Karen Mei-Ling Tan1,2, Mya-Thway Tint1,3, Narasimhan Kothandaraman1, Fabian Yap4,5,6, Keith M Godfrey7,8, Yung Seng Lee1,9,10, Kok Hian Tan4,11, Peter D Gluckman1,12, Yap-Seng Chong1,13, Mary F F Chong1,14, Johan G Eriksson1,3,13,15,16, David Cameron-Smith17,18. 1. Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. 2. Department of Laboratory Medicine, National University Hospital, Singapore, Singapore. 3. Human Potential Translational Research Programme, Yong Loo Lin School of Medicine (YLLSOM), National University of Singapore, Singapore, Singapore. 4. Duke-National University of Singapore (NUS) Medical School, Singapore, Singapore. 5. Department of Pediatric Endocrinology, KK Women's and Children's Hospital, Singapore, Singapore. 6. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. 7. MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK. 8. NIHR Southampton Biomedical Research Centre, University of Southampton and University of Southampton Hospital, Southampton, UK. 9. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 10. Khoo Teck Puat - National University Children's Medical Institute (KTPCMI), National University Health System, Singapore, Singapore. 11. Perinatal Audit and Epidemiology, Department of Maternal Fetal Medicine, KK Women's and Children's Hospital, Singapore, Singapore. 12. Liggins Institute, University of Auckland, Auckland, New Zealand. 13. Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine (YLLSOM), National University of Singapore, Singapore, Singapore. 14. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore. 15. Folkhälsan Research Center, Helsinki, Finland. 16. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland. 17. Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. DCameron_Smith@sics.a-star.edu.sg. 18. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. DCameron_Smith@sics.a-star.edu.sg.
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.
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.
Authors: Edward Yu; Christopher Papandreou; Miguel Ruiz-Canela; Marta Guasch-Ferre; Clary B Clish; Courtney Dennis; Liming Liang; Dolores Corella; Montserrat Fitó; Cristina Razquin; José Lapetra; Ramón Estruch; Emilio Ros; Montserrat Cofán; Fernando Arós; Estefania Toledo; Lluis Serra-Majem; José V Sorlí; Frank B Hu; Miguel A Martinez-Gonzalez; Jordi Salas-Salvado Journal: Clin Chem Date: 2018-06-08 Impact factor: 8.327
Authors: Josune Olza; Concepción M Aguilera; Mercedes Gil-Campos; Rosaura Leis; Gloria Bueno; Miguel Valle; Ramón Cañete; Rafael Tojo; Luis A Moreno; Ángel Gil Journal: Ann Nutr Metab Date: 2015-01-21 Impact factor: 3.374
Authors: D Theofylaktopoulou; Ø Midttun; A Ulvik; P M Ueland; G S Tell; S E Vollset; O Nygård; S J P M Eussen Journal: Clin Exp Immunol Date: 2013-07 Impact factor: 4.330
Authors: Daniel Dylan Cohen; Diego Gómez-Arbeláez; Paul Anthony Camacho; Sandra Pinzon; Claudia Hormiga; Juanita Trejos-Suarez; John Duperly; Patricio Lopez-Jaramillo Journal: PLoS One Date: 2014-04-08 Impact factor: 3.240