Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis
Abstract 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 adiposi...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-023-02886-8 |
| _version_ | 1797827526922338304 |
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| author | Sandi M Azab Meera Shanmuganathan Russell J de Souza Zachary Kroezen Dipika Desai Natalie C Williams Katherine M Morrison Stephanie A Atkinson Koon K Teo Meghan B Azad Elinor Simons Theo J Moraes Piush J Mandhane Stuart E Turvey Padmaja Subbarao Philip Britz-McKibbin Sonia S Anand |
| author_facet | Sandi M Azab Meera Shanmuganathan Russell J de Souza Zachary Kroezen Dipika Desai Natalie C Williams Katherine M Morrison Stephanie A Atkinson Koon K Teo Meghan B Azad Elinor Simons Theo J Moraes Piush J Mandhane Stuart E Turvey Padmaja Subbarao Philip Britz-McKibbin Sonia S Anand |
| author_sort | Sandi M Azab |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T12:49:44Z |
| format | Article |
| id | doaj.art-af6d3e803bc74e65ac64b8014ecf71fc |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-04-09T12:49:44Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-af6d3e803bc74e65ac64b8014ecf71fc2023-05-14T11:19:18ZengBMCBMC Medicine1741-70152023-05-0121111010.1186/s12916-023-02886-8Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysisSandi M Azab0Meera Shanmuganathan1Russell J de Souza2Zachary Kroezen3Dipika Desai4Natalie C Williams5Katherine M Morrison6Stephanie A Atkinson7Koon K Teo8Meghan B Azad9Elinor Simons10Theo J Moraes11Piush J Mandhane12Stuart E Turvey13Padmaja Subbarao14Philip Britz-McKibbin15Sonia S Anand16Department of Medicine, McMaster UniversityDepartment of Chemistry and Chemical Biology, McMaster UniversityChanchlani Research Centre, McMaster UniversityDepartment of Chemistry and Chemical Biology, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityPopulation Health Research Institute, Hamilton Health SciencesDepartment of Pediatrics, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Pediatrics and Child Health, Children’s Hospital Research Institute of Manitoba, University of ManitobaDepartment of Pediatrics and Child Health, Children’s Hospital Research Institute of Manitoba, University of ManitobaDepartment of Pediatrics, Hospital for Sick ChildrenDepartment of Pediatrics, University of AlbertaDepartment of Pediatrics, BC Children’s Hospital, University of British ColumbiaDepartment of Medicine, McMaster UniversityDepartment of Chemistry and Chemical Biology, McMaster UniversityDepartment of Medicine, McMaster UniversityAbstract 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.https://doi.org/10.1186/s12916-023-02886-8Childhood overweightChildhood adiposityWaist circumferenceSerum metabolomicsSex differencesAromatic amino acids |
| spellingShingle | Sandi M Azab Meera Shanmuganathan Russell J de Souza Zachary Kroezen Dipika Desai Natalie C Williams Katherine M Morrison Stephanie A Atkinson Koon K Teo Meghan B Azad Elinor Simons Theo J Moraes Piush J Mandhane Stuart E Turvey Padmaja Subbarao Philip Britz-McKibbin Sonia S Anand Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis BMC Medicine Childhood overweight Childhood adiposity Waist circumference Serum metabolomics Sex differences Aromatic amino acids |
| title | Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis |
| title_full | Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis |
| title_fullStr | Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis |
| title_full_unstemmed | Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis |
| title_short | Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis |
| title_sort | early sex dependent differences in metabolic profiles of overweight and adiposity in young children a cross sectional analysis |
| topic | Childhood overweight Childhood adiposity Waist circumference Serum metabolomics Sex differences Aromatic amino acids |
| url | https://doi.org/10.1186/s12916-023-02886-8 |
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