Mechanisms of triglyceride accumulation in activated macrophages

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: LPS;    zymosan;    toll‐;    like receptors;    glucose;    fatty acid;    oxidation;   

DOI  :  10.1189/jlb.1111537

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

LPStreatmentofmacrophagesinducesTGaccumulation,whichisaccentuatedbyTG‐richlipoproteinsorFFA.WedefinedpathwaysalteredduringmacrophageactivationthatcontributetoTGaccumulation.Glucoseuptakeincreasedwithactivation,accompaniedbyincreasedGLUT1.Oxidationofglucosemarkedlydecreased,whereasincorporationofglucose‐derivedcarbonintoFAandsterolsincreased.MacrophageactivationalsoincreaseduptakeofFFA,associatedwithanincreaseinCD36.OxidationofFAwasmarkedlyreduced,whereastheincorporationofFAintoTGsincreased,associatedwithincreasedGPAT3andDGAT2.Additionally,macrophageactivationdecreasedTGlipolysis;however,expressionofATGLorHSLwasnotaltered.MacrophageactivationalteredgeneexpressionsimilarlywhenincubatedwithexogenousFAorAcLDL.WhereasactivationwithligandsofTLR2(zymosan),TLR3(polyI:C),orTLR4(LPS)inducedalterationsinmacrophagegeneexpression,leadingtoTGaccumulation,treatmentofmacrophageswithcytokineshadminimaleffects.Thus,activationofTLRsleadstoaccumulationofTGinmacrophagesbymultiplepathwaysthatmayhavebeneficialeffectsinhostdefensebutcouldcontributetotheacceleratedatherosclerosisinchronicinfectionsandinflammatorydiseases...

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