent manner [144].”
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Self-citation
- Authors
- Lieber, C. S., Leo, M. A., Wang, X., & DeCarli, L. M.
- Affiliations
- James J. Peters VA Medical Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Lieber, Charles S.
- ORCID
- Wang, Xiaolei
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 370
- Issue
- 1
- Pages
- 44-48
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2057418662
- Cited by
- 135
- References
- 28
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 13 · 2015: 13 · 2014: 9 · 2013: 5 · 2012: 10
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- chronic alcohol consumption, SIRT1, PGC-1α, PPARγ, hepatic gene expression, medium-chain triglycerides, long-chain triglycerides, dietary fat composition, mitochondrial dysfunction, energy metabolism, alcohol-induced liver damage
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Alcohol Drinking, Ethanol, Animals, Diet, Energy Metabolism, Liver, Male, RNA, Messenger, Transcription Factors, Transcription, Genetic, Triglycerides, Down-Regulation, RNA-Binding Proteins, Rats, Sprague-Dawley, Sirtuins, PPAR gamma, Rats, Sirtuin 1
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