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Volume 38 Issue 9
Sep.  2022
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Article Navigation >  Journal of Clinical Hepatology  > 2022  >  38(9): 2010-2015

Influence of histone deacetylase 1 on insulin resistance in a cell model of nonalcoholic fatty liver disease

DOI: 10.3969/j.issn.1001-5256.2022.09.013
  • 1.

    Second Department of Gastroenterology, Zhongshan Hospital Affiliated to Dalian University, Dalian, Liaoning 116001, China

  • 2.

    Dalian University, Dalian, Liaoning 116001, China

Research funding:

Special Fund for Doctoral Startup of Dalian University (20181QL005)

More Information
  • Corresponding author: WANG Yingchun, wych_1648@126.com(ORCID: 0000-0002-6664-4947)
  • Received Date: 2022-01-15
  • Accepted Date: 2022-02-24
  • Published Date: 2022-09-20
    Abstract
  •   Objective  To investigate the promoting effect of histone deacetylase 1 (HDAC1) expression on insulin resistance (IR) in nonalcoholic fatty liver disease (NAFLD) cells by establishing an HepG2 cell model of high fat-induced NAFLD.  Methods  HepG2 cells were divided into control group, model group (OA), and inhibitor group (OA+pyroxamide [an HDAC1 inhibitor]). CCK-8 assay was used to plot the standard growth curve of HepG2 cells and screen out the optimal drug concentration and action time of OA and pyroxamide; oil red O staining was used to compare the accumulation of lipid droplets in cells; an automatic biochemical analyzer was used to analyze the content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and total cholesterol (TC) in cells; quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of HDAC1 and insulin receptor substrate-1 (IRS-1) in cells. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups.  Results  OA treatment at a concentration of 0.25 mmol/L for 24 hours was the optimal concentration and duration of cell modeling, and treatment at a concentration of 20 μmol/L for 24 hours was the optimal administration concentration and duration of pyroxamide. Compared with the control group, the model group had significant increases in the content of ALT, AST, TG, and TC, and compared with the model group, the inhibitor group had significant reductions in the content of ALT, AST, TG, and TC (all P < 0.05). The model group had significantly higher mRNA and protein expression levels of HDAC1 than the control group, while the inhibitor group had significantly lower expression levels than the model group (all P < 0.05); the model group had significantly lower mRNA and protein expression levels of IRS-1 than the control group, while the inhibitor group had significantly higher expression levels than the model group (all P < 0.05).  Conclusion  HDAC1 participates in the development and progression of NAFLD by inhibiting the expression of IRS-1 molecule and promoting IR, and the HDAC1 inhibitor pyroxamide can exert a protective effect on the liver by alleviating IR.

     

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    • References(14)
  • [1]
    National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association; Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease: A 2018 update[J]. J Clin Hepatol, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007.

    中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007.
    [2]
    WANG YH, GAO Y. Research progress in diagnosis and treatment of non-alcoholic fatty liver disease combinated with type 2 diabetes mellitus[J]. J Jilin Univ(Med Edit), 2020, 286(6): 1324-1331. DOI: 10.13481/j.1671-587x.20200634.

    王雨涵, 高影. 非酒精性脂肪性肝病并发2型糖尿病诊断和治疗的研究进展[J]. 吉林大学学报(医学版), 2020, 286(6): 1324-1331. DOI: 10.13481/j.1671-587x.20200634.
    [3]
    DAY CP, JAMES OF. Steatohepatitis: a tale of two "hits"?[J]. Gastroenterology, 1998, 114(4): 842-845. DOI: 10.1016/s0016-5085(98)70599-2.
    [4]
    YANG ZB, PENG H, MA SW. Progress in epigenetics of liver diseases[J]. Chin Hepatol, 2017, 22(5): 381-384. DOI: 10.3969/j.issn.1008-1704.2017.05.002.

    杨智彬, 彭惠, 马世武. 肝脏疾病的表观遗传学研究进展[J]. 肝脏, 2017, 22(5): 381-384. DOI: 10.3969/j.issn.1008-1704.2017.05.002.
    [5]
    CASTELLANO D, RAMOS B, OLIVA W, et al. Genome profiling of H3k4me3 histone modification in human adipose tissue during obesity and insulin resistance[J]. Biomedicines, 2021, 9(10): 1363. DOI: 10.3390/biomedicines9101363.
    [6]
    FU S, YU M, TAN Y, et al. Role of histone deacetylase on nonalcoholic fatty liver disease[J]. Expert Rev Gastroenterol Hepatol, 2021, 15(4): 353-361. DOI: 10.1080/17474124.2021.1854089.
    [7]
    SODUM N, KUMAR G, BOJJA SL, et al. Epigenetics in NAFLD/NASH: Targets and therapy[J]. Pharmacol Res, 2021, 167: 105484. DOI: 10.1016/j.phrs.2021.105484.
    [8]
    GUO YW, TAO L, LIN XY, et al. Role of histone deacetylase 1 in course of mice NAFLD[J]. J Sun Yat-Sen Univ(Medical Sciences), 2016, 37(6): 840-844. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSYK201606008.htm

    郭云蔚, 陶力, 林显艺, 等. 组蛋白去乙酰化酶1在小鼠非酒精性脂肪肝中的表达和作用[J]. 中山大学学报(医学科学版), 2016, 37(6): 840-844. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSYK201606008.htm
    [9]
    RAJAN PK, UDOH UA, SANABRIA JD, et al. The role of histone acetylation-/methylation-mediated apoptotic gene regulation in hepatocellular carcinoma[J]. Int J Mol Sci, 2020, 21(23): 8894. DOI: 10.3390/ijms21238894.
    [10]
    JAMES DE, STÖCKLI J, BIRNBAUM MJ. The aetiology and molecular landscape of insulin resistance[J]. Nat Rev Mol Cell Biol, 2021, 22(11): 751-771. DOI: 10.1038/s41580-021-00390-6.
    [11]
    YANG Q, VIJAYAKUMAR A, KAHN BB. Metabolites as regulators of insulin sensitivity and metabolism[J]. Nat Rev Mol Cell Biol, 2018, 19(10): 654-672. DOI: 10.1038/s41580-018-0044-8.
    [12]
    MAUDE H, SANCHEZ-CABANILLAS C, CEBOLA I. Epigenetics of hepatic insulin resistance[J]. Front Endocrinol (Lausanne), 2021, 12: 681356. DOI: 10.3389/fendo.2021.681356.
    [13]
    KHAN S, KOMARYA SK, JENA G. Phenylbutyrate and β-cell function: contribution of histone deacetylases and ER stress inhibition[J]. Epigenomics, 2017, 9(5): 711-720. DOI: 10.2217/epi-2016-0160.
    [14]
    KHAN S, KUMAR S, JENA G. Valproic acid reduces insulin-resistance, fat deposition and FOXO1-mediated gluconeogenesis in type-2 diabetic rat[J]. Biochimie, 2016, 125: 42-52. DOI: 10.1016/j.biochi.2016.02.014.
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