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血清代谢组学分析揭示中国非酒精性脂肪性肝病患者同型瓜氨酸水平升高:一项回顾性研究。

Serum metabolomic profiling reveals an increase in homocitrulline in Chinese patients with nonalcoholic fatty liver disease: a retrospective study.

作者信息

Yang Yarong, Huang Zexin, Yang Zhao, Qi Ying, Shi Hui, Zhou Yifei, Wang Fangyu, Yang Miaofang

机构信息

Department of Gastroenterology and Hepatology, Jinling Hospital, the First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu, China.

Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.

出版信息

PeerJ. 2021 May 3;9:e11346. doi: 10.7717/peerj.11346. eCollection 2021.

Abstract

BACKGROUNDS

Nonalcoholic fatty liver disease (NAFLD) has multiple causes, is triggered by individual genetic susceptibility, environmental factors, and metabolic disturbances, and may be triggered by acquired metabolic stress. The metabolic profiles of NAFLD show significant ethnic differences, and the metabolic characteristics of NAFLD in Chinese individuals are unclear. Our study aimed to identify the metabolites and pathways associated with NAFLD in a Chinese cohort.

METHODS

One hundred participants, including 50 NAFLD patients and 50 healthy controls, were enrolled in this retrospective observational study at Jinling Hospital in Nanjing; serum samples were collected from the patients and healthy subjects. The metabolome was determined in all samples by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). Univariate and multivariate statistical analyses were used to compare the metabolic profiles between the two groups.

RESULTS

The comparison indicated that the levels of 89 metabolites were different between the two groups. The glycerophospholipid family of metabolites was the most abundant family of metabolites that demonstrated significant differences. L-acetylcarnitine, L-homocitrulline, and glutamic acid were the top three metabolites ranked by VIP score and had favorable effective functions for diagnosis. Moreover, pathway enrichment analysis suggested 14 potentially different metabolic pathways between NAFLD patients and healthy controls based on their impact value. Biological modules involved in the lipid and carbohydrate metabolism had the highest relevance to the conditions of NAFLD. Glycerophospholipid metabolism had the strongest associations with the conditions of NAFLD.

CONCLUSIONS

Our data suggest that the serum metabolic profiles of NAFLD patients and healthy controls are different. L-Homocitrulline was remarkably increased in NAFLD patients.

摘要

背景

非酒精性脂肪性肝病(NAFLD)病因多样,由个体遗传易感性、环境因素和代谢紊乱引发,也可能由后天代谢应激触发。NAFLD的代谢谱存在显著的种族差异,中国人群中NAFLD的代谢特征尚不清楚。我们的研究旨在确定中国队列中与NAFLD相关的代谢物和代谢途径。

方法

本回顾性观察性研究在南京金陵医院招募了100名参与者,包括50名NAFLD患者和50名健康对照;收集患者和健康受试者的血清样本。通过液相色谱-混合四极杆飞行时间质谱(LC-Q/TOF-MS)测定所有样本的代谢组。采用单变量和多变量统计分析比较两组之间的代谢谱。

结果

比较表明两组之间89种代谢物的水平存在差异。代谢物中的甘油磷脂家族是显示出显著差异的最丰富的代谢物家族。L-乙酰肉碱、L-高瓜氨酸和谷氨酸是VIP评分排名前三的代谢物,对诊断具有良好的有效作用。此外,通路富集分析基于其影响值表明NAFLD患者和健康对照之间有14条潜在不同的代谢途径。参与脂质和碳水化合物代谢的生物模块与NAFLD的病情相关性最高。甘油磷脂代谢与NAFLD的病情关联最强。

结论

我们的数据表明NAFLD患者和健康对照的血清代谢谱不同。NAFLD患者中L-高瓜氨酸显著增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e718/8101472/ec3f40f68a44/peerj-09-11346-g001.jpg

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