Although the structural and functional effects of exercise on the heart are well established,the metabolic changes that occur in the heart dur-ing and after exercise remain unclear.In this study,we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill exercise.After the exercise bout,we also recorded blood lactate,glucose,and ketone body levels and measured cardiac mitochondrial respiration.In both male and female mice,moderate-and high-intensity exercise acutely increased blood lactate levels.In both sexes,low-and moderate-intensity exercise augmented circulating 3-hydroxybutryrate levels immediately after the exercise bout;however,only in female mice did high-intensity exercise increase 3-hydroxybutyrate levels,with significant increases occurring 1 h after the exercise ses-sion.Untargeted metabolomics analyses of sedentary female and male hearts suggest considerable sex-dependent differences in basal cardiac metabolite levels,with female hearts characterized by higher levels of pantothenate,pyridoxamine,homoarginine,tryptophan,and several glyc-erophospholipid and sphingomyelin species and lower levels of numerous metabolites,including acetyl coenzyme A,glucuronate,gulonate,hydroxyproline,prolyl-hydroxyproline,carnosine,anserine,and carnitinylated and glycinated species,as compared with male hearts.Immedi-ately after a bout of treadmill exercise,both male and female hearts had higher levels of corticosterone;however,female mice showed more extensive exercise-induced changes in the cardiac metabolome,characterized by significant,time-dependent changes in amino acids(e.g.,serine,alanine,tyrosine,tryptophan,branched-chain amino acids)and the ketone body 3-hydroxybutyrate.Results from experiments using isolated car-diac mitochondria suggest that high-intensity treadmill exercise does not acutely affect respiration or mitochondrial coupling;however,female cardiac mitochondria demonstrate generally higher adenosine diphosphate sensitivity compared with male cardiac mitochondria.Collectively,these findings in mice reveal key sex-dependent differences in cardiac metabolism and suggest that the metabolic network in the female heart is more responsive to physiological stress caused by exercise.

Kyle Fulghum;Helen E.Collins;Steven P.Jones;Bradford G.Hill

Diabetes and Obesity Center,Department of Medicine,Division of Environmental Medicine,Christina Lee Brown Envirome Institute,University of Louisville,Louisville,KY 40202,USA;Department of Physiology,University of Louisville,Louisville,KY 40202,USA

运动与健康科学（英文）

[1]Kyle Fulghum;Helen E.Collins;Steven P.Jones;Bradford G.Hill-.Influence of biological sex and exercise on murine cardiac metabolism)[J].运动与健康科学（英文）,2022(04):479-494

hydroxybutryrate,pantothenate,pyridoxamine,homoarginine,glyc,erophospholipid,gulonate,anserine,carnitinylated,glycinated,Immedi

Influence,biological,exercise,murine,cardiac,metabolism,Although,structural,functional,effects,well,established,metabolic,changes,that,dur,after,remain,unclear,this,study,metabolomics,assess,dependent,metabolome,following,session,treadmill,After,bout,also,recorded,blood,lactate,glucose,ketone,body,levels,measured,mitochondrial,respiration,both,female,mice,moderate,intensity,acutely,increased,sexes,augmented,circulating,immediately,however,only,did,hydroxybutyrate,significant,increases,occurring,Untargeted,analyses,sedentary,hearts,suggest,considerable,differences,basal,characterized,by,higher,tryptophan,several,sphingomyelin,species,lower,numerous,metabolites,including,acetyl,coenzyme,glucuronate,hydroxyproline,prolyl,carnosine,compared,had,corticosterone,showed,more,extensive,induced,amino,acids,alanine,tyrosine,branched,chain,Results,from,experiments,using,isolated,does,not,affect,coupling,demonstrate,generally,adenosine,diphosphate,sensitivity,Collectively,these,findings,reveal,key,network,responsive,physiological,stress,caused

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