Role of Alcohol Metabolism in Non-Alcoholic Steatohepatitis 英文参考文献.docVIP

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Role of Alcohol Metabolism in Non-Alcoholic Steatohepatitis 英文参考文献.doc

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Role of Alcohol Metabolism in Non-Alcoholic Steatohepatitis 英文参考文献

RoleofAlcoholMetabolisminNon-Alcoholic Steatohepatitis SusanS.Baker1,RobertD.Baker1,WenshengLiu1,NormaJ.Nowak2,3,LixinZhu1* 1Digestive Diseases and Nutrition Center, Department of Pediatrics, TheState University of New York, Buffalo, New York, United States of America, 2Department of BiochemistryandtheNewYorkStateCenterofExcellenceinBioinformaticsandLifeSciences,TheStateUniversityofNewYorkatBuffalo,Buffalo,NewYork,UnitedStates ofAmerica,3MicroarrayandGenomicsFacility,RoswellParkCancerInstitute,Buffalo,NewYork,UnitedStatesofAmerica Abstract Background:Non-alcoholicsteatohepatitis(NASH)isaseriousformofnon-alcoholicfattyliverdisease(NAFLD),associated withobesityandinsulinresistance.Previousstudiessuggestedthatintestinalbacteriaproducedmorealcoholinobesemice thanleananimals. Methodology/PrincipalFindings:ToinvestigatewhetheralcoholisinvolvedinthepathogenesisofNASH,theexpression ofinflammation,fibrosisandalcoholmetabolismrelatedgenesinthelivertissuesofNASHpatientsandnormalcontrols (NCs)wereexaminedbymicroarray(NASH,n=7;NC,n=4)andquantitativereal-timePCR(NASH,n=6;NC,n=6).Genes relatedtoliverinflammationandfibrosiswerefoundtobeelevatedinNASHliverscomparedtonormallivers.Themost striking finding is the increased gene transcription of alcohol dehydrogenase (ADH) genes, genes for catalase and cytochrome P450 2E1, and aldehyde dehydrogenase genes. Immunoblot analysis confirmed the increased expression of ADH1andADH4inNASHlivers(NASH,n=9;NC,n=4). Conclusions/Significance:Theaugmentedactivityofalltheavailablegenesofthepathwaysforalcoholcatabolismsuggest that1)alcoholconcentrationwaselevatedinthecirculationofNASHpatients;2)therewasahighpriorityfortheNASH liverstoscavengealcoholfromthecirculation.Ourdataisthefirsthumanevidencethatsuggestsalcoholmaycontributeto thedevelopmentofNAFLD. Citation:BakerSS,BakerRD,LiuW,NowakNJ,ZhuL(2010)RoleofAlcoholMetabolisminNon-AlcoholicSteatohepatitis.PLoSONE5(3):e9570.doi:10.1371/ journal.pone.0009570 Editor:ChristianGluud,CopenhagenUniversityHosp