Carboxylesterase1Esterase-x Regulates Chylomicron Production in Mice 英文参考文献.docVIP

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Carboxylesterase1Esterase-x Regulates Chylomicron Production in Mice 英文参考文献.doc

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Carboxylesterase1Esterase-x Regulates Chylomicron Production in Mice 英文参考文献

Carboxylesterase1/Esterase-xRegulatesChylomicron ProductioninMice ArielD.Quiroga1,2,JihongLian1,2,RichardLehner1,2,3 * 1GrouponMolecularandCellBiologyofLipids,UniversityofAlberta,Edmonton,Alberta,Canada,2DepartmentofPediatrics,UniversityofAlberta,Edmonton,Alberta, Canada,3DepartmentofCellBiology,MazankowskiAlbertaHeartInstitute,UniversityofAlberta,Edmonton,Alberta,Canada Abstract Elevated postprandial plasma triacylglycerol (TG) concentrations are commonly associated with obesity and the risk of cardiovasculardisease.Dietaryfatcontributestothisconditionthroughtheproductionofchylomicrons.Carboxylesterases have been mainly studied for their role in drug metabolism, but recently they have been shown to participate in lipid metabolism; however, their role in intestinal lipid metabolism is unknown. Carboxylesterase1/esterase-x (Ces1/Es-x) deficientmicebecomeobese,hyperlipidemicanddevelophepaticsteatosisevenonstandardchowdiet.Here,weaimedto explore the role of Ces1/Es-x in intestinal lipid metabolism. Six-month old wild-type and Ces1/Es-x deficient mice were maintained on chow diet and intestinal lipid metabolism and plasma chylomicron clearance were analyzed. Along the intestineCes1/Es-xproteinisexpressedonlyinproximaljejunum.AblationofCes1/Es-xexpressionresultsinpostprandial hyperlipidemiaduetoincreasedsecretionofchylomicrons.Thesecretedchylomicronshaveaberrantproteincomposition, whichresultsintheirreducedclearance.Inconclusion,Ces1/Es-xparticipatesintheregulationofchylomicronassemblyand secretion. Ces1/Es-x might act as a lipid sensor in enterocytes regulating chylomicron secretion rate. Ces1/Es-x might represent an attractive pharmacological target for the treatment of lipid abnormalities associated with obesity, insulin resistanceandfattyliverdisease. Citation: Quiroga AD, Lian J,Lehner R(2012) Carboxylesterase1/Esterase-x RegulatesChylomicronProduction in Mice. PLoS ONE 7(11): e49515. doi:10.1371/ journal.pone.0049515 Editor:AntonioMoschetta,UniversityofBariConsor