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

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

doi:10.7717/peerj.11346

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

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

Authors

Yarong Yang^#¹, Zexin Huang^#¹, Zhao Yang¹, Ying Qi², Hui Shi¹, Yifei Zhou², Fangyu Wang¹, Miaofang Yang¹

Affiliations

¹ Department of Gastroenterology and Hepatology, Jinling Hospital, the First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu, China.
² Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.

^# Contributed equally.

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.

Keywords: Glycerophospholipids; Homocitrulline; Metabolic pathways; Metabolomics; Non-alcoholic fatty liver disease (NAFLD).

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81370546). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.