代谢性脂肪性肝病表观遗传学当前的挑战与展望

摘要/Abstract

摘要： 代谢性脂肪性肝病(MAFLD)是全球范围内日益严重的健康问题,其特点是肝脏脂肪沉积、炎症和纤维化,最终可能发展为肝硬化和肝细胞癌。近年来的研究发现,MAFLD中存在多种关键的表观遗传学改变,如异常的DNA甲基化模式、组蛋白修饰和microRNA及长非编码RNA的调控异常等。这些改变可能影响到MAFLD关键生物学过程,进一步促进疾病发展。此外,表观遗传学调控还与遗传、环境及生活方式等多种因素相互作用,共同影响MAFLD的发生和发展。本综述总结MAFLD表观遗传学研究的最新进展,并探讨该领域所面临的挑战及未来研究方向,旨在为未来MAFLD的诊治提供新思路。

关键词: MAFLD, NAFLD, 表观遗传学, MicroRNA, DNA甲基化

冯巩, 吕怡凡, 李芮琦, 赵文娟, 陈玉艳, 叶峰, 弥曼. 代谢性脂肪性肝病表观遗传学当前的挑战与展望[J]. 肝脏, 2023, 28(10): 1154-1157.

参考文献

[1] Sanyal AJ. Past, present and future perspectives in nonalcoholic fatty liver disease[J]. Nat Rev Gastroenterol Hepatol, 2019,6:377-386.
[2] Zeng J, Fan JG. From NAFLD to MAFLD: Not just a change in the name[J]. Hepatobiliary Pancreat Dis Int, 2022,6:511-513.
[3] Zeng X, Yuan X, Cai Q, et al. Circular RNA as An Epigenetic Regulator in Chronic Liver Diseases[J]. Cells, 2021,10(8):1945.
[4] Lopez-Sanchez GN, Dominguez-Perez M, Uribe M, et al. Non-alcoholic fatty liver disease and microRNAs expression, how it affects the development and progression of the disease[J]. Ann Hepatol, 2021,21:100212.
[5] Rovira-Llopis S, Diaz-Rua R, Grau-Del VC, et al. Characterization of Differentially Expressed Circulating miRNAs in Metabolically Healthy versus Unhealthy Obesity[J]. Biomedicines, 2021,9(3):321.
[6] Qi R, Wang J, Wang Q, et al. MicroRNA-425 controls lipogenesis and lipolysis in adipocytes[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2019,5:744-755.
[7] Zhang X, Mens M, Abozaid YJ, et al. Circulatory microRNAs as potential biomarkers for fatty liver disease: the Rotterdam study[J]. Aliment Pharmacol Ther, 2021,3:432-442.
[8] Kim TH, Lee Y, Lee YS, et al. Circulating miRNA is a useful diagnostic biomarker for nonalcoholic steatohepatitis in nonalcoholic fatty liver disease[J]. Sci Rep,2021,11(1):14639.
[9] Zhang JW, Pan HT. microRNA profiles of serum exosomes derived from children with nonalcoholic fatty liver[J]. Genes Genomics, 2022,7:879-888.
[10] Newman LA, Useckaite Z, Johnson J, et al. Selective Isolation of Liver-Derived Extracellular Vesicles Redefines Performance of miRNA Biomarkers for Non-Alcoholic Fatty Liver Disease[J]. Biomedicines, 2022,10(1):195.
[11] Hendy OM, Rabie H, El FA, et al. The Circulating Micro-RNAs (-122, -34a and -99a) as Predictive Biomarkers for Non-Alcoholic Fatty Liver Diseases[J]. Diabetes Metab Syndr Obes, 2019,12:2715-2723.
[12] Ye D, Zhang T, Lou G, et al. Plasma miR-17, miR-20a, miR-20b and miR-122 as potential biomarkers for diagnosis of NAFLD in type 2 diabetes mellitus patients[J]. Life Sci, 2018,208:201-207.
[13] Cave MC, Pinkston CM, Rai N, et al. Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Survey[J]. Environ Health Perspect, 2022,1:17003.
[14] Harrison SA, Ratziu V, Boursier J, et al. A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study[J]. Lancet Gastroenterol Hepatol, 2020,11:970-985.
[15] Johnson K, Leary PJ, Govaere O, et al. Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance[J]. JHEP Rep, 2022,2:100409.
[16] Liu XL, Pan Q, Cao H X, et al. Lipotoxic Hepatocyte-Derived Exosomal MicroRNA 192-5p Activates Macrophages Through Rictor/Akt/Forkhead Box Transcription Factor O1 Signaling in Nonalcoholic Fatty Liver Disease[J]. Hepatology, 2020,2:454-469.
[17] Ando Y, Yamazaki M, Yamada H, et al. Association of circulating miR-20a, miR-27a, and miR-126 with non-alcoholic fatty liver disease in general population[J]. Sci Rep, 2019,1:18856.
