Login Register Cart 0
Generic placeholder image

Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Histone Methylation Regulation as a Potential Target for Non-alcoholic Fatty Liver Disease

Author(s): Yuanbin Liu and Mingkai Chen*

Volume 24, Issue 6, 2023

Published on: 05 June, 2023

Page: [465 - 476] Pages: 12

DOI: 10.2174/1389203724666230526155643

Price: $65

Abstract

Epigenetic modulations are currently emerging as promising targets in metabolic diseases, including non-alcoholic fatty liver disease (NAFLD), for their roles in pathogenesis and therapeutic potential. The molecular mechanisms and modulation potential of histone methylation as a histone post-transcriptional modification in NAFLD have been recently addressed. However, a detailed overview of the histone methylation regulation in NAFLD is lacking. In this review, we comprehensively summarize the mechanisms of histone methylation regulation in NAFLD. We conducted a comprehensive database search in the PubMed database with the keywords 'histone', 'histone methylation', 'NAFLD', and 'metabolism' without time restriction. Reference lists of key documents were also reviewed to include potentially omitted articles. It has been reported that these enzymes can interact with other transcription factors or receptors under pro-NAFLD conditions, such as nutritional stress, which lead to recruitment to the promoters or transcriptional regions of key genes involved in glycolipid metabolism, ultimately regulating gene transcriptional activity to influence the expression. Histone methylation regulation has been implicated in mediating metabolic crosstalk between tissues or organs in NAFLD and serves a critical role in NAFLD development and progression. Some dietary interventions or agents targeting histone methylation have been suggested to improve NAFLD; however, there is still a lack of additional research and clinical translational relevance. In conclusion, histone methylation/demethylation has demonstrated an important regulatory role in NAFLD by mediating the expression of key glycolipid metabolism-related genes, and more research is needed in the future to explore its potential as a therapeutic target.

Keywords: Epigenetics, histone methylation, non-alcoholic fatty liver disease, lipid metabolism, therapy, NAFLD.

« Previous Next »
Graphical Abstract

[1]
Riazi, K.; Azhari, H.; Charette, J.H.; Underwood, F.E.; King, J.A.; Afshar, E.E.; Swain, M.G.; Congly, S.E.; Kaplan, G.G.; Shaheen, A.A. The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis. Lancet Gastroenterol. Hepatol., 2022, 7(9), 851-861.
[http://dx.doi.org/10.1016/S2468-1253(22)00165-0] [PMID: 35798021]
[2]
Powell, E.E.; Wong, V.W.S.; Rinella, M. Non-alcoholic fatty liver disease. Lancet, 2021, 397(10290), 2212-2224.
[http://dx.doi.org/10.1016/S0140-6736(20)32511-3] [PMID: 33894145]
[3]
Petroni, M.L.; Brodosi, L.; Bugianesi, E.; Marchesini, G. Management of non-alcoholic fatty liver disease. BMJ, 2021, 372, m4747.
[http://dx.doi.org/10.1136/bmj.m4747] [PMID: 33461969]
[4]
Trépo, E.; Valenti, L. Update on NAFLD genetics: From new variants to the clinic. J. Hepatol., 2020, 72(6), 1196-1209.
[http://dx.doi.org/10.1016/j.jhep.2020.02.020] [PMID: 32145256]
[5]
Ling, C.; Rönn, T. Epigenetics in human obesity and type 2 diabetes. Cell Metab., 2019, 29(5), 1028-1044.
[http://dx.doi.org/10.1016/j.cmet.2019.03.009] [PMID: 30982733]
[6]
Zhang, L.; Lu, Q.; Chang, C. Epigenetics in health and disease. Adv. Exp. Med. Biol., 2020, 1253, 3-55.
[http://dx.doi.org/10.1007/978-981-15-3449-2_1] [PMID: 32445090]
[7]
Sodum, N.; Kumar, G.; Bojja, S.L.; Kumar, N.; Rao, C.M. Epigenetics in NAFLD/NASH: Targets and therapy. Pharmacol. Res., 2021, 167, 105484.
