- 中国精品科技期刊
- 中国高校百佳科技期刊
- 中国中文核心期刊
- 中国科学引文数据库核心期刊
| Citation: |
YAN Li, JU Fengyu, SHEN Xin, et al. Research progress of acetylation in the pathogenesis of MASLD[J]. J China Pharm Univ, 2025, 56(1): 31 − 39. DOI: 10.11665/j.issn.1000-5048.2024030103
|
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent cause of chronic liver disease worldwide, and its intricate pathogenesis presents challenges in the development of new drugs. As a common way of post-translational modification, acetylation regulates protein stability, enzyme activity, and subcellular localization, occurring extensively in MASLD-associated processes such as lipid metabolism, inflammatory response, and oxidative stress. In this paper, we comprehensively review the mechanism of acetylation in MASLD, analyze the expression levels of acetylases in liver tissues of MASLD patients from the gene expression omnibus (GEO), discuss the changes in relevant enzyme expression and mechanisms in animal models, and further explore the feasibility of targeting acetylation for MASLD treatment, in the hope of offering a new perspective for advancing drug discovery in the field of MASLD.
| [1] |
Byrne CD, Targher G. NAFLD: a multisystem disease[J]. J Hepatol, 2015, 62 (1 Suppl): S47-S64.
|
| [2] |
Eslam M, Sanyal AJ, George J, et al. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease[J]. Gastroenterology, 2020, 158(7): 1999-2014. doi: 10.1053/j.gastro.2019.11.312
|
| [3] |
Devarbhavi H, Asrani SK, Arab JP, et al. Global burden of liver disease: 2023 update[J]. J Hepatol, 2023, 79(2): 516-537. doi: 10.1016/j.jhep.2023.03.017
|
| [4] |
Du T, Chen J, Shen X. Research advances in susceptibility genes of non-alcoholic fatty liver disease and its association with type 2 diabetes[J]. J China Pharm Univ (中国药科大学学报), 2018, 49(5): 537-544.
|
| [5] |
Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(1): 11-20. doi: 10.1038/nrgastro.2017.109
|
| [6] |
Ipsen DH, Lykkesfeldt J, Tveden-Nyborg P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease[J]. Cell Mol Life Sci, 2018, 75(18): 3313-3327. doi: 10.1007/s00018-018-2860-6
|
| [7] |
Chen Z, Tian RF, She ZG, et al. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease[J]. Free Radic Biol Med, 2020, 152: 116-141. doi: 10.1016/j.freeradbiomed.2020.02.025
|
| [8] |
Machado MV, Diehl AM. Pathogenesis of nonalcoholic steatohepatitis[J]. Gastroenterology, 2016, 150(8): 1769-1777. doi: 10.1053/j.gastro.2016.02.066
|
| [9] |
Nassir F. NAFLD: mechanisms, treatments, and biomarkers[J]. Biomolecules, 2022, 12(6): 824. doi: 10.3390/biom12060824
|
| [10] |
Masoodi M, Gastaldelli A, Hyötyläinen T, et al. Metabolomics and lipidomics in NAFLD: biomarkers and non-invasive diagnostic tests[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(12): 835-856. doi: 10.1038/s41575-021-00502-9
|
| [11] |
Bohinc BN, Michelotti G, Xie GH, et al. Repair-related activation of hedgehog signaling in stromal cells promotes intrahepatic hypothyroidism[J]. Endocrinology, 2014, 155(11): 4591-4601. doi: 10.1210/en.2014-1302
|
| [12] |
