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Tryptophan Metabolism Is Associated with BMI and Adipose Tissue Mass and Linked to Metabolic Disease in Pediatric Obesity
Authors:Julia Lischka  Andrea Schanzer  Margot Baumgartner  Charlotte de Gier  Susanne Greber-Platzer  Maximilian Zeyda
Affiliation:Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, 1190 Vienna, Austria; (J.L.); (A.S.); (M.B.); (C.d.G.); (S.G.-P.)
Abstract:The obesity epidemic has contributed to an escalating prevalence of metabolic diseases in children. Overnutrition leads to increased tryptophan uptake and availability. An association between the induction of the tryptophan catabolic pathway via indoleamine 2,3-dioxygenase (IDO) activity and obesity-related inflammation has been observed. This study aimed to investigate the impact of pediatric obesity on tryptophan metabolism and the potential relationship with metabolic disease. In this prospective cohort study, plasma kynurenine, tryptophan, and serotonin levels were measured by ELISA, and IDO activity was estimated by calculating the kynurenine/tryptophan ratio in a clinically characterized population with severe obesity (BMI ≥ 97th percentile) aged 9 to 19 (n = 125). IDO activity and its product kynurenine correlated with BMI z-score and body fat mass, whereas concentrations of serotonin, the alternative tryptophan metabolite, negatively correlated with these measures of adiposity. Kynurenine and tryptophan, but not serotonin levels, were associated with disturbed glucose metabolism. Tryptophan concentrations negatively correlated with adiponectin and were significantly higher in prediabetes and metabolically unhealthy obesity. In conclusion, BMI and body fat mass were associated with increased tryptophan catabolism via the kynurenine pathway and decreased serotonin production in children and adolescents with severe obesity. The resulting elevated kynurenine levels may contribute to metabolic disease in obesity.
Keywords:childhood   aromatic amino acids   inflammation   prediabetes   metabolically healthy obesity   indoleamine 2  3-dioxygenase
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