Metabolomic Signatures for the Effects of Weight Loss Interventions on Severe Obesity in Children and Adolescents

Abstract

Childhood obesity has increased worldwide, and many clinical and public interventions have attempted to reduce morbidity. We aimed to determine the metabolomic signatures associated with weight control interventions in children with obesity. Forty children from the "Intervention for Children and Adolescent Obesity via Activity and Nutrition (ICAAN)" cohort were selected according to intervention responses. Based on changes in body mass index z-scores, 20 were responders and the remaining non-responders. Their serum metabolites were quantitatively analyzed using capillary electrophoresis time-of-flight mass spectrometry at baseline and after 6 and 18 months of intervention. After 18 months of intervention, the metabolite cluster changes in the responders and non-responders showed a difference on the heatmap, but significant metabolites were not clear. However, regardless of the responses, 13 and 49 metabolites were significant in the group of children with obesity intervention at 6 months and 18 months post-intervention compared to baseline. In addition, the top five metabolic pathways (D-glutamine and D-glutamate metabolism; arginine biosynthesis; alanine, aspartate, and glutamate metabolism; TCA cycle (tricarboxylic acid cycle); valine, leucine, and isoleucine biosynthesis) including several amino acids in the metabolites of obese children after 18 months were significantly changed. Our study showed significantly different metabolomic profiles based on time post obesity-related intervention. Through this study, we can better understand and predict childhood obesity through metabolite analysis and monitoring.

Keywords: biomarkers; child; interventions; metabolomics; obesity; pediatric.

Figure 1

Plasma metabolome profiles of the study population. (A) Principal component analysis and (B) hierarchical cluster analysis showing time-dependent metabolic changes by weight-loss interventions rather than responsiveness to the intervention. (C) Volcano plots of significant metabolites (FDR adjusted p-value < 0.05, fold change > 1.2) at 6 months and 18 months post-intervention compared to baseline.

Figure 2

Enriched metabolite sets of significant metabolites between baseline and 18 months post-intervention on the basis of KEGG database.

Figure 3

Network mapping showing significantly changed metabolic pathways by weight-loss intervention after (A) 6 months and (B) 18 months. Node color indicates direction of changes (red, up; blue, down) or non-significance (gray).

Figure 4

Metabolic pathway changes by weight-loss intervention. (A) TCA cycle and (B) arginine biosynthesis and urea cycle. (Red, metabolites increased in plasma at 18 months post-intervention compared to at baseline; blue, metabolites decreased in plasma at 18 months post-intervention compared to at baseline).