Liver Metabolomics Analysis Revealing Key Metabolites Associated with Different Stages of Nonalcoholic Fatty Liver Disease in Hamsters

Shan-Shan Gao; Yue-Liang Shen; Yun-Wen Chen; Xiu-Zhi Wei; Jing-Jing Hu; Jue Wang; Wen-Jing Wu

doi:10.2174/0113862073238503230924180432

Liver Metabolomics Analysis Revealing Key Metabolites Associated with Different Stages of Nonalcoholic Fatty Liver Disease in Hamsters

Comb Chem High Throughput Screen. 2023 Oct 5. doi: 10.2174/0113862073238503230924180432. Online ahead of print.

Authors

Shan-Shan Gao¹, Yue-Liang Shen², Yun-Wen Chen¹, Xiu-Zhi Wei¹, Jing-Jing Hu¹, Jue Wang¹, Wen-Jing Wu¹

Affiliations

¹ Department of Ultrasound, Ningbo Huamei Hospital, University of Chinese Academy of Sciences, Ningbo Zhejiang 315000, China.
² Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou Zhejiang 310011, China.

PMID: 37859316
DOI: 10.2174/0113862073238503230924180432

Abstract

Background and aim: Nonalcoholic fatty liver disease (NAFLD) is not only the top cause of liver diseases but also a hepatic-correlated metabolic syndrome. This study performed untargeted metabolomics analysis of NAFLD hamsters to identify the key metabolites to discriminate different stages of NAFLD.

Methods: Hamsters were fed a high-fat diet (HFD) to establish the NAFLD model with different stages (six weeks named as the NAFLD1 group and twelve weeks as the NAFLD2 group, respectively). Those liver samples were analyzed by untargeted metabolomics (UM) analysis to investigate metabolic changes and metabolites to discriminate different stages of NAFLD.

Results: The significant liver weight gain in NAFLD hamsters was observed, accompanied by significantly increased levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Moreover, the levels of TG, LDL-C, ALT, and AST were significantly higher in the NAFLD2 group than in the NAFLD1 group. The UM analysis also revealed the metabolic changes; 27 differently expressed metabolites were detected between the NAFLD2 and NAFLD1 groups. More importantly, the levels of N-methylalanine, allantoin, glucose, and glutamylvaline were found to be significantly different between any two groups (control, NAFLD2 and NAFLD1). Receiver operating characteristic curve (ROC) curve results also showed that these four metabolites are able to distinguish control, NAFLD1 and NAFLD2 groups.

Conclusion: This study indicated that the process of NAFLD in hamsters is accompanied by different metabolite changes, and these key differently expressed metabolites may be valuable diagnostic biomarkers and responses to therapeutic interventions.

Keywords: Nonalcoholic fatty liver disease; disease stage; high-fat diet; metabolites.; untargeted metabolomics.