Tan, K. M.-L., Tint, M.-T., Kothandaraman, N., Yap, F., Godfrey, K. M., Lee, Y. S., Tan, K. H., Gluckman, P. D., Chong, Y.-S., Chong, M. F. F., Eriksson, J. G., & Cameron-Smith, D. (2022). Association of plasma kynurenine pathway metabolite concentrations with metabolic health risk in prepubertal Asian children. International Journal of Obesity. https://doi.org/10.1038/s41366-022-01085-4
Abstract:
Background
The tryptophan-kynurenine (KYN) pathway is linked to obesity-related systemic inflammation and metabolic health. The pathway generates multiple metabolites, with little available data on their relationships to early markers of increased metabolic disease risk in children. The aim of this study was to examine the association of multiple KYN pathway metabolites with metabolic risk markers in prepubertal Asian children.
Methods
Fasting plasma concentrations of KYN pathway metabolites were measured using liquid chromatography-tandem mass spectrometry in 8-year-old children (n = 552) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) prospective mother-offspring cohort study. The child’s weight and height were used to ascertain overweight and obesity using local body mass index (BMI)-for-age percentile charts. Body fat percentage was measured by quantitative magnetic resonance. Abdominal circumference, systolic and diastolic blood pressure, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, and HDL-cholesterol were used for the calculation of Metabolic syndrome scores (MetS). Serum triglyceride, BMI, gamma-glutamyl transferase (GGT), and abdominal circumference were used in the calculation of the Fatty liver index (FLI). Associations were examined using multivariable regression analyses.
Results
In overweight or obese children (n = 93; 16.9% of the cohort), all KYN pathway metabolites were significantly increased, relative to normal weight children. KYN, kynurenic acid (KA), xanthurenic acid (XA), hydroxyanthranilic acid (HAA) and quinolinic acid (QA) all showed significant positive associations with body fat percentage (B(95% CI) = 0.32 (0.22,0.42) for QA), HOMA-IR (B(95% CI) = 0.25 (0.16,0.34) for QA), and systolic blood pressure (B(95% CI) = 0.14(0.06,0.22) for QA). All KYN metabolites except 3-hydroxykynurenine (HK) significantly correlated with MetS (B (95% CI) = 0.29 (0.21,0.37) for QA), and FLI (B (95% CI) = 0.30 (0.21,0.39) for QA).
Conclusions
Higher plasma concentrations of KYN pathway metabolites are associated with obesity and with increased risk for metabolic syndrome and fatty liver in prepubertal Asian children.
License type:
Publisher Copyright
Funding Info:
This research / project is supported by the Singapore Ministry of Health’s National Medical Research Council (NMRC) - Open Fund-Large Collaborative Grant
Grant Reference no. : MOH-000504
This research / project is supported by the National Research Foundation (NRF) - Human Potential Programme
Grant Reference no. : SP/F/21/150013