[http://dx.doi.org/10.1016/j.phrs.2021.105484] [PMID: 33771699]
[8]
Kim, J.; Lee, H.; Yi, S.J.; Kim, K. Gene regulation by histone-modifying enzymes under hypoxic conditions: A focus on histone methylation and acetylation. Exp. Mol. Med., 2022, 54(7), 878-889.
[http://dx.doi.org/10.1038/s12276-022-00812-1] [PMID: 35869366]
[9]
Tolsma, T.O.; Hansen, J.C. Post-translational modifications and chromatin dynamics. Essays Biochem., 2019, 63(1), 89-96.
[http://dx.doi.org/10.1042/EBC20180067] [PMID: 31015385]
[10]
Zhang, Y.; Sun, Z.; Jia, J.; Du, T.; Zhang, N.; Tang, Y.; Fang, Y.; Fang, D. Overview of histone modification. Adv. Exp. Med. Biol., 2021, 1283, 1-16.
[http://dx.doi.org/10.1007/978-981-15-8104-5_1] [PMID: 33155134]
[11]
Cai, Q.; Gan, C.; Tang, C.; Wu, H.; Gao, J. Mechanism and therapeutic opportunities of histone modifications in chronic liver disease. Front. Pharmacol., 2021, 12, 784591.
[http://dx.doi.org/10.3389/fphar.2021.784591] [PMID: 34887768]
[12]
Lim, H.J.; Kim, M. EZH2 as a potential target for NAFLD therapy. Int. J. Mol. Sci., 2020, 21(22), 8617.
[http://dx.doi.org/10.3390/ijms21228617] [PMID: 33207561]
[13]
Michalak, E.M.; Burr, M.L.; Bannister, A.J.; Dawson, M.A. The roles of DNA, RNA and histone methylation in ageing and cancer. Nat. Rev. Mol. Cell Biol., 2019, 20(10), 573-589.
[http://dx.doi.org/10.1038/s41580-019-0143-1] [PMID: 31270442]
[14]
Fyodorov, D.V.; Zhou, B.R.; Skoultchi, A.I.; Bai, Y. Emerging roles of linker histones in regulating chromatin structure and function. Nat. Rev. Mol. Cell Biol., 2018, 19(3), 192-206.
[http://dx.doi.org/10.1038/nrm.2017.94] [PMID: 29018282]
[15]
Zhou, B.R.; Bai, Y. Chromatin structures condensed by linker histones. Essays Biochem., 2019, 63(1), 75-87.
[http://dx.doi.org/10.1042/EBC20180056] [PMID: 31015384]
[16]
Castillo-Aguilera, O.; Depreux, P.; Halby, L.; Arimondo, P.; Goossens, L. DNA methylation targeting: The DNMT/HMT crosstalk challenge. Biomolecules, 2017, 7(4), 3.
[http://dx.doi.org/10.3390/biom7010003] [PMID: 28067760]
[17]
Gong, F.; Miller, K.M. Histone methylation and the DNA damage response. Mutat. Res. Rev. Mutat. Res., 2019, 780, 37-47.
[http://dx.doi.org/10.1016/j.mrrev.2017.09.003] [PMID: 31395347]
[18]
Zhang, X.; Huang, Y.; Shi, X. Emerging roles of lysine methylation on non-histone proteins. Cell. Mol. Life Sci., 2015, 72(22), 4257-4272.
[http://dx.doi.org/10.1007/s00018-015-2001-4] [PMID: 26227335]
[19]
Zhao, S.; Chuh, K.N.; Zhang, B.; Dul, B.E.; Thompson, R.E.; Farrelly, L.A.; Liu, X.; Xu, N.; Xue, Y.; Roeder, R.G.; Maze, I.; Muir, T.W.; Li, H. Histone H3Q5 serotonylation stabilizes H3K4 methylation and potentiates its readout. Proc. Natl. Acad. Sci., 2021, 118(6), e2016742118.
