ArticleFree radical biology & medicine2021
Activation of PPARα-catalase pathway reverses alcoholic liver injury via upregulating NAD synthesis and accelerating alcohol clearance.
Article in Free radical biology & medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Subchronic GenX Exposure Induces Hepatic Alterations Accompanied by Changes in PPAR-Related Lipid Metabolism and Autophagy-Related Proteins in Adult Male C57BL/6J Mice: Partial Attenuation by Chlorogenic Acid.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Peroxisomes in Liver Diseases: From Metabolite Quality Control to Inter-Organelle and Inter-Organ Signaling.Biomolecules · 2026Review
- Hepatic Hamp restoration contributes to nicotinamide mononucleotide (NMN)-alleviated hepatic steatosis in chronic alcohol-fed mice.Communications biology · 2026Article
- Microbiome-Based Clustering Identifies Glycemic Control-Related Subtypes in Youth With Recent-Onset Type 1 Diabetes.MedComm · 2026Article
- 1,2-propanediol ameliorated radiation-induced intestinal injury in mice.Scientific reports · 2026Article
- Lower L-glutamine abundance and higher HSPA8 activity contribute to the mitigation of ethanol-induced liver cell injury by thymol.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- B-Cell Receptor-Associated Protein 31 Deficiency Aggravates Ethanol-Induced Liver Steatosis and Liver Injury via Attenuating Fatty Acid Oxidation and Glycogen Synthesis.International journal of molecular sciences · 2025Article
- Phytol enhances catalase-dependent ethanol metabolism in liver independent of PPARα.Free radical biology & medicine · 2025Article
- Key Transcription Factors: Avenue for Treating Alcoholic Liver Disease.Current medical science · 2025Review
- Protective Effects of Fish Oil Against Brain Impairment in Rats with Chronic Ethanol-Induced Liver Damage Involving the NRF2 Pathway and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Research progress in the role of gut microbiota in ethanol metabolism.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Review
- NADK as a molecular marker to distinguish between alcohol- and non-alcohol-associated liver cirrhosis: A pilot study.Clinical and experimental hepatology · 2025Article
- Oral iron sulfide prevents acute alcohol intoxication by initiating the endogenous multienzymatic antioxidant defense system.Science advances · 2025Article
- Prospects of elafibranor in treating alcohol-associated liver diseases.World journal of gastroenterology · 2025Article
- Free Cholesterol-Induced Liver Injury in Non-Alcoholic Fatty Liver Disease: Mechanisms and a Therapeutic Intervention Using Dihydrotanshinone I.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oxidative stress modulation in alcohol-related liver disease: From chinese botanical drugs to exercise-based interventions.Frontiers in pharmacology · 2025Review
- Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease.World journal of gastroenterology · 2024Article
- Interaction between fatty acid oxidation and ethanol metabolism in liver.American journal of physiology. Gastrointestinal and liver physiology · 2024Review
- Regulation Mechanism and Potential Value of Active Substances in Spices in Alcohol-Liver-Intestine Axis Health.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Alcohol metabolism in the liver simultaneously generates toxic metabolites and disrupts redox balance, but the regulatory mechanisms have not been fully elucidated. The study aimed to characterize the role of PPARα in alcohol detoxification. Hepatic PPARα and catalase levels were examined in patients with severe alcoholic hepatitis. Mouse studies were conducted to determine the effect of PPARα reactivation by Wy14,643 on alcoholic hepatotoxicity and how catalase is involved in mediating such effects. Cell culture study was conducted to determine the effect of hydrogen peroxide on cellular NAD levels. We found that the protein levels of PPARα and catalase were significantly reduced in the livers of patients with severe alcoholic hepatitis. PPARα reactivation by Wy14,643 effectively reversed alcohol-induced liver damage in mice. Global and targeted metabolites analysis revealed a fundamental role of PPARα in regulating the tryptophan-NAD pathway. Notably, PPARα activation completely switched alcohol metabolism from the CYP2E1 pathway to the catalase pathway along with accelerated alcohol clearance. Catalase knockout mice were incompetent in alcohol metabolism and hydrogen peroxide clearance and were more susceptible to alcohol-induced liver injury. Hydrogen peroxide-treated hepatocytes had a reduced size of cellular NAD pool. These data demonstrate a key role of PPARα in regulating hepatic alcohol detoxification. Catalase-mediated hydrogen peroxide removal represents an underlying mechanism of how PPARα preserves the NAD pool. The study provides a new angle of view about the PPARα-catalase pathway in combating alcohol toxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.