Adult-Onset Obesity Reveals Prenatal Programming of Glucose-Insulin Sensitivity in Male Sheep Nutrient Restricted during Late Gestation 英文参考文献.docVIP

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Adult-Onset Obesity Reveals Prenatal Programming of Glucose-Insulin Sensitivity in Male Sheep Nutrient Restricted during Late Gestation 英文参考文献.doc

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Adult-Onset Obesity Reveals Prenatal Programming of Glucose-Insulin Sensitivity in Male Sheep Nutrient Restricted during Late Gestation 英文参考文献

Adult-OnsetObesityRevealsPrenatalProgrammingof Glucose-InsulinSensitivityinMaleSheepNutrient RestrictedduringLateGestation PhilipRhodes1,JimCraigon2,ClintGray1,StuartM.Rhind3,PaulT.Loughna1,DavidS.Gardner1* 1SchoolofVeterinaryMedicineandScience,UniversityofNottingham,SuttonBonington,UnitedKingdom,2SchoolofBiosciences,UniversityofNottingham,Sutton Bonington,UnitedKingdom,3MacaulayLandUseResearchInstitute,Craigiebuckler,Aberdeen,UnitedKingdom Abstract Background: Obesity invokes a range of metabolic disturbances, but the transition from a poor to excessive nutritional environment may exacerbate adult metabolic dysfunction. The current study investigated global maternal nutrient restrictionduringearlyorlategestationonglucosetoleranceandinsulinsensitivityintheadultoffspringwhenleanand obese. Methods/Principal Findings: Pregnant sheep received adequate (1.0M; CE, n=6) or energy restricted (0.7M) diet during early(1–65days;LEE,n=6)orlate(65–128days;LEL,n=7)gestation(term,147days).Subsequentoffspringremainedon pasture until 1.5 years when all received glucose and insulin tolerance tests (GTT ITT) and body composition determinationbydualenergyx-rayabsorptiometry(DXA).Allanimalswerethenexposedtoanobesogenicenvironmentfor 6–7monthsandallprotocolsrepeated.Prenataldietarytreatmenthadnoeffectonbirthweightoronmetabolicendpoints when animals were ‘lean’ (1.5 years). Obesity revealed generalised metabolic ‘inflexibility’ and insulin resistance; characterisedbybluntedexcursionsofplasmaNEFAandincreasedinsulinAUC(from133to341[s.e.d.26]ng.ml21.120mins) duringaGTT,respectively.ForLELvs.CE,thepeakinplasmainsulinwhenobesewasgreater(7.8vs.4.7[s.e.d.1.1]ng.ml21) andwasexacerbatedbyoffspringsex(i.e.9.8vs.4.4[s.e.d.1.16]ng.ml21;LELmalevs.CEmale,respectively).Acquisitionof obesity also significantly influenced the plasma lipid and protein profile to suggest, overall, greater net lipogenesis and reducedproteinmetabolism. Conclusions:Thisstudyindicatesgeneralisedmetabolicdysfunctionwithadult