[http://dx.doi.org/10.1073/pnas.2016742118] [PMID: 33526675]
[20]
Black, J.C.; Van Rechem, C.; Whetstine, J.R. Histone lysine methylation dynamics: Establishment, regulation, and biological impact. Mol. Cell, 2012, 48(4), 491-507.
[http://dx.doi.org/10.1016/j.molcel.2012.11.006] [PMID: 23200123]
[21]
Buzzetti, E.; Pinzani, M.; Tsochatzis, E.A. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism, 2016, 65(8), 1038-1048.
[http://dx.doi.org/10.1016/j.metabol.2015.12.012] [PMID: 26823198]
[22]
Bessone, F.; Razori, M.V.; Roma, M.G. Molecular pathways of nonalcoholic fatty liver disease development and progression. Cell. Mol. Life Sci., 2019, 76(1), 99-128.
[http://dx.doi.org/10.1007/s00018-018-2947-0] [PMID: 30343320]
[23]
Loomba, R.; Friedman, S.L.; Shulman, G.I. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell, 2021, 184(10), 2537-2564.
[http://dx.doi.org/10.1016/j.cell.2021.04.015] [PMID: 33989548]
[24]
Anstee, Q.M.; Reeves, H.L.; Kotsiliti, E.; Govaere, O.; Heikenwalder, M. From NASH to HCC: Current concepts and future challenges. Nat. Rev. Gastroenterol. Hepatol., 2019, 16(7), 411-428.
[http://dx.doi.org/10.1038/s41575-019-0145-7] [PMID: 31028350]
[25]
Goldsworthy, M.; Absalom, N.L.; Schröter, D.; Matthews, H.C.; Bogani, D.; Moir, L.; Long, A.; Church, C.; Hugill, A.; Anstee, Q.M.; Goldin, R.; Thursz, M.; Hollfelder, F.; Cox, R.D. Mutations in Mll2, an H3K4 methyltransferase, result in insulin resistance and impaired glucose tolerance in mice. PLoS One, 2013, 8(6), e61870.
[http://dx.doi.org/10.1371/journal.pone.0061870] [PMID: 23826075]
[26]
Kim, D.H.; Kim, J.; Kwon, J.S.; Sandhu, J.; Tontonoz, P.; Lee, S.K.; Lee, S.; Lee, J.W. Critical roles of the histone methyltransferase MLL4/KMT2D in murine hepatic steatosis directed by ABL1 and PPARγ2. Cell Rep., 2016, 17(6), 1671-1682.
[http://dx.doi.org/10.1016/j.celrep.2016.10.023] [PMID: 27806304]
[27]
Han, Y.H.; Kim, H.J.; Choi, H.; Lee, S.; Lee, M.O. RORα autoregulates its transcription via MLL4-associated enhancer remodeling in the liver. Life Sci., 2020, 256, 118007.
[http://dx.doi.org/10.1016/j.lfs.2020.118007] [PMID: 32598934]
[28]
Kim, J.; Lee, B.; Kim, D.H.; Yeon, J.G.; Lee, J.; Park, Y.; Lee, Y.; Lee, S.K.; Lee, S.; Lee, J.W. UBE3A suppresses overnutrition‐induced expression of the steatosis target genes of MLL4 by degrading MLL4. Hepatology, 2019, 69(3), 1122-1134.
[http://dx.doi.org/10.1002/hep.30284] [PMID: 30230575]
[29]
Talbert, P.B.; Henikoff, S. Histone variants at a glance. J. Cell Sci., 2021, 134(6), jcs244749.
