Influence of biological sex and exercise on murine cardiac metabolism

Although the structural and functional effects of exercise on the heart are well established,the metabolic changes that occur in the heart during 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 session.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 glycerophospholipid 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.Immediately 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 cardiac 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.

Sampling strategy for estimating human exposure pathways to consumer chemicals

Human exposure to consumer chemicals has become a worldwide concern.In this work,a comprehensive sampling strategy is presented,to our knowledge being the first to study all relevant exposure pathways in a single cohort using multiple methods for assessment of exposure from each exposure pathway.The selected groups of chemicals to be studied are consumer chemicals whose production and use are currently in a state of transition and are;per-and polyfluorinated alkyl substances(PFASs),traditional and“emerging”brominated flame retardants(BFRs and EBFRs),organophosphate esters(OPEs)and phthalate esters(PEs).Information about human exposure to these contaminants is needed due to existing data gaps on human exposure intakes from multiple exposure pathways and relationships between internal and external exposure.Indoor environment,food and biological samples were collected from 61 participants and their households in the Oslo area(Norway)on two consecutive days,during winter 2013-14.Air,dust,hand wipes,and duplicate diet(food and drink)samples were collected as indicators of external exposure,and blood,urine,blood spots,hair,nails and saliva as indicators of internal exposure.A food diary,food frequency questionnaire(FFQ)and indoor environment questionnaire were also implemented.Approximately 2000 samples were collected in total and participant views on their experiences of this campaign were collected via questionnaire.While 91%of our participants were positive about future participation in a similar project,some tasks were viewed as problematic.Completing the food diary and collection of duplicate food/drink portions were the tasksmost frequent reported as“hard”/“very hard”.Nevertheless,a strong positive correlation between the reported total mass of food/drinks in the food record and the total weight of the food/drinks in the collection bottles was observed,being an indication of accurate performance of the participants despite the challenges of the sampling campaign.