Harrison SA, Bedossa P, Guy CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis[J]. N Engl J Med, 2024, 390(6): 497-509. doi: 10.1056/NEJMoa2309000
|
| [13] |
Zeng J, Fan JG, Francque SM. Therapeutic management of metabolic dysfunction associated steatotic liver disease[J]. United European Gastroenterol J, 2024, 12(2): 177-186. doi: 10.1002/ueg2.12525
|
| [14] |
Rotman Y, Sanyal AJ. Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease[J]. Gut, 2017, 66(1): 180-190. doi: 10.1136/gutjnl-2016-312431
|
| [15] |
Zhao SS, Zhang L, Zhao JZ, et al. Characteristics of contemporary drug clinical trials regarding the treatment of non-alcoholic steatohepatitis[J]. Diabetes MeTable Syndr, 2024, 18(1): 102921. doi: 10.1016/j.dsx.2023.102921
|
| [16] |
Shvedunova M, Akhtar A. Modulation of cellular processes by histone and non-histone protein acetylation[J]. Nat Rev Mol Cell Biol, 2022, 23(5): 329-349. doi: 10.1038/s41580-021-00441-y
|
| [17] |
Drazic A, Myklebust LM, Ree R, et al. The world of protein acetylation[J]. Biochim Biophys Acta, 2016, 1864(10): 1372-1401. doi: 10.1016/j.bbapap.2016.06.007
|
| [18] |
Whedon SD, Cole PA. KATs off: Biomedical insights from lysine acetyltransferase inhibitors[J]. Curr Opin Chem Biol, 2023, 72: 102255. doi: 10.1016/j.cbpa.2022.102255
|
| [19] |
Seto E, Yoshida M. Erasers of histone acetylation: the histone deacetylase enzymes[J]. Cold Spring Harb Perspect Biol, 2014, 6(4): a018713. doi: 10.1101/cshperspect.a018713
|
| [20] |
Yang S, Hwang S, Kim B, et al. Fatty acid oxidation facilitates DNA double-strand break repair by promoting PARP1 acetylation[J]. Cell Death Dis, 2023, 14(7): 435. doi: 10.1038/s41419-023-05968-w
|
| [21] |
Park JM, Jo SH, Kim MY, et al. Role of transcription factor acetylation in the regulation of metabolic homeostasis[J]. Protein Cell, 2015, 6(11): 804-813. doi: 10.1007/s13238-015-0204-y
|
| [22] |
Liu DX, Qian DM, Wang B, et al. p300-Dependent ATF5 acetylation is essential for Egr-1 gene activation and cell proliferation and survival[J]. Mol Cell Biol, 2011, 31(18): 3906-3916. doi: 10.1128/MCB.05887-11
|
| [23] |
Wang W, Zheng YX, Sun SH, et al. A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence[J]. Sci Transl Med, 2021, 13(575): eabd2655. doi: 10.1126/scitranslmed.abd2655
|
| [24] |
Zhang SC, Xu PY, Zhu ZW, et al. Acetylation of p65Lys310 by p300 in macrophages mediates anti-inflammatory property of berberine[J]. Redox Biol, 2023, 62: 102704. doi: 10.1016/j.redox.2023.102704
|
| [25] |
Chi ZX, Chen S, Xu T, et al. Histone deacetylase 3 couples mitochondria to drive IL-1β-dependent inflammation by configuring fatty acid oxidation[J]. Mol Cell, 2020, 80(1): 43-58. e7.
|
| [26] |
Bricambert J, Miranda J, Benhamed F, et al. Salt-inducible kinase 2 links transcriptional coactivator p300 phosphorylation to the prevention of ChREBP-dependent hepatic steatosis in mice[J]. J Clin Invest, 2010, 120(12): 4316-4331. doi: 10.1172/JCI41624
|
| [27] |
Hou TY, Tian Y, Cao ZY, et al. Cytoplasmic SIRT6-mediated ACSL5 deacetylation impedes nonalcoholic fatty liver disease by facilitating hepatic fatty acid oxidation[J]. Mol Cell, 2022, 82(21): 4099-4115. e9.