[http://dx.doi.org/10.1242/jcs.244749] [PMID: 33771851]
[30]
Podrini, C.; Koffas, A.; Chokshi, S.; Vinciguerra, M.; Lelliott, C.J.; White, J.K.; Adissu, H.A.; Williams, R.; Greco, A. MacroH2A1 isoforms are associated with epigenetic markers for activation of lipogenic genes in fat‐induced steatosis. FASEB J., 2015, 29(5), 1676-1687.
[http://dx.doi.org/10.1096/fj.14-262717] [PMID: 25526730]
[31]
Tucker, B.; Li, H.; Long, X.; Rye, K.A.; Ong, K.L. Fibroblast growth factor 21 in non-alcoholic fatty liver disease. Metabolism, 2019, 101, 153994.
[http://dx.doi.org/10.1016/j.metabol.2019.153994] [PMID: 31672443]
[32]
Tong, X.; Zhang, D.; Buelow, K.; Guha, A.; Arthurs, B.; Brady, H.J.M.; Yin, L. Recruitment of histone methyltransferase G9a mediates transcriptional repression of Fgf21 gene by E4BP4 protein. J. Biol. Chem., 2013, 288(8), 5417-5425.
[http://dx.doi.org/10.1074/jbc.M112.433482] [PMID: 23283977]
[33]
Zhang, W.; Yang, D.; Yuan, Y.; Liu, C.; Chen, H.; Zhang, Y.; Wang, Q.; Petersen, R.B.; Huang, K.; Zheng, L. Muscular G9a regulates muscle-liver-fat axis by musclin under overnutrition in female mice. Diabetes, 2020, 69(12), 2642-2654.
[http://dx.doi.org/10.2337/db20-0437] [PMID: 32994276]
[34]
Pande, P.; Zhong, X.; Ku, W.W. Histone methyltransferase g9a regulates expression of nuclear receptors and cytochrome P450 enzymes in heparg cells at basal level and in fatty acid induced steatosis. Drug Metab. Dispos., 2020, 48(12), 1321-1329.
[http://dx.doi.org/10.1124/dmd.120.000195] [PMID: 33077425]
[35]
Ohno, M.; Kanayama, T.; Moore, R.; Ray, M.; Negishi, M. The roles of co-chaperone CCRP/DNAJC7 in Cyp2b10 gene activation and steatosis development in mouse livers. PLoS One, 2014, 9(12), e115663.
[http://dx.doi.org/10.1371/journal.pone.0115663] [PMID: 25542016]
[36]
Yu, H.; Wu, J.; Yang, M.; Guo, J.; Zheng, L.; Peng, M.; Zhang, Q.; Xiang, Y.; Cao, J.; Shen, W. Involvement of liver X receptor alpha in histone modifications across the target fatty acid synthase gene. Lipids, 2012, 47(3), 249-257.
[http://dx.doi.org/10.1007/s11745-011-3635-0] [PMID: 22160584]
[37]
de Gregorio, E.; Colell, A.; Morales, A.; Marí, M. Relevance of SIRT1-NF-κB axis as therapeutic target to ameliorate inflammation in liver disease. Int. J. Mol. Sci., 2020, 21(11), 3858.
[http://dx.doi.org/10.3390/ijms21113858] [PMID: 32485811]
[38]
Dziewulska, A.; Dobosz, A.M.; Dobrzyn, A.; Smolinska, A.; Kolczynska, K.; Ntambi, J.M.; Dobrzyn, P. SCD1 regulates the AMPK/SIRT1 pathway and histone acetylation through changes in adenine nucleotide metabolism in skeletal muscle. J. Cell. Physiol., 2020, 235(2), 1129-1140.
[http://dx.doi.org/10.1002/jcp.29026] [PMID: 31241768]
[39]
Shao, J.; Li, L.; Xu, H.; Yang, L.; Bian, Y.; Fang, M.; Xu, Y. Suv39h2 deficiency ameliorates diet-induced steatosis in mice. Biochem. Biophys. Res. Commun., 2017, 485(3), 658-664.
