Dynamic pattern of postprandial bile acids in paediatric non-alcoholic fatty liver disease

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver International Pub Date : 2024-07-31 DOI:10.1111/liv.16054

Jiating Huang, Hu Lin, A-Na Liu, Wei Wu, Anna Alisi, Rohit Loomba, Cuifang Xu, Wenqin Xiang, Jie Shao, Guanping Dong, Ming-Hua Zheng, Junfen Fu, Yan Ni

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Abstract

Background

Dysregulation of bile acids (BAs), as important signalling molecules in regulating lipid and glucose metabolism, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, static BA profiles during fasting may obscure certain pathogenetic aspects. In this study, we investigate the dynamic alterations of BAs in response to an oral glucose tolerance test (OGTT) among children with NAFLD.

Methods

We recruited 230 subjects, including children with overweight/obesity, or complicated with NAFLD, and healthy controls. Serum BAs, 7-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) were quantified during OGTT. Clinical markers related to liver function, lipid metabolism and glucose metabolism were assessed at baseline or during OGTT.

Findings

Conjugated BAs increased while unconjugated ones decreased after glucose uptake. Most BAs were blunted in response to glucose in NAFLD (p > .05); only glycine and taurine-conjugated chenodeoxycholic acid (CDCA) and cholic acid (CA) were responsive (p < .05). Primary BAs were significantly increased while secondary BAs were decreased in NAFLD. C4 and FGF19 were significantly increased while their ratio FGF19/C4 ratio was decreased in NAFLD. The dynamic pattern of CDCA and taurine-conjugated hyocholic acid (THCA) species was closely correlated with glucose (correlation coefficient r = .175 and −.233, p < .05), insulin (r = .327 and −.236, p < .05) and c-peptide (r = .318 and −.238, p < .05). Among which, CDCA was positively associated with liver fat content in NAFLD (r = .438, p < .05). Additionally, glycochenodeoxycholic acid (GCDCA), CDCA and THCA were potential biomarkers to discriminate paediatric NAFLD from healthy controls and children with obesity.

Interpretation

This study provides novel insights into the dynamics of BAs during OGTT in paediatric NAFLD. The observed variations in CDCA and HCA species were associated with liver dysfunction, dyslipidaemia and dysglycaemia, highlighting their potential roles as promising diagnostic and therapeutic targets in NAFLD.

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儿科非酒精性脂肪肝患者餐后胆汁酸的动态模式。

背景：胆汁酸（BA）是调节脂质和葡萄糖代谢的重要信号分子，胆汁酸失调会导致非酒精性脂肪肝（NAFLD）的发生。然而，空腹时的静态胆汁酸曲线可能会掩盖某些致病方面。在这项研究中，我们调查了非酒精性脂肪肝患儿在进行口服葡萄糖耐量试验（OGTT）时 BA 的动态变化：方法：我们招募了 230 名受试者，包括超重/肥胖或并发非酒精性脂肪肝的儿童以及健康对照组。在 OGTT 期间对血清 BA、7-羟基-4-胆甾烯-3-酮（C4）和成纤维细胞生长因子 19（FGF19）进行量化。在基线或 OGTT 期间评估了与肝功能、脂代谢和糖代谢有关的临床指标：结果：葡萄糖摄入后，结合型 BAs 增加，而非结合型 BAs 减少。在非酒精性脂肪肝患者中，大多数 BA 对葡萄糖的反应减弱（p > .05）；只有甘氨酸和牛磺酸共轭的去氧胆酸（CDCA）和胆酸（CA）有反应（p 解释：该研究为了解非酒精性脂肪肝患者肝脏对葡萄糖的反应提供了新的视角：本研究为了解小儿非酒精性脂肪肝患者在 OGTT 期间 BA 的动态变化提供了新的视角。观察到的 CDCA 和 HCA 种类的变化与肝功能异常、血脂异常和血糖异常有关，突出了它们作为非酒精性脂肪肝诊断和治疗靶点的潜在作用。

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

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.