REFERENCES
1. Rui L, Lin JD. Reprogramming of hepatic metabolism and microenvironment in nonalcoholic steatohepatitis. Annu Rev Nutr 2022;42:91-113.
2. Younossi ZM, Golabi P, de Avila L, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis. J Hepatol 2019;71:793-801.
3. Ristic-Medic D, Bajerska J, Vucic V. Crosstalk between dietary patterns, obesity and nonalcoholic fatty liver disease. World J Gastroenterol 2022;28:3314-33.
4. Harrison SA, Bedossa P, Guy CD, et al; MAESTRO-NASH Investigators. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med 2024;390:497-509.
5. Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology 2010;51:679-89.
7. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 2003;33 Suppl:245-54.
8. Viscarra J, Sul HS. Epigenetic regulation of hepatic lipogenesis: role in hepatosteatosis and diabetes. Diabetes 2020;69:525-31.
9. Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. Comprehensive analysis of mRNA methylation reveals enrichment in 3’ UTRs and near stop codons. Cell 2012;149:1635-46.
10. Dominissini D, Moshitch-Moshkovitz S, Schwartz S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 2012;485:201-6.
11. Liu J, Yue Y, Han D, et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol 2014;10:93-5.
12. Ping XL, Sun BF, Wang L, et al. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res 2014;24:177-89.
13. Murakami S, Jaffrey SR. Hidden codes in mRNA: control of gene expression by m6A. Mol Cell 2022;82:2236-51.
14. Shi H, Wei J, He C. Where, when, and how: context-dependent functions of RNA methylation writers, readers, and erasers. Mol Cell 2019;74:640-50.
15. Zaccara S, Ries RJ, Jaffrey SR. Reading, writing and erasing mRNA methylation. Nat Rev Mol Cell Biol 2019;20:608-24.
16. Lin Y, Dong C, Zhou BP. Epigenetic regulation of EMT: the snail story. Curr Pharm Des 2014;20:1698-705.
17. Zhou W, Gross KM, Kuperwasser C. Molecular regulation of Snai2 in development and disease. J Cell Sci 2019;132:jcs235127.
18. Batlle E, Sancho E, Francí C, et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2000;2:84-9.
19. Peinado H, Ballestar E, Esteller M, Cano A. Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Mol Cell Biol 2004;24:306-19.
20. Kim MH, Li Y, Zheng Q, et al. LepRb+ cell-specific deletion of slug mitigates obesity and nonalcoholic fatty liver disease in mice. J Clin Invest 2023;133:e156722.
21. Sun C, Jiang L, Liu Y, et al. Adipose snail1 regulates lipolysis and lipid partitioning by suppressing adipose triacylglycerol lipase expression. Cell Rep 2016;17:2015-27.
22. Liu Y, Jiang L, Sun C, et al. Insulin/snail1 axis ameliorates fatty liver disease by epigenetically suppressing lipogenesis. Nat Commun 2018;9:2751.
23. Liu Y, Lin H, Jiang L, et al. Hepatic slug epigenetically promotes liver lipogenesis, fatty liver disease, and type 2 diabetes. J Clin Invest 2020;130:2992-3004.
24. Wang P, Kang Q, Wu WS, Rui L. Hepatic Snai1 and Snai2 promote liver regeneration and suppress liver fibrosis in mice. Cell Rep 2024;43:113875.
25. Sekiya S, Suzuki A. Glycogen synthase kinase 3 β-dependent Snail degradation directs hepatocyte proliferation in normal liver regeneration. Proc Natl Acad Sci U S A 2011;108:11175-80.
26. Rowe RG, Lin Y, Shimizu-Hirota R, et al. Hepatocyte-derived Snail1 propagates liver fibrosis progression. Mol Cell Biol 2011;31:2392-403.
27. Jia G, Fu Y, Zhao X, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol 2011;7:885-7.
28. Fu Y, Jia G, Pang X, et al. FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA. Nat Commun 2013;4:1798.
29. Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007;316:889-94.
