Mice Chronically Fed High-Fat Diet Have Increased Mortality and Disturbed Immune Response in Sepsis 英文参考文献.docVIP

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Mice Chronically Fed High-Fat Diet Have Increased Mortality and Disturbed Immune Response in Sepsis 英文参考文献.doc

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Mice Chronically Fed High-Fat Diet Have Increased Mortality and Disturbed Immune Response in Sepsis 英文参考文献

MiceChronicallyFedHigh-FatDietHaveIncreased MortalityandDisturbedImmuneResponseinSepsis LouiseStrandberg1,MargaretaVerdrengh2,MariaEnge1,NiklasAndersson1,SylvieAmu2¤a ,Karin Onnheim¨ 2,AnnaBenrick1¤b,MikaelBrisslert2,JohanBylund2,MariaBokarewa2,StaffanNilsson3 ,John- OlovJansson1* 1Institute of Neuroscience and Physiology/Endocrinology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden, 2Department of RheumatologyandInflammationResearch,UniversityofGothenburgandSahlgrenskaUniversityHospital,Gothenburg,Sweden,3DepartmentofMathematicalStatistics, ChalmersUniversityofTechnology,Gothenburg,Sweden Abstract Background: Sepsis is a potentially deadly disease that often is caused by gram-positive bacteria, in particular Staphylococcusaureus(S.aureus).Astherearefeweffectivetherapiesforsepsis,increasedbasicknowledgeaboutfactors predisposingisneeded. Methodology/PrincipalFindings:ThepurposeofthisstudywastostudytheeffectofWesterndietonmortalityinducedby intravenous S. aureus inoculation and the immune functions before and after bacterial inoculation. Here we show that C57Bl/6miceonhigh-fatdiet(HFD)for8weeks,likegeneticallyobeseOb/Obmiceonlow-fatdiet(LFD),haveincreased mortalityduringS.aureus-inducedsepsiscomparedwithLFD-fedC57Bl/6controls.Bacterialloadinthekidneys5–7days afterinoculationwasincreased10-foldinHFD-fedcomparedwithLFD-fedmice.Atthattime,HFD-fedmicehadincreased serumlevelsandfatmRNAexpressionoftheimmunesuppressingcytokinesinterleukin-1receptorantagonist(IL-1Ra)and IL-10 comparedwith LFD-fed mice. Inaddition, HFD-fed mice had increased serum levels ofthe pro-inflammatory IL-1b. Also,HFD-fedmicewithandwithoutinfectionhadincreasedlevelsofmacrophagesinfat.Theproportionandfunctionof phagocytosinggranulocytes,andtheproductionofreactiveoxygenspecies(ROS)byperitoneallavagecellsweredecreased inHFD-fedcomparedwithLFD-fedmice. Conclusions:OurfindingsimplythatchronicHFDdisturbseveralinnateimmunefunctionsinmice,andimpairstheability toclearS.au