FOSL2 promotes leptin gene expression in human and mouse adipocytes

Theadipocyte-derivedhormoneleptinisacriticalregulatorofmanyphysiologicalfunctions,�rangingfrom� satietytoimmunity.�Surprisingly,�verylittleisknownaboutthetranscriptionalpathwaysthatregulateadi- pocyte-specificexpressionofleptin.�Here,�wereportstudiesinwhichwepursuedastrategyintegratingBAC� transgenicreportermice,�reporterassays,�andchromatinstatemappingtolocateanadipocyte-specificcis-ele- mentupstreamoftheleptin�(LEP)�geneinhumanfatcells.�Quantitativeproteomicswithaffinityenrichment� ofprotein-DNAcomplexesidentifiedthetranscriptionfactorFOS-likeantigen�2�(FOSL2)�asbindingspecifi- callytotheidentifiedregion,�aresultthatwasconfirmedbyChIP.�KnockdownofFOSL2�inhumanadipocytes� decreasedLEPexpression,�andoverexpressionofFosl2�increasedLepexpressioninmouseadipocytes.�More- over,�theelevatedLEPexpressionobservedinobesitycorrelatedwellwithincreasedFOSL2�levelsinmiceand� humans,�andadipocyte-specificgeneticdeletionofFosl2�inmicereducedLepexpression.�Takentogether,�these� dataidentifyFOSL2�asacriticalregulatorofleptinexpressioninadipocytes.