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ClodronateLiposomesImproveMetabolicProfileand
ReduceVisceralAdiposeMacrophageContentin
Diet-InducedObeseMice
BinFeng1,3,PingJiao3,YaohuiNie3,ThomasKim3,DaleJun3,NicovanRooijen2,ZaiqingYang1,Haiyan
Xu3*
1KeyLaboratoryofAgriculturalAnimalics,BreedingandReproductionofMinistryofEducation,CollegeofLifeScienceandTechnology,HuazhongAgricultural
University,Wuhan,China,2DepartmentofMolecularCellBiology,FacultyofMedicine,VrijeUniversiteit,Amsterdam,herlands,3AlpertMedicalSchool,Hallett
CenterforDiabetesandEndocrinology,BrownUniversity,Providence,RhodeIsland,UnitedStatesofAmerica
Abstract
Background:Obesity-relatedadiposeinflammationhasbeenthoughttobeacausalfactorforthedevelopmentofinsulin
resistanceandtype2diabetes.Infiltratedmacrophagesinadiposetissueofobeseanimalsandhumansareanimportant
sourceforinflammatorycytokines.Clodronateliposomescanablatemacrophagesbyinducingapoptosis.Inthisstudy,we
aimtodeterminewhetherperitonealinjectionofclodronateliposomeshasanybeneficialeffectonsystemicglucose
homeostasis/insulinsensitivityandwhethermacrophagecontentinvisceraladiposetissuewillbereducedindiet-induced
obese(DIO)mice.
Methodology/PrincipalFindings:ClodronateliposomeswereusedtodepletemacrophagesinleanandDIOmice.
Macrophagecontentinvisceraladiposetissue,metabolicparameters,glucoseandinsulintolerance,adiposeandliver
histology,adipokineandcytokineproductionwereexamined.Hyperinsulinemic-euglycemicclampstudywasalso
performedtoassesssystemicinsulinsensitivity.Peritonealinjectionofclodronateliposomessignificantlyreducedblood
glucoseandinsulinlevelsinDIOmice.Systemicglucosetoleranceandinsulinsensitivityweremildlyimprovedinbothlean
andDIOmicetreatedwithclodronateliposomesbyintraperitoneal(ip)injection.Hepatosteatosiswasdramatically
alleviatedandsuppressionofhepaticglucoseoutputwasmarkedlyincreasedinDIOmicetreatedwithclodronate
liposomes.MacrophagecontentinvisceraladiposetissueofDIOmicewaseffectivelydecreasedwithoutaffecting
subcutaneousadiposetissue.Interestingly,levelsofinsulinsensitizinghormoneadiponectin,includingthehighmolecular
weightform,weresignificantlyelevatedincirculation.
Conclusions/Significance:Intraperitonealinjectionofclodronateliposomesreducesvisceraladiposetissuemacrophages,
improvessystemicglucosehomeostasisandinsulinsensitivityinDIOmice,whichcanbepartiallyattributabletoincreased
adiponectinlevels.
Citation:FengB,JiaoP,NieY,KimT,JunD,etal.(2011)ClodronateLiposomesImproveMetabolicProfileandReduceVisceralAdiposeMacrophageContentin
Diet-InducedObeseMice.PLoSONE6(9):e24358.doi:10.1371/journal.pone.00内容来自淘豆网www.taodocs.com转载请标明出处.
ClodronateLiposomesImproveMetabolicProfileand
ReduceVisceralAdiposeMacrophageContentin
Diet-InducedObeseMice
BinFeng1,3,PingJiao3,YaohuiNie3,ThomasKim3,DaleJun3,NicovanRooijen2,ZaiqingYang1,Haiyan
Xu3*
1KeyLaboratoryofAgriculturalAnimalics,BreedingandReproductionofMinistryofEducation,CollegeofLifeScienceandTechnology,HuazhongAgricultural
University,Wuhan,China,2DepartmentofMolecularCellBiology,FacultyofMedicine,VrijeUniversiteit,Amsterdam,herlands,3AlpertMedicalSchool,Hallett
CenterforDiabetesandEndocrinology,BrownUniversity,Providence,RhodeIsland,UnitedStatesofAmerica
Abstract
Background:Obesity-relatedadiposeinflammationhasbeenthoughttobeacausalfactorforthedevelopmentofinsulin
resistanceandtype2diabetes.Infiltratedmacrophagesinadiposetissueofobeseanimalsandhumansareanimportant
sourceforinflammatorycytokines.Clodronateliposomescanablatemacrophagesbyinducingapoptosis.Inthisstudy,we
aimtodeterminewhetherperitonealinjectionofclodronateliposomeshasanybeneficialeffectonsystemicglucose
homeostasis/insulinsensitivityandwhethermacrophagecontentinvisceraladiposetissuewillbereducedindiet-induced
obese(DIO)mice.
Methodology/PrincipalFindings:ClodronateliposomeswereusedtodepletemacrophagesinleanandDIOmice.
Macrophagecontentinvisceraladiposetissue,metabolicparameters,glucoseandinsulintolerance,adiposeandliver
histology,adipokineandcytokineproductionwereexamined.Hyperinsulinemic-euglycemicclampstudywasalso
performedtoassesssystemicinsulinsensitivity.Peritonealinjectionofclodronateliposomessignificantlyreducedblood
glucoseandinsulinlevelsinDIOmice.Systemicglucosetoleranceandinsulinsensitivityweremildlyimprovedinbothlean
andDIOmicetreatedwithclodronateliposomesbyintraperitoneal(ip)injection.Hepatosteatosiswasdramatically
alleviatedandsuppressionofhepaticglucoseoutputwasmarkedlyincreasedinDIOmicetreatedwithclodronate
liposomes.MacrophagecontentinvisceraladiposetissueofDIOmicewaseffectivelydecreasedwithoutaffecting
subcutaneousadiposetissue.Interestingly,levelsofinsulinsensitizinghormoneadiponectin,includingthehighmolecular
weightform,weresignificantlyelevatedincirculation.
Conclusions/Significance:Intraperitonealinjectionofclodronateliposomesreducesvisceraladiposetissuemacrophages,
improvessystemicglucosehomeostasisandinsulinsensitivityinDIOmice,whichcanbepartiallyattributabletoincreased
adiponectinlevels.
Citation:FengB,JiaoP,NieY,KimT,JunD,etal.(2011)ClodronateLiposomesImproveMetabolicProfileandReduceVisceralAdiposeMacrophageContentin
Diet-InducedObeseMice.PLoSONE6(9):e24358.doi:10.1371/journal.pone.00内容来自淘豆网www.taodocs.com转载请标明出处.
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发布于 : 2021-08-17
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