|
| [28] |
Wei YD, Tian C, Zhao YX, et al. MRG15 orchestrates rhythmic epigenomic remodelling and controls hepatic lipid metabolism[J]. Nat Metab, 2020, 2(5): 447-460. doi: 10.1038/s42255-020-0203-z
|
| [29] |
Tian C, Min XW, Zhao YX, et al. MRG15 aggravates non-alcoholic steatohepatitis progression by regulating the mitochondrial proteolytic degradation of TUFM[J]. J Hepatol, 2022, 77(6): 1491-1503. doi: 10.1016/j.jhep.2022.07.017
|
| [30] |
Lin RT, Tao R, Gao X, et al. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth[J]. Mol Cell, 2013, 51(4): 506-518. doi: 10.1016/j.molcel.2013.07.002
|
| [31] |
Guo L, Guo YY, Li BY, et al. Enhanced acetylation of ATP-citrate lyase promotes the progression of nonalcoholic fatty liver disease[J]. J Biol Chem, 2019, 294(31): 11805-11816. doi: 10.1074/jbc.RA119.008708
|
| [32] |
Li XZ, Ding KX, Li XY, et al. Deficiency of WTAP in hepatocytes induces lipoatrophy and non-alcoholic steatohepatitis (NASH)[J]. Nat Commun, 2022, 13(1): 4549. doi: 10.1038/s41467-022-32163-w
|
| [33] |
Mikula M, Majewska A, Ledwon JK, et al. Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver[J]. Int J Mol Med, 2014, 34(6): 1647-1654. doi: 10.3892/ijmm.2014.1958
|
| [34] |
Ozden O, Park SH, Kim HS, et al. Acetylation of MnSOD directs enzymatic activity responding to cellular nutrient status or oxidative stress[J]. Aging, 2011, 3(2): 102-107. doi: 10.18632/aging.100291
|
| [35] |
Zhang JL, Zhao YJ, Wang SH, et al. CREBH alleviates mitochondrial oxidative stress through SIRT3 mediating deacetylation of MnSOD and suppression of Nlrp3 inflammasome in NASH[J]. Free Radic Biol Med, 2022, 190: 28-41. doi: 10.1016/j.freeradbiomed.2022.07.018
|
| [36] |
Yang XD, Chen Z, Ye L, et al. Esculin protects against methionine choline-deficient diet-induced non-alcoholic steatohepatitis by regulating the Sirt1/NF-κB p65 pathway[J]. Pharm Biol, 2021, 59(1): 922-932.
|
| [37] |
Sarkar A, Mitra P, Lahiri A, et al. Butyrate limits inflammatory macrophage niche in NASH[J]. Cell Death Dis, 2023, 14(5): 332. doi: 10.1038/s41419-023-05853-6
|
| [38] |
Ha TS, Shin TG, Jo IJ, et al. Lactate clearance and mortality in septic patients with hepatic dysfunction[J]. Am J Emerg Med, 2016, 34(6): 1011-1015. doi: 10.1016/j.ajem.2016.02.053
|
| [39] |
Wang TX, Chen K, Yao WL, et al. Acetylation of lactate dehydrogenase B drives NAFLD progression by impairing lactate clearance[J]. J Hepatol, 2021, 74(5): 1038-1052. doi: 10.1016/j.jhep.2020.11.028
|
| [40] |
Zhang LQ, Zhang ZG, Li CB, et al. S100A11 promotes liver steatosis via FOXO1-mediated autophagy and lipogenesis[J]. Cell Mol Gastroenterol Hepatol, 2021, 11(3): 697-724. doi: 10.1016/j.jcmgh.2020.10.006
|
| [41] |
Ren HH, Hu FQ, Wang D, et al. Sirtuin 2 prevents liver steatosis and metabolic disorders by deacetylation of hepatocyte nuclear factor 4α[J]. Hepatology, 2021, 74(2): 723-740. doi: 10.1002/hep.31773
|
| [42] |
Chen MT, Hui SC, Lang HD, et al. SIRT3 deficiency promotes high-fat diet-induced nonalcoholic fatty liver disease in correlation with impaired intestinal permeability through gut microbial dysbiosis[J]. Mol Nutr Food Res, 2019, 63(4): e1800612. doi: 10.1002/mnfr.201800612
|
| [43] |
Li Z, Zhang HX, Li Y, et al. Phytotherapy using blueberry leaf polyphenols to alleviate non-alcoholic fatty liver disease through improving mitochondrial function and oxidative defense[J]. Phytomedicine, 2020, 69: 153209. doi: 10.1016/j.phymed.2020.153209
|
| [44] |
Zhong XL, Huang MH, Kim HG, et al. SIRT6 protects against liver fibrosis by deacetylation and suppression of SMAD3 in hepatic stellate cells[J]. Cell Mol Gastroenterol Hepatol, 2020, 10(2): 341-364. doi: 10.1016/j.jcmgh.2020.04.005
|
| [45] |
