Early metabolic alterations in pediatric obesity: Depot-specific insights from untargeted adipose tissue metabolomics

BACKGROUND: Childhood obesity is associated with lifelong metabolic risk, yet depot-specific alterations in adipose tissue metabolism during early life remain poorly understood. OBJECTIVE: This study aimed to characterize the metabolic differences between subcutaneous (sWAT) and visceral (vWAT) white adipose tissue in pediatric obesity using untargeted metabolomics. METHODS: Adipose tissue samples were collected from 12 children with overweight/obesity (OW/OB) and 18 who were of normal weight (NW). Untargeted metabolomics was performed using capillary electrophoresis-mass spectrometry to profile polar metabolites in sWAT and vWAT, and free fatty acids (FFAs) were analyzed using liquid chromatography-mass spectrometry. RESULTS: Comparison of children with OW/OB vs NW revealed pronounced depot-specific heterogeneity. vWAT in children with OW/OB exhibited 24 significantly altered metabolites compared with NW controls. This visceral profile was characterized by elevated ketone bodies (3-hydroxybutyrate and acetoacetic acid), tricarboxylic acid cycle intermediates (citric and pyruvic acids), and long-chain FFAs (palmitic and oleic acids). Concurrently, amino acid imbalances, specifically elevated leucine and arginine but reduced histidine and carnosine, suggested heightened mitochondrial stress and inflammation. In contrast, sWAT from children with OW/OB showed fewer variations (12 metabolites), defined primarily by elevated glutamate, leucine, and short-chain FFAs, reflecting a milder metabolic disruption. Direct comparison between depots revealed that vWAT was enriched in amino acids and carnitine, while sWAT showed relatively higher levels of glycolytic and ketone body intermediates in NW conditions. CONCLUSION: Depot-specific metabolic differences are evident in pediatric obesity. vWAT in children with OW/OB displays a metabolic profile consistent with heightened lipotoxicity and mitochondrial stress, whereas sWAT exhibits fewer, less pronounced metabolic differences.