[http://dx.doi.org/10.1016/j.bbrc.2017.02.093] [PMID: 28232186]
[40]
Fan, Z.; Li, L.; Li, M.; Zhang, X.; Hao, C.; Yu, L.; Zeng, S.; Xu, H.; Fang, M.; Shen, A.; Jenuwein, T.; Xu, Y. The histone methyltransferase Suv39h2 contributes to nonalcoholic steatohepatitis in mice. Hepatology, 2017, 65(6), 1904-1919.
[http://dx.doi.org/10.1002/hep.29127] [PMID: 28244120]
[41]
Vella, S.; Gnani, D.; Crudele, A.; Ceccarelli, S.; De Stefanis, C.; Gaspari, S.; Nobili, V.; Locatelli, F.; Marquez, V.; Rota, R.; Alisi, A. EZH2 down-regulation exacerbates lipid accumulation and inflammation in in vitro and in vivo NAFLD. Int. J. Mol. Sci., 2013, 14(12), 24154-24168.
[http://dx.doi.org/10.3390/ijms141224154] [PMID: 24351808]
[42]
Lee, S.; Woo, D.C.; Kang, J.; Ra, M.; Kim, K.H.; Lee, S.R.; Choi, D.K.; Lee, H.; Hong, K.B.; Min, S.H.; Lee, Y.; Yu, J.H. The role of the histone methyltransferase EZH2 in liver inflammation and fibrosis in STAM NASH mice. Biology, 2020, 9(5), 93.
[http://dx.doi.org/10.3390/biology9050093] [PMID: 32370249]
[43]
Wu, F.; Xu, L.; Tu, Y.; Cheung, O.K.W.; Szeto, L.L.M.; Mok, M.T.S.; Yang, W.; Kang, W.; Cao, Q.; Lai, P.B.S.; Chan, S.L.; Tan, P.; Sung, J.J.Y.; Yip, K.Y.; Cheng, A.S.L.; To, K.F. Sirtuin 7 super-enhancer drives epigenomic reprogramming in hepatocarcinogenesis. Cancer Lett., 2022, 525, 115-130.
[http://dx.doi.org/10.1016/j.canlet.2021.10.039] [PMID: 34736960]
[44]
Shuai, L.; Li, B.H.; Jiang, H.W.; Yang, L.; Li, J.; Li, J.Y. DOT1L regulates thermogenic adipocyte differentiation and function via modulating H3K79 methylation. Diabetes, 2021, 70(6), 1317-1333.
[http://dx.doi.org/10.2337/db20-1110] [PMID: 33795413]
[45]
Beck, D.B.; Oda, H.; Shen, S.S.; Reinberg, D. PR-Set7 and H4K20me1: At the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription. Genes Dev., 2012, 26(4), 325-337.
[http://dx.doi.org/10.1101/gad.177444.111] [PMID: 22345514]
[46]
Nikolaou, K.C.; Moulos, P.; Harokopos, V.; Chalepakis, G.; Talianidis, I. Kmt5a controls hepatic metabolic pathways by facilitating RNA Pol II release from promoter-proximal regions. Cell Rep., 2017, 20(4), 909-922.
[http://dx.doi.org/10.1016/j.celrep.2017.07.003] [PMID: 28746875]
[47]
Stopa, N.; Krebs, J.E.; Shechter, D. The PRMT5 arginine methyltransferase: Many roles in development, cancer and beyond. Cell. Mol. Life Sci., 2015, 72(11), 2041-2059.
[http://dx.doi.org/10.1007/s00018-015-1847-9] [PMID: 25662273]
[48]
Wang, D.; Tan, K.S.; Zeng, W.; Li, S.; Wang, Y.; Xu, F.; Tan, W. Hepatocellular BChE as a therapeutic target to ameliorate hypercholesterolemia through PRMT5 selective degradation to restore LDL receptor transcription. Life Sci., 2022, 293, 120336.
