Investigating the kynurenine pathway in pediatric metabolic health

Objectives: The rise in obesity has led to a higher incidence of metabolic diseases in children. Overnutrition leads to increased intake and availability of tryptophan (TRP). Research indicates a link between indoleamine 2,3-dioxygenase (IDO) activity, the activation of the tryptophan catabolic pathway, and inflammation associated with obesity. This study investigated how pediatric obesity affects tryptophan metabolism and its potential link to metabolic syndrome. Methods: This prospective cohort study included 86 children aged 10 years and older, 56 of whom were obese. Obese children with body mass index (BMI) >95th percentile were divided into two groups: obese (BMI greater than 120 % of the 95th percentile for age and sex) and severely obese (BMI greater than 140 % of the 95th percentile for age and sex). Serum levels of kynurenine pathway metabolites were determined by liquid chromatography-mass spectrometry/mass spectrometry system. Results: The mean ages (13.6 and 13.2 years) and gender distribution (36.7 and 46.2 % male) were similar across the groups. There were significant differences in tryptophan levels between the groups, being higher in the obese groups (p<0.001). 3-hydroxykynurenine (3HK) was significantly higher in the obese group (p=0.029). 3-hydroxykynurenine/kynurenine (3HK/KYN) ratio also significantly correlated with increased GGT and triglyceride levels and low HDL. Also higher 3HK/KYN ratio was correlated with elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels. No significant relationship was found between the KYN/TRP ratio and obesity metabolic syndrome indicators. Conclusions: Although plasma kynurenine pathway metabolites showed some changes in children with obesity, larger series studies are needed to determine the relationship with metabolic syndrome.