Effects of Proportions of Dietary Macronutrients on Glucocorticoid Metabolism in Diet-Induced Obesity in Rats 英文参考文献.docVIP

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Effects of Proportions of Dietary Macronutrients on Glucocorticoid Metabolism in Diet-Induced Obesity in Rats 英文参考文献.doc

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Effects of Proportions of Dietary Macronutrients on Glucocorticoid Metabolism in Diet-Induced Obesity in Rats 英文参考文献

EffectsofProportionsofDietaryMacronutrientson GlucocorticoidMetabolisminDiet-InducedObesityin Rats RolandH.Stimson1*,GeraldE.Lobley2,IoannaMaraki1,NicholasM.Morton1,RuthAndrew1,BrianR. Walker1 1CentreforCardiovascularSciences,Queen’sMedicalResearchInstitute,UniversityofEdinburgh,Edinburgh,UnitedKingdom,2DivisionofObesityandMetabolicHealth, RowettInstituteofNutritionandHealth,UniversityofAberdeen,Aberdeen,UnitedKingdom Abstract Tissueglucocorticoidlevelsintheliverandadiposetissueareregulatedbyregenerationofinactiveglucocorticoidby11b- hydroxysteroid dehydrogenase type 1 (11b-HSD1) and inactivation by 5a- and 5b-reductases. A low carbohydrate diet increaseshepatic11b-HSD1andreducesglucocorticoidmetabolismduringweightlossinobesehumans.Wehypothesized thatsimilarvariationsinmacronutrientproportionsregulateglucocorticoidmetabolisminobeserats.MaleListerHooded ratswerefedanobesity-inducingadlibitum‘Western’diet(37%fat,n=36)for22weeks,thenrandomisedtocontinuethis diet(n=12)ortoswitchtoeitheralowcarbohydrate(n=12)oramoderatecarbohydrate(n=12)dietforthefinal8weeks. A parallel lean control group were fed an ad libitum control diet (10% fat, n=12) throughout. The low and moderate carbohydrate diets decreased hepatic 11b-HSD1 mRNA compared with the Western diet (both 0.760.0 vs 0.960.1AU; p,0.01), but did not alter 11b-HSD1 in adipose tissue. 5a-Reductase mRNA was increased on the low carbohydrate compared with the moderate carbohydrate diet. Compared with lean controls, the Western diet decreased 11b-HSD1 activity(1.660.1vs2.860.1nmol/mcgprotein/hr;p,0.001)andincreased5a-reductaseand5b-reductasemRNAs(1.960.3 vs1.060.2and1.660.1vs1.060.1AUrespectively;p,0.01)intheliver,andreduced11b-HSD1mRNAandactivity(both p,0.01) in adipose tissue. Although an obesity-inducing high fat diet in rats recapitulates the abnormal glucocorticoid metabolismassociatedwithhumanobesityinliver(butnotinadiposetissue),alowcarbohydratedietdoesnotincrease hepatic11b-HSD1inobeseratsasoccursinhumans. Citation