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

Heng ZHU; Weizong KONG; Guiqun HUANG; Yu BAI; Yingchun WANG

doi:10.3969/j.issn.1001-5256.2022.09.013

Volume 38 Issue 9

Sep. 2022

Turn off MathJax

Article Contents

Abstract

References

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

PDF( 2418 KB)

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

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.
- Non-Alcoholic Fatty Liver Disease,
- Histone Deacetylase 1,
- Insulin Resistance

FullText(HTML)

References(14)

References

[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.

Relative Articles

[1]	Qingxia LIU, Chenggang ZHANG, Haolin TANG, Wenjing QU, Huifan JI, Xiaolin GUO. A case of primary biliary cholangitis with connective tissue disease and immune thrombocytopenia[J]. Journal of Clinical Hepatology, 2023, 39(6): 1404-1407. doi: 10.3969/j.issn.1001-5256.2023.06.022
[2]	Haifeng LIU, Simin ZHOU, Jiwen LI, Jiangpeng LIU, Bangmao WANG, Lu ZHOU. Effect of depression on response to ursodeoxycholic acid and the occurrence of liver cirrhosis in patients with primary biliary cholangitis[J]. Journal of Clinical Hepatology, 2023, 39(12): 2817-2823. doi: 10.3969/j.issn.1001-5256.2023.12.011
[3]	Mei CHEN, Ning MA, Jingbo JIN, Yu PENG, Sitong FAN, Fang WANG. A case of primary biliary cholangitis with megaloblastic anemia[J]. Journal of Clinical Hepatology, 2022, 38(5): 1114-1115. doi: 10.3969/j.issn.1001-5256.2022.05.026
[4]	Xing LYU, Ting LI, Xiaodong SUN, Jianpeng ZHOU, Dongxia WANG, Guoyue LYU. Research advances in the treatment of primary biliary cirrhosis[J]. Journal of Clinical Hepatology, 2022, 38(9): 2130-2135. doi: 10.3969/j.issn.1001-5256.2022.09.035
[5]	Fang QIU, Chan WANG, Mingming ZHANG, Xingjuan SHI, Xiangdong LIU. Genetic studies of primary biliary cholangitis in the post-GWAS era[J]. Journal of Clinical Hepatology, 2022, 38(4): 759-761. doi: 10.3969/j.issn.1001-5256.2022.04.005
[6]	Haitao MA, Yingmei TANG. Research advances in exosomes in primary biliary cholangitis[J]. Journal of Clinical Hepatology, 2022, 38(8): 1896-1900. doi: 10.3969/j.issn.1001-5256.2022.08.035
[7]	Chinese Society of Hepatology. Guidelines on the diagnosis and management of primary biliary cholangitis (2021)[J]. Journal of Clinical Hepatology, 2022, 38(1): 35-41. doi: 10.3760/cma.j.cn112138-20211112-00794
[8]	Xi CHU, Lianjun XING. Role of anion exchanger 2 in the pathogenesis of primary biliary cholangitis[J]. Journal of Clinical Hepatology, 2021, 37(3): 718-720. doi: 10.3969/j.issn.1001-5256.2021.03.044
[9]	Yafei YANG, Zhihua DENG. Immune mechanism of biliary epithelial cell injury in the small intrahepatic bile ducts in primary biliary cholangitis[J]. Journal of Clinical Hepatology, 2021, 37(6): 1466-1468. doi: 10.3969/j.issn.1001-5256.2021.06.051
[10]	Jia Gui, Shang YuLong, Han Ying. An investigation of quality of life and treatment of patients with primary biliary cholangitis[J]. Journal of Clinical Hepatology, 2020, 36(9): 2021-2024. doi: 10.3969/j.issn.1001-5256.2020.09.022
