Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans 英文参考文献.docVIP

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Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans 英文参考文献.doc

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Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans 英文参考文献

o PL SMEDICINE CalorieRestrictionIncreasesMuscle MitochondrialBiogenesisinHealthyHumans Anthony E.Civitarese*,Stacy Carling, Leonie K.Heilbronn, Mathew H.Hulver, Barbara Ukropcova, Walter A.Deutsch, Steven R.Smith, Eric Ravussin forthe CALERIE Pennington Team PenningtonBiomedicalResearchCenter,BatonRouge,Louisiana,UnitedStatesofAmerica Funding:Thisstudywassupported byRO1AG20478(ER),andpartlyby aCNRUCenterGrant#1P30 ABSTRACT DK072476entitledNutritional Programming:Environmentaland MolecularInteractions.Thefunders hadnoroleinstudydesign,data collectionandanalysis,decisionto publish,orpreparationofthe manuscript. Background Caloricrestrictionwithoutmalnutritionextendslifespaninarangeoforganismsincluding insects and mammals and lowers free radical production by the mitochondria.However, the mechanismresponsibleforthisadaptationarepoorlyunderstood. CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. MethodsandFindings The current study was undertaken to examine muscle mitochondrial bioenergetics in responsetocaloricrestrictionaloneorincombinationwithexercisein36young(36.861.0y), overweight (body mass index, 27.8 6 0.7 kg/m2) individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX), 12.5% CR t 12.5% increased energyexpenditure(EE).Inthecontrols,24-hEEwasunchanged,butinCRandCREXitwas significantlyreducedfrombaselineevenafteradjustmentforthelossofmetabolicmass(CR, à135642kcal/d,p?0.002andCREX,à117652kcal/d,p?0.008).ParticipantsintheCRand CREXgroupshadincreasedexpressionofgenesencodingproteinsinvolvedinmitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p , 0.05). In parallel, mitochondrialDNAcontentincreasedby35%65%intheCRgroup(p?0.005)and21%64% intheCREXgroup(p,0.004),withnochangeinthecontrolgroup(2%62%).However,the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid) cycle (ci