Maternal Obesity during Gestation Impairs Fatty Acid Oxidation and Mitochondrial SIRT3 Expression in Rat Offspring at Weaning 英文参考文献.docVIP

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Maternal Obesity during Gestation Impairs Fatty Acid Oxidation and Mitochondrial SIRT3 Expression in Rat Offspring at Weaning 英文参考文献.doc

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Maternal Obesity during Gestation Impairs Fatty Acid Oxidation and Mitochondrial SIRT3 Expression in Rat Offspring at Weaning 英文参考文献

MaternalObesityduringGestationImpairsFattyAcid OxidationandMitochondrialSIRT3ExpressioninRat OffspringatWeaning SarahJ.Borengasser1,4,FranchescaLau4,PingKang4,MichaelL.Blackburn3,4,MartinJ.J.Ronis2,4 , ThomasM.Badger1,3,4,KartikShankar1,2,4 * 1DepartmentofPediatrics,UniversityofArkansasforMedicalSciences,LittleRock,Arkansas,UnitedStatesofAmerica,2DepartmentofPharmacologyandToxicology, UniversityofArkansasforMedicalSciences,LittleRock,Arkansas,UnitedStatesofAmerica,3DepartmentofPhysiologyandBiophysics,UniversityofArkansasforMedical Sciences,LittleRock,Arkansas,UnitedStatesofAmerica,4ArkansasChildren’sNutritionCenter,LittleRock,Arkansas,UnitedStatesofAmerica Abstract Inuteroexposuretomaternalobesityincreasestheoffspring’sriskofobesityinlaterlife.Wehavealsopreviouslyreported thatoffspringofobeseratdamsdevelophepaticsteatosis,mildhyperinsulinemia,andalipogenicgenesignatureinthe liveratpostnatalday(PND)21.Inthecurrentstudy,weexaminedsystemicandhepaticadaptationsinmaleSprague-Dawley offspringfromleanandobesedamsatPND21.Indirectcalorimetryrevealeddecreasesinenergyexpenditure(p,0.001)and increases in RER values (p,0.001), which were further exacerbated by high fat diet (45% kcals from fat) consumption indicatinganimpairedabilitytoutilizefattyacidsinoffspringofobesedamsasanalyzedbyPRCF.Mitochondrialfunctionis knowntobeassociatedwithfattyacidoxidation(FAO)intheliver.Severalmarkersofhepaticmitochondrialfunctionwere reducedinoffspringofobesedams.TheseincludedSIRT3mRNA(p=0.012)andmitochondrialproteincontent(p=0.002), electrontransportchaincomplexes(II,III,andATPase),andfastingPGC-1amRNAexpression(p,0.001).Moreover,hepatic LCAD, a SIRT3 target, was not only reduced 2-fold (p,0.001) but was also hyperacetylated in offspring of obese dams (p,0.005) suggesting decreased hepatic FAO. In conclusion, exposure to maternal obesity contributes to early perturbations in whole body and liver energy metabolism. Mitochondrial dysfunction may be an underlying event that reduceshepaticfattya