Association of plasma kynurenine pathway metabolite concentrations with metabolic health risk in pre-pubertal Asian children
Association of plasma kynurenine pathway metabolite concentrations with metabolic health risk in pre-pubertal 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.
1128-1137
Tan, Karen Mei Ling
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Tint, Mya Thway
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Kothandaraman, Narasimhan
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Yap, Fabian
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Godfrey, Keith
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Lee, Yung Seng
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Tan, Kok Hian
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Gluckman, Peter D.
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Chong, Yap Seng
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Chong, Mary F.F.
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Eriksson, Johan G.
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Cameron-Smith, David
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June 2022
Tan, Karen Mei Ling
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Tint, Mya Thway
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Kothandaraman, Narasimhan
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Yap, Fabian
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Godfrey, Keith
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Lee, Yung Seng
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Tan, Kok Hian
4714c94d-334a-42ad-b879-f3aa3a931def
Gluckman, Peter D.
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Chong, Yap Seng
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Chong, Mary F.F.
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Eriksson, Johan G.
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Cameron-Smith, David
339e797d-5eeb-4fb2-888d-0fed1acde2f8
Tan, Karen Mei Ling, Tint, Mya Thway, Kothandaraman, Narasimhan, Yap, Fabian, Godfrey, Keith, Lee, Yung Seng, Tan, Kok Hian, Gluckman, Peter D., Chong, Yap Seng, Chong, Mary F.F., Eriksson, Johan G. and Cameron-Smith, David
(2022)
Association of plasma kynurenine pathway metabolite concentrations with metabolic health risk in pre-pubertal Asian children.
International Journal of Obesity, 46 (6), .
(doi: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.
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Accepted/In Press date: 28 January 2022
Published date: June 2022
Additional Information:
Funding Information:
The study is supported by the National Research Foundation (NRF) under the Open Fund-Large Collaborative Grant (OF-LCG; MOH-000504) administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC) and the Agency for Science, Technology and Research (A*STAR). In RIE2025, GUSTO is supported by funding from the NRF’s Human Health and Potential (HHP) Domain, under the Human Potential Programme
Funding Information:
YSC, PDG, and KMG are part of an academic consortium that has received research funding from companies selling nutritional products. KMG and DCS have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. KMG is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515-10042) and NIHR Southampton Biomedical Research Centre (IS-BRC-1215-20004)), the European Union (Erasmus+ Programme ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP) and the British Heart Foundation (RG/15/17/3174, SP/F/21/150013). All other authors declare no financial relationships with any organizations that might have an interest in the submitted work, and no other relationships or activities that could appear to have influenced the submitted work.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
Identifiers
Local EPrints ID: 454833
URI: http://eprints.soton.ac.uk/id/eprint/454833
ISSN: 0307-0565
PURE UUID: 105737f1-6545-4e42-846f-5d4e5b694088
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Date deposited: 24 Feb 2022 21:55
Last modified: 17 Mar 2024 07:05
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Contributors
Author:
Karen Mei Ling Tan
Author:
Mya Thway Tint
Author:
Narasimhan Kothandaraman
Author:
Fabian Yap
Author:
Yung Seng Lee
Author:
Kok Hian Tan
Author:
Peter D. Gluckman
Author:
Yap Seng Chong
Author:
Mary F.F. Chong
Author:
Johan G. Eriksson
Author:
David Cameron-Smith
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