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; 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.

A Metabolomics-Based Investigation of the Effects of a Short-Term Body Weight Reduction Program in a Cohort of Adolescents with Obesity: A Prospective Interventional Clinical Study

“…To the best of our knowledge, few interventional studies have investigated the reversibility of the metabolomic signature that characterizes childhood obesity [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. For instance, while one work did not detect any difference in the serum amino acid profile among children with obesity, measured before and after a 48-week exercise-based program [ 18 ], in a 1-year lifestyle intervention administered to a cohort of children with obesity, 17 metabolites were reported to be predictive of weight loss, including arginine, 1 lysophosphatidylcholine (LysPC a C18:0) and 15 long-chain and unsaturated phosphatidylcholines (13 diacyl and 2 acyl-alky PCs) [ 15 ].…”

“…For instance, while one work did not detect any difference in the serum amino acid profile among children with obesity, measured before and after a 48-week exercise-based program [ 18 ], in a 1-year lifestyle intervention administered to a cohort of children with obesity, 17 metabolites were reported to be predictive of weight loss, including arginine, 1 lysophosphatidylcholine (LysPC a C18:0) and 15 long-chain and unsaturated phosphatidylcholines (13 diacyl and 2 acyl-alky PCs) [ 15 ]. In a more recent 18-month weight loss intervention in a pediatric population, a cluster of 13 metabolites was identified to change at the end of the study, denoting the involvement of urea and tricarboxylic acid (TCA) cycles and several amino acid metabolic pathways (i.e., arginine, glutamine, glutamate, cysteine, and methionine) [ 19 ]. One limitation of these (even) long-lasting studies is the adoption of an out-patient setting, i.e., the enrolment of participants that followed physician-imparted instructions of lifestyle change at home, without the medical supervision that, instead, is ensured in an in-patient setting.…”

Subcutaneous Adipose Tissue Transcriptome Highlights Specific Expression Profiles in Severe Pediatric Obesity: A Pilot Study

“…However, it has been established that these mechanisms are impaired in patients with obesity [ 49 ]. For instance, Sohn and colleagues demonstrated that TCA metabolites were higher in children affected by obesity before 18 months of weight loss [ 50 ]. The catabolism of branched-chain amino acids (BCCAs) seems to play a central role in all the lipid and energetic pathways.…”

Childhood Obesity and the Cryptic Language of the Microbiota: Metabolomics’ Upgrading

“…Such science, therefore, has the potential to aid decision making in the field of personalized medicine [ 88 , 89 , 90 ]. Therefore, the identification of possible biomarkers in pediatric populations via metabolomics could provide an opportunity not only to better characterize this condition, but also to find new and more effective prevention and treatment approaches [ 91 ], allowing for tailor-made management [ 85 , 92 ]. The close correlation between microbiota and metabolomic analysis is schematized in Figure 1 .…”