[http://dx.doi.org/10.1016/j.lfs.2022.120336] [PMID: 35065166]
[49]
Huang, L.; Liu, J.; Zhang, X.O.; Sibley, K.; Najjar, S.M.; Lee, M.M.; Wu, Q. Inhibition of protein arginine methyltransferase 5 enhances hepatic mitochondrial biogenesis. J. Biol. Chem., 2018, 293(28), 10884-10894.
[http://dx.doi.org/10.1074/jbc.RA118.002377] [PMID: 29773653]
[50]
Yang, M.; Lin, X.; Segers, F.; Suganthan, R.; Hildrestrand, G.A.; Rinholm, J.E.; Aas, P.A.; Sousa, M.M.L.; Holm, S.; Bolstad, N.; Warren, D.; Berge, R.K.; Johansen, R.F.; Yndestad, A.; Kristiansen, E.; Klungland, A.; Luna, L.; Eide, L.; Halvorsen, B.; Aukrust, P.; Bjørås, M. OXR1A, a Coactivator of PRMT5 Regulating Histone Arginine Methylation. Cell Rep., 2020, 30(12), 4165-4178.
[http://dx.doi.org/10.1016/j.celrep.2020.02.063] [PMID: 32209476]
[51]
Zhang, B.; Zhou, B.; Xiao, M.; Li, H.; Guo, L.; Wang, M.; Yu, S.; Ye, Q. KDM5C represses FASN-Mediated lipid metabolism to exert tumor suppressor activity in intrahepatic cholangiocarcinoma. Front. Oncol., 2020, 10, 1025.
[http://dx.doi.org/10.3389/fonc.2020.01025] [PMID: 32714863]
[52]
Nagaoka, K.; Hino, S.; Sakamoto, A.; Anan, K.; Takase, R.; Umehara, T.; Yokoyama, S.; Sasaki, Y.; Nakao, M. Lysine-specific demethylase 2 suppresses lipid influx and metabolism in hepatic cells. Mol. Cell. Biol., 2015, 35(7), 1068-1080.
[http://dx.doi.org/10.1128/MCB.01404-14] [PMID: 25624347]
[53]
Cao, Y.; Tang, L.; Du, K.; Paraiso, K.; Sun, Q.; Liu, Z.; Ye, X.; Fang, Y.; Yuan, F.; Chen, H.; Chen, Y.; Wang, X.; Yu, C.; Blitz, I.L.; Wang, P.H.; Huang, L.; Cheng, H.; Lu, X.; Cho, K.W.Y.; Seldin, M.; Fang, Z.; Yang, Q. Anterograde regulation of mitochondrial genes and FGF21 signaling by hepatic LSD1. JCI Insight, 2021, 6(17), e147692.
[http://dx.doi.org/10.1172/jci.insight.147692] [PMID: 34314389]
[54]
Ramms, B.; Pollow, D.P.; Zhu, H.; Nora, C.; Harrington, A.R.; Omar, I.; Gordts, P.L.S.M.; Wortham, M.; Sander, M. Systemic LSD1 inhibition prevents aberrant remodeling of metabolism in obesity. Diabetes, 2022, 71(12), 2513-2529.
[http://dx.doi.org/10.2337/db21-1131] [PMID: 36162056]
[55]
Kang, C.; Saso, K.; Ota, K.; Kawazu, M.; Ueda, T.; Okada, H. JMJD2B/KDM4B inactivation in adipose tissues accelerates obesity and systemic metabolic abnormalities. Genes Cells, 2018, 23(9), 767-777.
[http://dx.doi.org/10.1111/gtc.12627] [PMID: 30073721]
[56]
Kim, J.H.; Jung, D.Y.; Nagappan, A.; Jung, M.H. Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPARγ2. Sci. Rep., 2018, 8(1), 13734.
[http://dx.doi.org/10.1038/s41598-018-31953-x] [PMID: 30214048]
[57]
Kim, J.H.; Jung, D.Y.; Kim, H.R.; Jung, M.H. Histone H3K9 demethylase JMJD2B plays a role in LXRα-dependent lipogenesis. Int. J. Mol. Sci., 2020, 21(21), 8313.