30. Dina C, Meyre D, Gallina S, et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007;39:724-6.
31. Scott LJ, Mohlke KL, Bonnycastle LL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 2007;316:1341-5.
32. Scuteri A, Sanna S, Chen WM, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007;3:e115.
33. Thorleifsson G, Walters GB, Gudbjartsson DF, et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 2009;41:18-24.
34. Willer CJ, Speliotes EK, Loos RJ, et al; Wellcome Trust Case Control Consortium, Genetic Investigation of ANthropometric Traits Consortium. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009;41:25-34.
35. Chen A, Chen X, Cheng S, et al. FTO promotes SREBP1c maturation and enhances CIDEC transcription during lipid accumulation in HepG2 cells. Biochim Biophys Acta Mol Cell Biol Lipids 2018;1863:538-48.
36. Kang H, Zhang Z, Yu L, Li Y, Liang M, Zhou L. FTO reduces mitochondria and promotes hepatic fat accumulation through RNA demethylation. J Cell Biochem 2018;119:5676-85.
37. Hu Y, Feng Y, Zhang L, et al. GR-mediated FTO transactivation induces lipid accumulation in hepatocytes via demethylation of m6A on lipogenic mRNAs. RNA Biol 2020;17:930-42.
38. Salisbury DA, Casero D, Zhang Z, et al. Transcriptional regulation of N6-methyladenosine orchestrates sex-dimorphic metabolic traits. Nat Metab 2021;3:940-53.
39. Wang YF, Zhang WL, Li ZX, et al. METTL14 downregulation drives S100A4+ monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression. Signal Transduct Target Ther 2024;9:91.
40. Li X, Yuan B, Lu M, et al. The methyltransferase METTL3 negatively regulates nonalcoholic steatohepatitis (NASH) progression. Nat Commun 2021;12:7213.
41. Zhong X, Yu J, Frazier K, et al. Circadian clock regulation of hepatic lipid metabolism by modulation of m6A mRNA methylation. Cell Rep 2018;25:1816-28.e4.
42. Xie W, Ma LL, Xu YQ, Wang BH, Li SM. METTL3 inhibits hepatic insulin sensitivity via N6-methyladenosine modification of Fasn mRNA and promoting fatty acid metabolism. Biochem Biophys Res Commun 2019;518:120-6.
43. Wang W, Yan J, Han L, Zou ZL, Xu AL. Silencing METTL14 alleviates liver injury in non-alcoholic fatty liver disease by regulating mitochondrial homeostasis. Biomol Biomed 2024;24:505-19.
44. Yang Y, Cai J, Yang X, et al. Dysregulated m6A modification promotes lipogenesis and development of non-alcoholic fatty liver disease and hepatocellular carcinoma. Mol Ther 2022;30:2342-53.
45. Peng Z, Gong Y, Wang X, et al. METTL3-m6A-rubicon axis inhibits autophagy in nonalcoholic fatty liver disease. Mol Ther 2022;30:932-46.
46. Zhou B, Liu C, Xu L, et al. N6 -methyladenosine reader protein YT521-B homology domain-containing 2 suppresses liver steatosis by regulation of mRNA stability of lipogenic genes. Hepatology 2021;73:91-103.
47. Zhang X, Yin H, Zhang X, et al. N6-methyladenosine modification governs liver glycogenesis by stabilizing the glycogen synthase 2 mRNA. Nat Commun 2022;13:7038.
48. Wei J, Harada BT, Lu D, et al. HRD1-mediated METTL14 degradation regulates m6A mRNA modification to suppress ER proteotoxic liver disease. Mol Cell 2021;81:5052-65.e6.
49. Wang S, Chen S, Sun J, et al. m6A modification-tuned sphingolipid metabolism regulates postnatal liver development in male mice. Nat Metab 2023;5:842-60.
50. Li R, Yan X, Xiao C, et al. FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC. Nat Commun 2024;15:4760.
51. Cao X, Shu Y, Chen Y, et al. Mettl14-mediated m6A modification facilitates liver regeneration by maintaining endoplasmic reticulum homeostasis. Cell Mol Gastroenterol Hepatol 2021;12:633-51.