[11]	Wang XiaoJing, Liu Yao, Wang XianBo. Biochemical response and integrated traditional Chinese and Western medicine therapy for primary biliary cholangitis[J]. Journal of Clinical Hepatology, 2020, 36(1): 26-30. doi: 10.3969/j.issn.1001-5256.2020.01.004
[12]	Ma WeiYu, Deng ZhiHua. Current status of immunogenetic studies on primary biliary cholangitis[J]. Journal of Clinical Hepatology, 2020, 36(4): 932-935. doi: 10.3969/j.issn.1001-5256.2020.04.050
[13]	Wei Jing, Wu XiRun. Current status of research on fibrates in treatment of primary biliary cholangitis[J]. Journal of Clinical Hepatology, 2020, 36(2): 442-445. doi: 10.3969/j.issn.1001-5256.2020.02.046
[14]	Tu RongFang, Yang Xue, Tang YingMei. Research advances in primary biliary cholangitis with extrahepatic autoimmune diseases[J]. Journal of Clinical Hepatology, 2020, 36(6): 1398-1401. doi: 10.3969/j.issn.1001-5256.2020.06.046
[15]	Yang Ning, Liu YanSheng, Han Ying. Diagnosis and treatment of primary biliary cholangitis-autoimmune hepatitis overlap syndrome[J]. Journal of Clinical Hepatology, 2020, 36(3): 697-700. doi: 10.3969/j.issn.1001-5256.2020.03.051
[16]	Shu YanYun, Pan XiaoLi, Song YuHu, Ye Jin. Clinical features of autoimmune hepatitis and primary biliary cholangitis: A comparative analysis[J]. Journal of Clinical Hepatology, 2019, 35(2): 354-358. doi: 10.3969/j.issn.1001-5256.2019.02.022
[17]	Wang Jing, Zhang BiQing, Pan YunZhi, Zhu ChuanWu. Role of microRNA in the pathogenesis, diagnosis, and outcome evaluation of primary biliary cholangitis[J]. Journal of Clinical Hepatology, 2019, 35(7): 1636-1639. doi: 10.3969/j.issn.1001-5256.2019.07.047
[18]	Yang QianQian, Ren TianQi, Xue ShuWen, Chen QingLing, Feng LiNa, Zhang XiaoXue, Wen XiaoYu, Jin QingLong. Primary biliary cholangitis with myelofibrosis: A case report[J]. Journal of Clinical Hepatology, 2019, 35(9): 2057-2058. doi: 10.3969/j.issn.1001-5256.2019.09.036
[19]	Wang Jing, Zhao LiLi, Shi RuiFang, Liu YongGang, Li Jia. Early treatment of PBC-AIH overlap syndrome with histological remission: A case report[J]. Journal of Clinical Hepatology, 2019, 35(9): 2059-2061. doi: 10.3969/j.issn.1001-5256.2019.09.037
[20]	Li ShuXiang, Duan WeiJia, Zhang Dong, You Hong, Jia JiDong. Research advances in autoimmune hepatitis and primary biliary cholangitis in 2017[J]. Journal of Clinical Hepatology, 2018, 34(7): 1569-1572. doi: 10.3969/j.issn.1001-5256.2018.07.044

Supplements(0)

Cited By

Cited by

Periodical cited type(5)

1.	王耀磊，王盼攀. 肝门部胆管癌患者术后并发症发生情况及其影响因素的Logistic回归分析. 医学理论与实践. 2024(11): 1822-1825 .
2.	李明，于群，肖熙，刘影倩，黄裕存. 外科Apgar评分及POSSUM评分对老年严重胸部外伤术后预后的评估价值. 名医. 2023(09): 30-32 .
3.	朱磊，赵海淳，李珊珊，孟君. 外科Apgar评分对术前新辅助化疗进展期胃癌术后并发症的预测价值. 中国现代普通外科进展. 2022(12): 990-993 .
4.	章周海，涂从银. 肝门部胆管癌的手术疗效分析. 肝胆外科杂志. 2021(03): 223-225 .
5.	遆军锋，温陈，张小云，姜丹丹. 肝门部胆管癌术后并发症发生危险因素及术前外科改良 Apgar评分、血清总胆红素水平对并发症的预测价值. 陕西医学杂志. 2021(12): 1513-1516 .

Other cited types(0)

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(3) / Tables(7)

Get Citation

PDF

XML

Article Metrics

Article views (609) PDF downloads(43)

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