[18] Erhartova D, Cahova M, Dankova H, et al. Serum miR-33a is associated with steatosis and inflammation in patients with non-alcoholic fatty liver disease after liver transplantation[J]. PLoS One, 2019,11:e224820.
[19] Yu G, Yang Z, Peng T, et al. Circular RNAs: Rising stars in lipid metabolism and lipid disorders[J]. J Cell Physiol, 2021,7:4797-4806.
[20] Li J, Yang M, Yu Z, et al. Kidney-secreted erythropoietin lowers lipidemia via activating JAK2-STAT5 signaling in adipose tissue[J]. EBio Med, 2019,50:317-328.
[21] Zhu Y, Gui W, Lin X, et al. Knock-down of circular RNA H19 induces human adipose-derived stem cells adipogenic differentiation via a mechanism involving the polypyrimidine tract-binding protein 1[J]. Exp Cell Res, 2020,387(2):111753.
[22] Huang F, Liu H, Lei Z, et al. Long noncoding RNA CCAT1 inhibits miR-613 to promote nonalcoholic fatty liver disease via increasing LXRalpha transcription[J]. J Cell Physiol, 2020,12:9819-9833.
[23] Guo B, Cheng Y, Yao L, et al. LncRNA HOTAIR regulates the lipid accumulation in non-alcoholic fatty liver disease via miR-130b-3p/ROCK1 axis[J]. Cell Signal, 2022,90:110190.
[24] Lee J, Kim Y, Friso S, et al. Epigenetics in non-alcoholic fatty liver disease[J]. Mol Aspects Med, 2017,54:78-88.
[25] Zeybel M, Hardy T, Robinson S M, et al. Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease[J]. Clin Epigenetics, 2015,1:25.
[26] Tong J, Han CJ, Zhang JZ, et al. Hepatic Interferon Regulatory Factor 6 Alleviates Liver Steatosis and Metabolic Disorder by Transcriptionally Suppressing Peroxisome Proliferator-Activated Receptor gamma in Mice[J]. Hepatology, 2019,6:2471-2488.
[27] Hardy T, Zeybel M, Day C P, et al. Plasma DNA methylation: a potential biomarker for stratification of liver fibrosis in non-alcoholic fatty liver disease[J]. Gut, 2017,7:1321-1328.
[28] Rodriguez-Sanabria JS, Escutia-Gutierrez R, Rosas-Campos R, et al. An Update in Epigenetics in Metabolic-Associated Fatty Liver Disease[J]. Front Med (Lausanne), 2021,8:770504.
[29] Sodum N, Kumar G, Bojja S L, et al. Epigenetics in NAFLD/NASH: Targets and therapy[J]. Pharmacol Res, 2021,167:105484.
[30] Li R, Xin T, Li D, et al. Therapeutic effect of Sirtuin 3 on ameliorating nonalcoholic fatty liver disease: The role of the ERK-CREB pathway and Bnip3-mediated mitophagy[J]. Redox Bio, 2018,18:229-243.
[31] Janssen HL, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA[J]. N Engl J Med, 2013,18:1685-1694.
[32] Lima JF, Cerqueira L, Figueiredo C, et al. Anti-miRNA oligonucleotides: A comprehensive guide for design[J]. RNA Biol, 2018,3:338-352.
[33] Zhang YP, Deng YJ, Tang KR, et al. Berberine Ameliorates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats via Activation of SIRT3/AMPK/ACC Pathway[J]. Curr Med Sci,2019,1:37-43.
[34] Hosseini H, Teimouri M, Shabani M, et al. Resveratrol alleviates non-alcoholic fatty liver disease through epigenetic modification of the Nrf2 signaling pathway[J]. Int J Biochem Cell Biol, 2020,119:105667.
[35] Shen B, Feng H, Cheng J, et al. Geniposide alleviates non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signalling pathways[J]. J Cell Mol Med, 2020,9:5097-5108.
[36] Meccariello R, Santoro A, D′Angelo S, et al. The Epigenetics of the Endocannabinoid System[J]. Int J Mol Sci, 2020,3:1113.
[37] Lee DE, Lee S J, Kim SJ, et al. Curcumin Ameliorates Nonalcoholic Fatty Liver Disease through Inhibition of O-GlcNAcylation[J]. Nutrients, 2019,11.
[38] Singh S, Osna NA, Kharbanda KK. Treatment options for alcoholic and non-alcoholic fatty liver disease: A review[J]. World J Gastroenterol, 2017,36:6549-6570.