ArticleAlcoholism, clinical and experimental research2015
Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans.
Article in Alcoholism, clinical and experimental research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 93 citations in OpenAlex.
- Pioglitazone for the treatment of alcohol use disorder: A randomized controlled trial.Addiction (Abingdon, England) · 2026Trial
- Assessment of pioglitazone and proinflammatory cytokines during buprenorphine taper in patients with opioid use disorder.Psychopharmacology · 2018Trial
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- Pharmacologic management of metabolic and alcohol-associated liver disease.Metabolism and target organ damage · 2026Article
- Timing matters: circadian rhythm disruption in alcohol-associated peripheral organ pathophysiology.Function (Oxford, England) · 2026Review
- Fenofibrate restores glutamatergic and dopaminergic homeostasis in the nucleus accumbens and reduces alcohol relapse in rats.Frontiers in pharmacology · 2026Article
- GLS1-RNA Polymerase II Axis Mediates Glutamine-Dependent Hepatoprotective Effects on Alcoholic Liver Disease in High-Protein Diets.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Inflammation in MASLD progression and cancer.JHEP reports : innovation in hepatology · 2025Review
- Saroglitazar Versus Simvastatin for Metabolic and Alcohol-Associated Liver Disease (MetALD).Cureus · 2025Article
- Current View on PPAR-α and Its Relation to Neurosteroids in Alzheimer's Disease and Other Neuropsychiatric Disorders: Promising Targets in a Therapeutic Strategy.International journal of molecular sciences · 2024Review
- Novel medications for problematic alcohol use.The Journal of clinical investigation · 2024Review
- Neuroimmune modulators as novel pharmacotherapies for substance use disorders.Brain, behavior, & immunity - health · 2024Article
- A reverse translational study of PPAR-α agonist efficacy in human and rodent models relevant to alcohol use disorder.Neurobiology of stress · 2024Article
- Adolescent alcohol drinking interaction with the gut microbiome: implications for adult alcohol use disorder.Advances in drug and alcohol research · 2024Article
- Fenofibrate Decreases Ethanol-Induced Neuroinflammation and Oxidative Stress and Reduces Alcohol Relapse in Rats by a PPAR-α-Dependent Mechanism.Antioxidants (Basel, Switzerland) · 2023Article
- System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.International journal of molecular sciences · 2023Article
- Review
- Effects of chronic and binge ethanol administration on mouse cerebellar and hippocampal neuroinflammation.The American journal of drug and alcohol abuse · 2023Article
- The Strategy of Targeting Peroxisome Proliferator-Activated Receptor (PPAR) in the Treatment of Neuropsychiatric Disorders.Advances in experimental medicine and biology · 2023Article
- Mechanisms underlying microRNA-222-3p modulation of methamphetamine-induced conditioned place preference in the nucleus accumbens in mice.Psychopharmacology · 2022Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundPeroxisome proliferator-activated receptor (PPAR) agonists reduce voluntary ethanol (EtOH) consumption in rat models and are promising therapeutics in the treatment for drug addictions. We studied the effects of different classes of PPAR agonists on chronic EtOH intake and preference in mice with a genetic predisposition for high alcohol consumption and then examined human genomewide association data for polymorphisms in PPAR genes in alcohol-dependent subjects.
methodsTwo different behavioral tests were used to measure intake of 15% EtOH in C57BL/6J male mice: 24-hour 2-bottle choice and limited access (3-hour) 2-bottle choice, drinking in the dark. We measured the effects of pioglitazone (10 and 30 mg/kg), fenofibrate (50 and 150 mg/kg), GW0742 (10 mg/kg), tesaglitazar (1.5 mg/kg), and bezafibrate (25 and 75 mg/kg) on EtOH intake and preference. Fenofibric acid, the active metabolite of fenofibrate, was quantified in mouse plasma, liver, and brain by liquid chromatography tandem mass spectrometry. Data from a human genome-wide association study (GWAS) completed in the Collaborative Study on the Genetics of Alcoholism (COGA) were then used to analyze the association of single nucleotide polymorphisms (SNPs) in different PPAR genes (PPARA, PPARD, PPARG, and PPARGC1A) with 2 phenotypes: DSM-IV alcohol dependence (AD) and the DSM-IV criterion of withdrawal.
resultsActivation of 2 isoforms of PPARs, α and γ, reduced EtOH intake and preference in the 2 different consumption tests in mice. However, a selective PPARδ agonist or a pan agonist for all 3 PPAR isoforms did not decrease EtOH consumption. Fenofibric acid, the active metabolite of the PPARα agonist fenofibrate, was detected in liver, plasma, and brain after 1 or 8 days of oral treatment. The GWAS from COGA supported an association of SNPs in PPARA and PPARG with alcohol withdrawal and PPARGC1A with AD but found no association for PPARD with either phenotype.
conclusionsWe provide convergent evidence using both mouse and human data for specific PPARs in alcohol action. Reduced EtOH intake in mice and the genetic association between AD or withdrawal in humans highlight the potential for repurposing FDA-approved PPARα or PPARγ agonists for the treatment of AD.
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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.