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Adipose基因转录调控及功能研究.docx

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Adipose基因转录调控及功能研究 Introduction Adiposetissueisanessentialcomponentofthehumanbody,whichservesmultiplefunctions,includingthestorageofexcessenergyintheformoftriglycerides,thesecretionofhormonesandcytokines,andtheregulationofmetabolism.Thedevelopmentandmaintenanceofadiposetissuearetightlyregulatedbyvariousgenesandsignalingpathways.Inthisreview,wewillfocusonthetranscriptionalregulationandfunctionsoftheAdipose(Adi)gene,whichencodesanuclearproteinthatbelongstothetranscriptionfactorfamily. TranscriptionalregulationofAdiposegene TheAdiposegeneisexpressedinavarietyoftissues,includingadiposetissue,liver,muscle,andbrain.TheexpressionofAdiposeisregulatedbyseveraltranscriptionfactors,suchasperoxisomeproliferator-activatedreceptorgamma(PPARγ),CCAAT/enhancer-bindingproteinalpha(C/EBPα),andsterolregulatoryelement-bindingprotein1c(SREBP-1c).Amongthesefactors,PPARγisthemostimportantregulatorofadipogenesisandisessentialforthedifferentiationofpreadipocytesintomatureadipocytes.PPARγbindstotheAdiposepromoterandactivatesitstranscription,therebypromotingadipocytedifferentiationandlipidaccumulation. InadditiontoPPARγ,C/EBPαalsoplaysacriticalroleinadipogenesisbyactivatingtheexpressionofPPARγandotheradipogenicgenes.C/EBPαbindstotheAdiposepromoterandenhancesitsactivity,therebycontributingtotheregulationoflipidmetabolismandinsulinsensitivity.SREBP-1cisanotherregulatorofAdiposegeneexpression,whichisinvolvedintheregulationofthebiosynthesisoffattyacidsandtriglycerides.SREBP-1cbindstotheAdiposepromoterandactivatesitstranscription,therebypromotinglipidsynthesisandstorage. FunctionofAdiposegene TheAdiposegenehasbeenshowntobeinvolvedinvariousaspectsofadipocytebiology,includingadipogenesis,lipidmetabolism,andinsulinsensitivity.Loss-of-functionstudieshavedemonstratedthatAdiposedeficiencyleadstoareductioninadipocytesizeandlipidcontent,aswellasanimpairmentofinsulinsignalingandglucoseuptakeinadipocytes.Incontrast,overexpressionofAdiposeinvitroandinvivoleadstoanincreaseinadipocytesizeandlipidcontent,aswella