Metabolic remodeling and the modulatory role of vitamin D deficiency in African American children and adolescents with obesity

Abstract Background Obesity is a complex metabolic condition with a disproportionate impact among African American youth. Metabolomic profiling enables high-resolution mapping of obesity-related biochemical changes across metabolic pathways. Methods We analyzed 551 African American pediatric participants (aged 2–21 years) recruited at the Children’s Hospital of Philadelphia between 2002 and 2020. Vitamin D deficiency was observed in 86 participants, including 62 of 309 individuals with overweight or obesity (20%). Plasma metabolites were quantified using the Nightingale NMR platform. Obesity was defined using age- and sex-specific BMI percentiles. Results A total of 142 individual metabolite markers and ratios were significantly associated with obesity (FDR < 0.05). Obesity‑related metabolic changes were characterized by elevated branched-chain and aromatic amino acids, GlycA, and triglyceride-rich VLDL subclasses, along with reduced Gly, large HDL particles, and cholesterol-enriched lipoproteins. Global enrichment analysis identified a significant overrepresentation of nominally significant interactions with vitamin D deficiency ( p < 2.2 × 10 − ¹⁶). Conclusions Obesity in African American youth is linked to widespread metabolic remodeling across amino acid, lipid, and inflammatory pathways, reflecting core features of cardiometabolic risk. Vitamin D status may also influence these responses, suggesting a potential role in modifying obesity-related risk. These findings highlight the importance of early identification and prevention strategies and point to vitamin D as a possible target for future investigation.