[http://dx.doi.org/10.3390/ijms21218313]
[58]
Chu, Q.; Gu, X.; Zheng, Q.; Zhu, H. Regulatory mechanism of HIF-1α and its role in liver diseases: A narrative review. Ann. Transl. Med., 2022, 10(2), 109.
[http://dx.doi.org/10.21037/atm-21-4222] [PMID: 35282052]
[59]
Fan, Z.; Li, Z.; Yang, Y.; Liu, S.; Guo, J.; Xu, Y. HIF-1α coordinates epigenetic activation of SIAH1 in hepatocytes in response to nutritional stress. Biochim. Biophys. Acta. Gene Regul. Mech., 2017, 1860(10), 1037-1046.
[http://dx.doi.org/10.1016/j.bbagrm.2017.08.002] [PMID: 28843785]
[60]
Bricambert, J.; Alves-Guerra, M.C.; Esteves, P.; Prip-Buus, C.; Bertrand-Michel, J.; Guillou, H.; Chang, C.J.; Vander Wal, M.N.; Canonne-Hergaux, F.; Mathurin, P.; Raverdy, V.; Pattou, F.; Girard, J.; Postic, C.; Dentin, R. The histone demethylase Phf2 acts as a molecular checkpoint to prevent NAFLD progression during obesity. Nat. Commun., 2018, 9(1), 2092.
[http://dx.doi.org/10.1038/s41467-018-04361-y] [PMID: 29844386]
[61]
Lane, E.A.; Choi, D.W.; Garcia-Haro, L.; Levine, Z.G.; Tedoldi, M.; Walker, S.; Danial, N.N. HCF-1 Regulates De Novo Lipogenesis through a Nutrient-Sensitive Complex with ChREBP. Mol. Cell, 2019, 75(2), 357-371.e7.
[http://dx.doi.org/10.1016/j.molcel.2019.05.019] [PMID: 31227231]
[62]
Viscarra, J.A.; Wang, Y.; Nguyen, H.P.; Choi, Y.G.; Sul, H.S. Histone demethylase JMJD1C is phosphorylated by mTOR to activate de novo lipogenesis. Nat. Commun., 2020, 11(1), 796.
[http://dx.doi.org/10.1038/s41467-020-14617-1] [PMID: 32034158]
[63]
Liu, Y.; Lin, H.; Jiang, L.; Shang, Q.; Yin, L.; Lin, J.D.; Wu, W.S.; Rui, L. Hepatic Slug epigenetically promotes liver lipogenesis, fatty liver disease, and type 2 diabetes. J. Clin. Invest., 2020, 130(6), 2992-3004.
[http://dx.doi.org/10.1172/JCI128073] [PMID: 32365055]
[64]
Seok, S.; Kim, Y.C.; Byun, S.; Choi, S.; Xiao, Z.; Iwamori, N.; Zhang, Y.; Wang, C.; Ma, J.; Ge, K.; Kemper, B.; Kemper, J.K. Fasting-induced JMJD3 histone demethylase epigenetically activates mitochondrial fatty acid β-oxidation. J. Clin. Invest., 2018, 128(7), 3144-3159.
[http://dx.doi.org/10.1172/JCI97736] [PMID: 29911994]
[65]
Byun, S.; Seok, S.; Kim, Y.C.; Zhang, Y.; Yau, P.; Iwamori, N.; Xu, H.E.; Ma, J.; Kemper, B.; Kemper, J.K. Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase. Nat. Commun., 2020, 11(1), 807.
[http://dx.doi.org/10.1038/s41467-020-14384-z] [PMID: 32042044]
[66]
Zhao, F.; Ke, J.; Pan, W.; Pan, H.; Shen, M. Synergistic effects of ISL1 and KDM6B on non-alcoholic fatty liver disease through the regulation of SNAI1. Mol. Med., 2022, 28(1), 12.
