Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Department of Laboratory Medicine, National University Hospital, Singapore, Singapore.
Int J Obes (Lond). 2022 Jun;46(6):1128-1137. doi: 10.1038/s41366-022-01085-4. Epub 2022 Feb 16.
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.
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.
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).
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.
色氨酸-犬尿氨酸（KYN）途径与肥胖相关的全身炎症和代谢健康有关。该途径产生多种代谢物，但关于它们与儿童早期代谢疾病风险增加的标志物之间的关系，几乎没有可用的数据。本研究的目的是探讨 KYN 途径代谢物与亚洲 8 岁儿童代谢风险标志物的关系。
采用液相色谱-串联质谱法检测 552 名来自新加坡成长至健康结局（GUSTO）前瞻性母婴队列研究的 8 岁儿童的 KYN 途径代谢物的空腹血浆浓度。利用当地的 BMI 年龄百分位图，根据儿童的体重和身高确定超重和肥胖。使用定量磁共振测量体脂肪百分比。通过计算稳态模型评估胰岛素抵抗（HOMA-IR）、甘油三酯和高密度脂蛋白胆固醇，评估代谢综合征评分（MetS）。使用血清甘油三酯、BMI、γ-谷氨酰转移酶（GGT）和腹围计算脂肪肝指数（FLI）。使用多元回归分析来检验相关性。
在超重或肥胖的儿童（n=93；队列的 16.9%）中，与体重正常的儿童相比，所有 KYN 途径代谢物均显著升高。KYN、犬尿氨酸（KA）、黄尿酸（XA）、羟基犬尿氨酸（HAA）和喹啉酸（QA）与体脂肪百分比（QA 的 B（95%CI）=0.32（0.22,0.42））、HOMA-IR（QA 的 B（95%CI）=0.25（0.16,0.34））和收缩压（QA 的 B（95%CI）=0.14（0.06,0.22））均呈显著正相关。除 3-羟基犬尿氨酸（HK）外，所有 KYN 代谢物均与代谢综合征（QA 的 B（95%CI）=0.29（0.21,0.37））和脂肪肝（QA 的 B（95%CI）=0.30（0.21,0.39））显著相关。
在亚洲 8 岁儿童中，较高的 KYN 途径代谢物血浆浓度与肥胖以及代谢综合征和脂肪肝的风险增加有关。
