Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis

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dc.contributor.authorAzab, Sandi M.
dc.contributor.authorShanmuganathan, Meera
dc.contributor.authorde Souza, Russell J.
dc.contributor.authorKroezen, Zachary
dc.contributor.authorDesai, Dipika
dc.contributor.authorWilliams, Natalie C.
dc.contributor.authorMorrison, Katherine M.
dc.contributor.authorAtkinson, Stephanie A.
dc.contributor.authorTeo, Koon K.
dc.contributor.authorAzad, Meghan B.
dc.contributor.authorSimons, Elinor
dc.contributor.authorMoraes, Theo J.
dc.contributor.authorMandhane, Piush J.
dc.contributor.authorTurvey, Stuart E.
dc.contributor.authorSubbarao, Padmaja
dc.contributor.authorBritz-McKibbin, Philip
dc.contributor.authorAnand, Sonia S.
dc.date.accessioned2023-06-01T17:50:59Z
dc.date.available2023-06-01T17:50:59Z
dc.date.issued2023-05-09
dc.date.updated2023-06-01T03:27:48Z
dc.description.abstractAbstract Background Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. Methods Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). Results In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20–28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. Conclusions Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males.en_US
dc.identifier.citationBMC Medicine. 2023 May 09;21(1):176
dc.identifier.citationBMC Medicine. 2023 May 09;21(1):176
dc.identifier.citationBMC Medicine. 2023 May 09;21(1):176
dc.identifier.citationBMC Medicine. 2023 May 09;21(1):176
dc.identifier.citationBMC Medicine. 2023 May 09;21(1):176
dc.identifier.citationBMC Medicine. 2023 May 09;21(1):176
dc.identifier.doi10.1186/s12916-023-02886-8
dc.identifier.urihttp://hdl.handle.net/1993/37368
dc.language.isoengen_US
dc.language.rfc3066en
dc.publisherBioMed Central (BMC)en_US
dc.rightsopen accessen_US
dc.rights.holderThe Author(s)
dc.subjectchildhood overweighten_US
dc.subjectchildhood adiposityen_US
dc.subjectwaist circumferenceen_US
dc.subjectserum metabolomicsen_US
dc.subjectsex differencesen_US
dc.subjectaromatic amino acidsen_US
dc.titleEarly sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysisen_US
dc.typejournal articleen_US
local.author.affiliationRady Faculty of Health Sciences::Max Rady College of Medicine::Department of Pediatrics and Child Healthen_US
oaire.awardNumberMWG-146332en_US
oaire.awardTitleGrant MWGen_US
oaire.citation.issue1en_US
oaire.citation.startPage176en_US
oaire.citation.titleBMC Medicineen_US
oaire.citation.volume21en_US
project.funder.identifierhttps://doi.org/10.13039/501100000024en_US
project.funder.nameCanadian Institutes of Health Researchen_US
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