ArticleAlcoholism, clinical and experimental research2016
Hepatic Peroxisome Proliferator-Activated Receptor Gamma Signaling Contributes to Alcohol-Induced Hepatic Steatosis and Inflammation in Mice.
Article in Alcoholism, clinical and experimental research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 75 citations in OpenAlex.
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- The Mediator Complex: A Regulatory Hub for Transcriptional Activity of Nuclear Receptors.Cells · 2025Review
- Circulating Extracellular Vesicles in Alcoholic Liver Disease Affect Skeletal Muscle Homeostasis and Differentiation.Journal of cachexia, sarcopenia and muscle · 2025Article
- Therapeutic Targeting of PPARγ in Nonalcoholic Fatty Liver Disease: Efficacy, Safety, and Drug Development.Drug design, development and therapy · 2025Review
- ASPP2 deficiency attenuates lipid accumulation through the PPARγ pathway in alcoholic liver injury.Cell biology and toxicology · 2024Article
- MiRNAs in Alcohol-Related Liver Diseases and Hepatocellular Carcinoma: A Step toward New Therapeutic Approaches?Cancers · 2023Review
- 24-Norursodeoxycholic acid ameliorates experimental alcohol-related liver disease and activates hepatic PPARγ.JHEP reports : innovation in hepatology · 2023Article
- Synergistic Protective Effect of Fermented Schizandrae Fructus Pomace and Hoveniae Semen cum Fructus Extracts Mixture in the Ethanol-Induced Hepatotoxicity.Antioxidants (Basel, Switzerland) · 2023Article
- Class III Alcohol Dehydrogenase Plays a Key Role in the Onset of Alcohol-Related/-Associated Liver Disease as an S-Nitrosoglutathione Reductase in Mice.International journal of molecular sciences · 2023Article
- Nicotinamide N-methyltransferase upregulation contributes to palmitate-elicited peroxisome proliferator-activated receptor transactivation in hepatocytes.American journal of physiology. Cell physiology · 2023Article
- Role of hepatic peroxisome proliferator-activated receptor γ in non-alcoholic fatty liver disease.The Journal of endocrinology · 2023Review
- Long noncoding RNA ACART knockdown decreases 3T3-L1 preadipocyte proliferation and differentiation.Open life sciences · 2023Article
- The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity.International journal of molecular sciences · 2022Review
- Absolute quantitative lipidomics reveals lipids profiling in liver of mice with early-stage alcoholic liver disease.Nutrition & metabolism · 2022Article
- Withaferin A alleviates ethanol-induced liver injury by inhibiting hepatic lipogenesis.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Article
- D-Mannose Regulates Hepatocyte Lipid MetabolismFrontiers in immunology · 2022Article
- Pathogenesis of Alcohol-Associated Fatty Liver: Lessons From Transgenic Mice.Frontiers in physiology · 2022Review
- Multiple Roles of SIRT2 in Regulating Physiological and Pathological Signal Transduction.Genetics research · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPeroxisome proliferator-activated receptor gamma (PPARγ) signaling has been shown to regulate lipogenesis and lipid accumulation. Previous studies have shown that hepatic PPARγ is up-regulated in steatotic liver of both animal and human. However, the effects of hepatic PPARγ signaling on alcoholic liver disease (ALD) remain elusive.
methodsTo determine the role of hepatic PPARγ signaling on ALD, wild-type (WT) and hepatocyte-specific PPARγ knockdown (PPARγ∆Hep) mice were fed a modified Lieber-DeCarli alcohol or isocaloric maltose dextrin control liquid diet for 8 weeks to induce ALD. Blood parameters, hepatic steatosis, and inflammation were measured after 8-week alcohol feeding.
resultsAlcohol feeding to WT mice resulted in liver damage (alanine aminotransferase [ALT], 94.68 ± 17.05 U/L; aspartate aminotransferase [AST], 55.87 ± 11.29 U/L), which was significantly alleviated by hepatic PPARγ knockdown (ALT, 57.36 ± 14.98 U/L; AST, 38.06 ± 3.35 U/L). Alcohol feeding led to marked lipid accumulation and up-regulation of lipogenic genes including fatty acid transport protein 1 (FATP1), acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), lipin1 (LIPIN1), diacylglycerol acyltransferase 1 (DGAT1), and diacylglycerol acyltransferase 2 (DGAT2) in the livers of WT mice. Knockdown of hepatic PPARγ significantly alleviated alcohol-induced lipid accumulation and abolished the up-regulation of FASN, DGAT1, and DGAT2. Silencing of PPARγ in FL83B cells significantly decreased ethanol (EtOH)-, linoleic acid-, and EtOH plus linoleic acid-induced lipid accumulation. Knockdown of hepatic PPARγ also significantly reduced alcohol-induced inflammatory chemokine (monocyte chemotactic protein 1 [MCP1], keratinocyte-derived chemokine [KC], interferon gamma-induced protein 10 [IP-10]) and inflammatory infiltration (lymphocyte antigen 6 complex, locus G [Ly6G], and F4/80).
conclusionsThe results suggest that hepatic PPARγ signaling contributes to alcohol-induced liver injury by promoting hepatic steatosis and inflammation.
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