Exploring Metabolic Signatures: Unraveling the Association with Obesity in Children and Adolescents

Article

Exploring Metabolic Signatures: Unraveling the Association with Obesity in Children and Adolescents

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Diamanto Koutaki ¹, Garyfallia Stefanou ², Sofia-Maria Genitsaridi ¹, Eleni Ramouzi ¹, Athanasia Kyrkili ³, Meropi D. Kontogianni ³, Eleni Kokkou ¹, Eleni Giannopoulou ¹, Penio Kassari ^1,4 and Evangelia Charmandari  ^1,4,*

¹ Center for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’, Children’s Hospital, 11527 Athens, Greece
² ECONCARE—Health Research & Consulting, 11528 Athens, Greece
³ Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University of Athens, 17671 Athens, Greece
⁴ Division of Endocrinology and Metabolism, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece

^*Author to whom correspondence should be addressed.

Submission received: 15 April 2025 / Revised: 21 May 2025 / Accepted: 23 May 2025 / Published: 28 May 2025

Abstract

Background: Childhood obesity is a growing global health concern. Metabolomics, the comprehensive study of metabolites within biological systems, offers a powerful approach to better define the phenotype and understand the complex biochemical alterations associated with obesity. The aim of this systematic review was to summarize current knowledge in the field of metabolomics in childhood obesity and to identify metabolic signatures or biomarkers associated with overweight/obesity (Ov/Ob) and Metabolically Unhealthy Obesity (MUO) in children and adolescents. Methods: We performed a systematic search of Medline and Scopus databases according to PRISMA guidelines. We included only longitudinal prospective studies or randomized controlled trials with ≥12 months of follow-up, as well as meta-analyses of the above that assessed the relation between metabolic signatures related to obesity and Body Mass Index (BMI) or other measures of adiposity in children and adolescents aged 2–19 years with overweight or obesity. Initially, 595 records were identified from PubMed and 1565 from Scopus. After removing duplicates and screening for relevance, 157 reports were assessed for eligibility. From the additional search, 75 new records were retrieved, of which none were eligible for our study. Finally, 7 reports were included in the present systematic review (4 reporting on Ov/Ob and 4 on MUO). Results: The presented studies suggest that the metabolism of amino acids and lipids is primarily affected by childhood obesity. Metabolites like glycoprotein acetyls, the Apolipoprotein B/Apolipoprotein A-1 ratio, and lactate have emerged as potential biomarkers for insulin resistance and metabolic syndrome, highlighting their potential value in clinical applications. Conclusions: There is a need for future longitudinal studies to assess metabolic changes over time, interventional studies to evaluate the efficacy of therapeutic strategies, and large-scale population studies to explore metabolic diversity across different demographics. Our findings reveal specific biomarkers in the amino acid and lipid pathway that may serve as early indicators of childhood obesity and its associated cardiometabolic complications.

Keywords: metabolomics; metabolic signatures; metabolic biomarkers; childhood obesity