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ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 1
Jan.  2023
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Article Navigation >  Journal of Clinical Hepatology  > 2023  >  39(1): 89-96

Role of glutathione transferase in nonalcoholic fatty liver disease: An analysis based on gene expression profile

DOI: 10.3969/j.issn.1001-5256.2023.01.014
  • 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

Research funding:

The Three-year Action Plan of Shanghai TCM Development (ZY-(2018-2020)-CCCX-5001);

Science and Technology Planning Project of Shanghai Science and Technology Commission (20Z21900100);

Shanghai Key Specialty of Traditional Chinese Clinical Medicine (shslczdzk01201)

More Information
  • Corresponding author: TAO yanyan, taoyanyan1023@126.com (ORCID: 0000-0002-8962-3137); LIU Chenghai, chenghailiu@hotmail.com (ORCID: 0000-0002-2033-0934)
  • Received Date: 2022-06-24
  • Accepted Date: 2022-09-27
  • Published Date: 2023-01-20
    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.

     

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