52. Pan Y, Chen H, Zhang X, et al. METTL3 drives NAFLD-related hepatocellular carcinoma and is a therapeutic target for boosting immunotherapy. Cell Rep Med 2023;4:101144.
53. Kan RL, Chen J, Sallam T. Crosstalk between epitranscriptomic and epigenetic mechanisms in gene regulation. Trends Genet 2022;38:182-93.
54. Xu Z, Xie T, Sui X, et al. Crosstalk between histone and m6A modifications and emerging roles of m6A RNA Methylation. Front Genet 2022;13:908289.
55. Xu QC, Tien YC, Shi YH, et al. METTL3 promotes intrahepatic cholangiocarcinoma progression by regulating IFIT2 expression in an m6A-YTHDF2-dependent manner. Oncogene 2022;41:1622-33.
56. Du QY, Huo FC, Du WQ, et al. METTL3 potentiates progression of cervical cancer by suppressing ER stress via regulating m6A modification of TXNDC5 mRNA. Oncogene 2022;41:4420-32.
57. Wang Q, Chen C, Ding Q, et al. METTL3-mediated m6A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance. Gut 2020;69:1193-205.
58. Xiong J, He J, Zhu J, et al. Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells. Mol Cell 2022;82:1660-77.e10.
59. Chen X, Xu M, Xu X, et al. METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer. Mol Cancer 2020;19:106.
60. Wei J, He C. Chromatin and transcriptional regulation by reversible RNA methylation. Curr Opin Cell Biol 2021;70:109-15.
61. Wang Y, Li Y, Yue M, et al. N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nat Neurosci 2018;21:195-206.
62. Chen J, Zhang YC, Huang C, et al. m6A regulates neurogenesis and neuronal development by modulating histone methyltransferase Ezh2. Genomics Proteomics Bioinformatics 2019;17:154-68.
63. Dou X, Huang L, Xiao Y, et al. METTL14 is a chromatin regulator independent of its RNA N6-methyladenosine methyltransferase activity. Protein Cell 2023;14:683-97.
64. Shi Y, Qi W. Histone modifications in NAFLD: mechanisms and potential therapy. Int J Mol Sci 2023;24:14653.
65. Fu S, Yu M, Tan Y, Liu D. Role of histone deacetylase on nonalcoholic fatty liver disease. Expert Rev Gastroenterol Hepatol 2021;15:353-61.
66. Noce B, Di Bello E, Fioravanti R, Mai A. LSD1 inhibitors for cancer treatment: focus on multi-target agents and compounds in clinical trials. Front Pharmacol 2023;14:1120911.
67. Ramms B, Pollow DP, Zhu H, et al. Systemic LSD1 inhibition prevents aberrant remodeling of metabolism in obesity. Diabetes 2022;71:2513-29.
68. Peng S, Xiao W, Ju D, et al. Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1. Sci Transl Med 2019;11:eaau7116.
69. Huang Y, Yan J, Li Q, et al. Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5. Nucleic Acids Res 2015;43:373-84.
70. Dang Y, Xu J, Yang Y, et al. Ling-gui-zhu-gan decoction alleviates hepatic steatosis through SOCS2 modification by N6-methyladenosine. Biomed Pharmacother 2020;127:109976.
71. Wu J, Li Y, Yu J, et al. Resveratrol attenuates high-fat diet induced hepatic lipid homeostasis disorder and decreases m6A RNA methylation. Front Pharmacol 2020;11:568006.
72. Luo P, Li S, Jing W, Tu J, Long X. N6-methyladenosine RNA modification in nonalcoholic fatty liver disease. Trends Endocrinol Metab 2023;34:838-48.
73. Li W, Ng CH, Quek J, et al. The growing prevalence of nonalcoholic fatty liver disease (NAFLD), determined by fatty liver index, amongst young adults in the United States. A 20-year experience. Metab Target Organ Damage 2022;2:19.
