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

• Published in: BMC medicine Vol. 21; no. 1; p. 176
• Main Authors: Azab, Sandi M, Shanmuganathan, Meera, de Souza, Russell J, Kroezen, Zachary, Desai, Dipika, Williams, Natalie C, Morrison, Katherine M, Atkinson, Stephanie A, Teo, Koon K, Azad, Meghan B, Simons, Elinor, Moraes, Theo J, Mandhane, Piush J, Turvey, Stuart E, Subbarao, Padmaja, Britz-McKibbin, Philip, Anand, Sonia S
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09.05.2023; BioMed Central; BMC
• Subjects: Adipose tissue; Adiposity; Age; Amino acids; Amino Acids, Aromatic; Analysis; Aromatic amino acids; Biomarkers; Body fat; Body mass; Body mass index; Body measurements; Body size; Body weight; Breastfeeding & lactation; Canada - epidemiology; Capillary electrophoresis; Care and treatment; Chain branching; Child; Child, Preschool; Childhood adiposity; Childhood overweight; Children; Children & youth; Cohort analysis; Complications and side effects; Cross-Sectional Studies; Electrophoresis; Fasting; Female; Females; Global health; Glutamates; Glutamic acid; Glutamine; Humans; Insulin resistance; Leucine; Lifestyles; Male; Males; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Metabolome; Metabolomics; NMR; Nuclear magnetic resonance; Nutrition research; Obesity; Obesity in children; Overweight; Overweight - epidemiology; Parent educational background; Pediatric Obesity - epidemiology; Phenotypes; Puberty; Public health; Replication; Scientific imaging; Serum metabolomics; Sex; Sex differences; Subgroups; Threonine; Waist circumference; Canada; Aromatic amino acids; Serum metabolomics; Waist circumference; Sex differences; Childhood overweight; Childhood adiposity
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-023-02886-8

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. 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). 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. 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.