Witayavanitkul N, Werawatganon D, Chayanupatkul M, et al. Genistein and exercise treatment reduced NASH related HDAC3, IL-13 and MMP-12 expressions in ovariectomized rats fed with high fat high fructose diet[J]. J Tradit Complement Med, 2021, 11(6): 503-512. doi: 10.1016/j.jtcme.2021.04.004
|
| [46] |
Lee J, Song JH, Chung MY, et al. 3, 4-dihydroxytoluene, a metabolite of rutin, suppresses the progression of nonalcoholic fatty liver disease in mice by inhibiting p300 histone acetyltransferase activity[J]. Acta Pharmacol Sin, 2021, 42(9): 1449-1460. doi: 10.1038/s41401-020-00571-7
|
| [47] |
Chung MY, Song JH, Lee J, et al. Tannic acid, a novel histone acetyltransferase inhibitor, prevents non-alcoholic fatty liver disease both in vivo and in vitro model[J]. Mol Metab, 2019, 19: 34-48. doi: 10.1016/j.molmet.2018.11.001
|
| [48] |
Nie KX, Gao Y, Chen S, et al. Diosgenin attenuates non-alcoholic fatty liver disease in type 2 diabetes through regulating SIRT6-related fatty acid uptake[J]. Phytomedicine, 2023, 111: 154661. doi: 10.1016/j.phymed.2023.154661
|
| [49] |
Zhang X, Jiang ZH, Jin XL, et al. Efficacy of traditional Chinese medicine combined with silibinin on nonalcoholic fatty liver disease: a meta-analysis and systematic review[J]. Medicine, 2024, 103(5): e37052. doi: 10.1097/MD.0000000000037052
|
| [50] |
He X, Li YB, Deng XY, et al. Integrative evidence construction for resveratrol treatment of nonalcoholic fatty liver disease: preclinical and clinical meta-analyses[J]. Front Pharmacol, 2023, 14: 1230783. doi: 10.3389/fphar.2023.1230783
|
| [51] |
He YH, Wang H, Lin SL, et al. Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade[J]. Biomedecine Pharmacother, 2023, 165: 115279. doi: 10.1016/j.biopha.2023.115279
|
| [1] | PEI Xin, LI Guideng, CHU Weihua. Progress of proximity labeling technology in membrane protein interaction[J]. Journal of China Pharmaceutical University, 2024, 55(2): 158-166. DOI: 10.11665/j.issn.1000-5048.2023041303 |
| [2] | ZHENG Yuting, HONG Tao, XU Kehui, WEN Minghao, YANG Jixue, WU Mengying, HANG Taijun, SONG Min. In vitro release of paclitaxel derivative liposome by paddle membrane binding assay[J]. Journal of China Pharmaceutical University, 2023, 54(6): 743-748. DOI: 10.11665/j.issn.1000-5048.2023041803 |
| [3] | XU Jianpei, XU Qunwei, WANG Xiaoqi, XIN Hongliang. Advances in biomimetic drug delivery systems based on platelet and platelet membrane[J]. Journal of China Pharmaceutical University, 2018, 49(6): 653-659. DOI: 10.11665/j.issn.1000-5048.20180603 |
| [4] | JI Yibing, DUAN Feifei, HAO Dandan, CHEN Jianqiu. Preparation and application of novel polysulfone chiral membranes for the separation of tryptophan enantiomers[J]. Journal of China Pharmaceutical University, 2017, 48(1): 53-59. DOI: 10.11665/j.issn.1000-5048.20170108 |
| [5] | WU Zheng, ZHENG Feng, DING Li. Development of in-vitro evaluation methods to access membrane permeability of drugs[J]. Journal of China Pharmaceutical University, 2011, 42(1): 16-21. |
| [6] | Construction of a Novel Fusion Expression Vector[J]. Journal of China Pharmaceutical University, 2000, (2): 65-69. |
| [7] | Preparation of Immobilized Antibody Membrane of Acoustic Immunosensor for Determination of Insulin[J]. Journal of China Pharmaceutical University, 1997, (1): 52-55. |
| [8] | Study of the Effect of Ligustrazine on Mouse Erythrocyte Membranes[J]. Journal of China Pharmaceutical University, 1994, (3): 166-169. |
| [9] | Studies on the Membrane Controlled Release Metoprolol Tablet[J]. Journal of China Pharmaceutical University, 1991, (6): 341-344. |
| [10] | PREPARATION AND APPLICATION OF NEOSTIGMINE METHYLSULFATE PVC MEMBRANE SELECTIVE ELECTRODE[J]. Journal of China Pharmaceutical University, 1988, (1): 58-61. |
Supported by: Beijing Renhe Information Technology Co., Ltd. 
Total visits：290395
DownLoad: