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dc.contributor.authorBlednov, Yuri A
dc.contributor.authorBenavidez, Jillian M
dc.contributor.authorBlack, Mendy
dc.contributor.authorFerguson, Laura B
dc.contributor.authorSchoenhard, Grant L
dc.contributor.authorGoate, Alison M
dc.contributor.authorEdenberg, Howard J
dc.contributor.authorWetherill, Leah
dc.contributor.authorHesselbrock, Victor
dc.contributor.authorForoud, Tatiana
dc.contributor.authorHarris, R Adron
dc.date.accessioned2023-01-23T20:01:56Z
dc.date.available2023-01-23T20:01:56Z
dc.date.issued2014-12-16
dc.identifier.citationBlednov YA, Benavidez JM, Black M, Ferguson LB, Schoenhard GL, Goate AM, Edenberg HJ, Wetherill L, Hesselbrock V, Foroud T, Harris RA. Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans. Alcohol Clin Exp Res. 2015 Jan;39(1):136-45. doi: 10.1111/acer.12610. Epub 2014 Dec 16. PMID: 25516156; PMCID: PMC4308472.en_US
dc.identifier.eissn1530-0277
dc.identifier.doi10.1111/acer.12610
dc.identifier.pmid25516156
dc.identifier.urihttp://hdl.handle.net/20.500.12648/8137
dc.description.abstractPeroxisome 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.
dc.description.abstractTwo 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.
dc.description.abstractActivation 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.
dc.description.abstractWe 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.
dc.language.isoenen_US
dc.relation.urlhttps://onlinelibrary.wiley.com/doi/10.1111/acer.12610en_US
dc.rightsCopyright © 2014 by the Research Society on Alcoholism.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectC57BL/6Jen_US
dc.subjectFenofibrateen_US
dc.subjectFenofibric Aciden_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectPioglitazoneen_US
dc.subjectTesag-litazaren_US
dc.subjectTwo-Bottle Choiceen_US
dc.titlePeroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans.en_US
dc.typeArticle/Reviewen_US
dc.source.journaltitleAlcoholism, clinical and experimental researchen_US
dc.source.volume39
dc.source.issue1
dc.source.beginpage136
dc.source.endpage45
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland
dc.description.versionAMen_US
refterms.dateFOA2023-01-23T20:01:56Z
html.description.abstractPeroxisome 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.
html.description.abstractTwo 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.
html.description.abstractActivation 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.
html.description.abstractWe 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.
dc.description.institutionSUNY Downstateen_US
dc.description.departmentHenri Begleiter Neurodynamics Laboratoryen_US
dc.description.degreelevelN/Aen_US
dc.identifier.journalAlcoholism, clinical and experimental research


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Copyright © 2014 by the Research Society on Alcoholism.
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