Role of glutathione transferase in nonalcoholic fatty liver disease: An analysis based on gene expression profile
10.3969/j.issn.1001-5256.2023.01.014
- VernacularTitle:基因表达谱分析非酒精性脂肪性肝病中谷胱甘肽转移酶的作用
- Author:
Tingting SHEN
1
;
Gerui ZHU
1
;
Fan WANG
1
;
Xin SUN
2
;
Kai HUANG
2
;
Yuan PENG
1
;
Yanyan TAO
1
;
Chenghai LIU
1
,
2
Author Information
1. Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2. Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China
- Publication Type:Original Article_Fatty Liver Disease
- Keywords:
Non-alcoholic Fatty Liver Disease;
Glutathione Transferase;
Gene Expression Profiling
- From:
Journal of Clinical Hepatology
2023;39(1):89-96
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of glutathione transferase in nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet using the RNA-Seq technique in combination with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes. Methods A total of 14 male C57BL/6J mice were divided into control group with 6 mice and model group with 8 mice by random sampling. The mice in the control group were fed with normal diet, and those in the model group were fed with high-fat diet for 7 consecutive weeks to establish a model of NAFLD. Kits were used to measure the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the level of triglyceride (TG), and HE staining and oil red staining were used to observe liver pathology and deposition of lipid droplets. Liver tissue RNA was extracted for RNA-Seq, and genes with a fold change of ≥2.0 and a P value of < 0.05 were defined as differentially expressed genes; after differentially expressed genes were screened out between the control group and the model group, GO and KEGG enrichment analyses were performed, and qRT-PCR was used to validate the expression of the differentially expressed genes. The independent samples t -test was used for comparison of normally distributed continuous data between two groups. Results There were no significant differences between the two groups in body weight and the serum levels of ALT and AST (all P > 0.05). Compared with the control group, the model group had a significantly higher serum level of TG (2.02±0.50 mmol/L vs 1.00±0.29 mmol/L, t =-4.45, P =0.001). HE staining showed diffuse steatosis and ballooning degeneration in the model group, and oil red staining showed that the model group had a significant increase in orange-red lipid droplets in the cytoplasm of hepatocytes and a significantly higher grade of hepatocyte steatosis than the control group (1.88±0.64 vs 1.00±0.00, t =-3.86, P =0.006). RNA-seq results showed a total of 1367 differentially expressed genes between the two groups, among which there were 608 upregulated genes and 759 downregulated genes, and there were 17 differentially expressed GST genes between the two groups. The top 10 GST genes in terms of fold change were validated, and compared with the control group, the model group had downregulated expression of GSTa2, GSTa3, GSTa4, GSTm1, GSTm2, GSTm3, GSTm4, GSTp1, and GSTo1 and upregulated expression of GSTk1. The results of qRT-PCR were consistent with the results of sequencing. Conclusion GST affects lipid metabolism by participating in various biological processes such as steroid metabolism, fatty acid metabolism, and cholesterol metabolism and is closely associated with the pathogenesis of NAFLD.
