Tryptophan derivatives as non-invasive diagnostic indicators for obesity-related MASLD in children and adolescents.

IF 5.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes, Obesity & Metabolism Pub Date : 2025-10-01 DOI:10.1111/dom.70162

Shumin Zhan, Xingyun Wang, Chen Wang, Bowen Zhu, Jianfang Gao, Zhou Peng, Rui Wang, Yun Yang, Liang Zhang, Tengfei Wang, Jiaoxiang Wu, Wei Wu, Ke Huang, Guanping Dong, Qiannan Ren, Shan Wang, Senjie Wang, Xuelian Zhou, Liling Xu, Junfen Fu, Xirong Guo

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引用次数: 0

Abstract

Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major health burden in children and adolescents with obesity. This study aimed to characterize metabolic alterations associated with obesity-related MASLD and to evaluate the potential of tryptophan (TRP)-derived metabolites as non-invasive biomarkers for early diagnosis.

Materials and methods: A total of 30 normal-weight individuals and 80 patients diagnosed with obesity were included in the discovery cohort. Circulating metabolites were quantified and compared among normal-weight individuals, patients with obesity, and those with obesity-related MASLD to identify metabolic changes associated with disease status. In vitro experiments using mouse hepatocytes and liver organoids were conducted to assess the effects of TRP-derived metabolites on intracellular lipid accumulation. Finally, a non-invasive diagnostic model was developed using machine learning techniques and validated in an independent cohort of 112 individuals.

Results: Circulating TRP metabolism was markedly elevated in children and adolescents with obesity-related MASLD compared with both normal-weight controls and individuals with simple obesity. TRP-derived metabolites significantly promoted intracellular lipid accumulation in mouse hepatocytes and liver organoids via the induction of oxidative stress. The non-invasive diagnostic model based on TRP-derived metabolites demonstrated robust performance in differentiating obesity-related MASLD from simple obesity in both the discovery and validation cohorts.

Discussion: These findings highlight the pivotal role of TRP metabolism in the pathogenesis of MASLD in children and adolescents with obesity. Elevated TRP-derived metabolites may contribute to hepatic lipid accumulation through oxidative stress and serve as promising non-invasive biomarkers for the early diagnosis of obesity-related MASLD. The machine learning-based diagnostic model offers a practical and less invasive alternative to current diagnostic approaches such as liver biopsy.

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色氨酸衍生物作为儿童和青少年肥胖相关MASLD的无创诊断指标

目的：代谢功能障碍相关的脂肪变性肝病（MASLD）是儿童和青少年肥胖的主要健康负担。本研究旨在表征与肥胖相关的MASLD相关的代谢改变，并评估色氨酸（TRP）衍生代谢物作为早期诊断的非侵入性生物标志物的潜力。材料与方法：发现队列共纳入30名正常体重个体和80名诊断为肥胖的患者。对正常体重个体、肥胖患者和肥胖相关MASLD患者的循环代谢物进行量化和比较，以确定与疾病状态相关的代谢变化。利用小鼠肝细胞和肝类器官进行体外实验，以评估trp衍生代谢物对细胞内脂质积累的影响。最后，利用机器学习技术开发了一种非侵入性诊断模型，并在112名个体的独立队列中进行了验证。结果：与正常体重对照组和单纯性肥胖患者相比，肥胖相关MASLD儿童和青少年的循环TRP代谢明显升高。trp衍生代谢物通过诱导氧化应激显著促进小鼠肝细胞和肝类器官细胞内脂质积累。在发现和验证队列中，基于trp衍生代谢物的无创诊断模型在区分肥胖相关MASLD和单纯性肥胖方面表现出色。讨论：这些发现强调了TRP代谢在儿童和青少年肥胖MASLD发病机制中的关键作用。升高的trp衍生代谢物可能通过氧化应激促进肝脏脂质积累，并可作为早期诊断肥胖相关MASLD的有前途的非侵入性生物标志物。基于机器学习的诊断模型为当前的诊断方法（如肝活检）提供了一种实用且侵入性较小的替代方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.