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

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

doi:10.1186/s12916-023-02886-8

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

BMC Med. 2023 May 9;21(1):176. doi: 10.1186/s12916-023-02886-8.

Authors

Sandi M Azab^{1

2

3}, Meera Shanmuganathan⁴, Russell J de Souza^{3

5

6}, Zachary Kroezen⁴, Dipika Desai^{1

6}, Natalie C Williams^{1

3}, Katherine M Morrison^{6

7

8}, Stephanie A Atkinson⁸, Koon K Teo^{1

6}, Meghan B Azad⁹, Elinor Simons⁹, Theo J Moraes¹⁰, Piush J Mandhane¹¹, Stuart E Turvey¹², Padmaja Subbarao^{1

10}, Philip Britz-McKibbin⁴, Sonia S Anand^{13

14

15

16}

Affiliations

¹ Department of Medicine, McMaster University, Hamilton, ON, Canada.
² Department of Pharmacognosy, Alexandria University, Alexandria, Egypt.
³ Chanchlani Research Centre, McMaster University, Hamilton, Canada.
⁴ Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada.
⁵ Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
⁶ Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada.
⁷ Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada.
⁸ Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
⁹ Department of Pediatrics and Child Health, Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada.
¹⁰ Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada.
¹¹ Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
¹² Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
¹³ Department of Medicine, McMaster University, Hamilton, ON, Canada. anands@mcmaster.ca.
¹⁴ Chanchlani Research Centre, McMaster University, Hamilton, Canada. anands@mcmaster.ca.
¹⁵ Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada. anands@mcmaster.ca.
¹⁶ Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada. anands@mcmaster.ca.

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.

Keywords: Aromatic amino acids; Childhood adiposity; Childhood overweight; Serum metabolomics; Sex differences; Waist circumference.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adiposity
Amino Acids, Aromatic
Canada / epidemiology
Child
Child, Preschool
Cross-Sectional Studies
Female
Glutamates
Glutamine
Humans
Male
Metabolome
Overweight* / epidemiology
Pediatric Obesity* / epidemiology

Substances

Glutamine
Amino Acids, Aromatic
Glutamates

Grants and funding

MWG-146332/Canadian Institutes for Health Research