[http://dx.doi.org/10.1186/s10020-021-00428-7] [PMID: 35100965]
[67]
Roy, S.; Abudu, A.; Salinas, I.; Sinha, N.; Cline-Fedewa, H.; Yaw, A.M.; Qi, W.; Lydic, T.A.; Takahashi, D.L.; Hennebold, J.D.; Hoffmann, H.M.; Wang, J.; Sen, A. Androgen-mediated perturbation of the hepatic circadian system through epigenetic modulation promotes NAFLD in PCOS mice. Endocrinology, 2022, 163(10), bqac127.
[http://dx.doi.org/10.1210/endocr/bqac127] [PMID: 35933634]
[68]
Kim, J.H.; Nagappan, A.; Jung, D.; Suh, N.; Jung, M. Histone demethylase KDM7A contributes to the development of hepatic steatosis by targeting diacylglycerol acyltransferase 2. Int. J. Mol. Sci., 2021, 22(20), 11085.
[http://dx.doi.org/10.3390/ijms222011085] [PMID: 34681759]
[69]
Li, F.; Wang, S.; Cui, X.; Jing, J.; Yu, L.; Xue, B.; Shi, H. Adipocyte Utx deficiency promotes high-fat diet-induced metabolic dysfunction in mice. Cells, 2022, 11(2), 181.
[http://dx.doi.org/10.3390/cells11020181] [PMID: 35053297]
[70]
Chen, H.; Liu, C.; Wang, Q.; Xiong, M.; Zeng, X.; Yang, D.; Xie, Y.; Su, H.; Zhang, Y.; Huang, Y.; Chen, Y.; Yue, J.; Liu, C.; Wang, S.; Huang, K.; Zheng, L. Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver. Nat. Commun., 2022, 13(1), 3835.
[http://dx.doi.org/10.1038/s41467-022-31476-0] [PMID: 35788583]
[71]
Chen, L.; Zhang, J.; Zou, Y.; Wang, F.; Li, J.; Sun, F.; Luo, X.; Zhang, M.; Guo, Y.; Yu, Q.; Yang, P.; Zhou, Q.; Chen, Z.; Zhang, H.; Gong, Q.; Zhao, J.; Eizirik, D.L.; Zhou, Z.; Xiong, F.; Zhang, S.; Wang, C.Y. Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus. Cell Death Differ., 2021, 28(6), 1880-1899.
[http://dx.doi.org/10.1038/s41418-020-00714-7] [PMID: 33462408]
[72]
Asif, S.; Morrow, N.M.; Mulvihill, E.E.; Kim, K.H. Understanding dietary intervention-mediated epigenetic modifications in metabolic diseases. Front. Genet., 2020, 11, 590369.
[http://dx.doi.org/10.3389/fgene.2020.590369] [PMID: 33193730]
[73]
Pascale, R.M.; Simile, M.M.; Calvisi, D.F.; Feo, C.F.; Feo, F. S-Adenosylmethionine: From the discovery of its inhibition of tumorigenesis to its use as a therapeutic agent. Cells, 2022, 11(3), 409.
[http://dx.doi.org/10.3390/cells11030409] [PMID: 35159219]
[74]
Wang, Z.; Yao, T.; Pini, M.; Zhou, Z.; Fantuzzi, G.; Song, Z. Betaine improved adipose tissue function in mice fed a high-fat diet: A mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease. Am. J. Physiol. Gastrointest. Liver Physiol., 2010, 298(5), G634-G642.
[http://dx.doi.org/10.1152/ajpgi.00249.2009] [PMID: 20203061]
[75]
Cai, D.; Wang, J.; Jia, Y.; Liu, H.; Yuan, M.; Dong, H.; Zhao, R. Gestational dietary betaine supplementation suppresses hepatic expression of lipogenic genes in neonatal piglets through epigenetic and glucocorticoid receptor-dependent mechanisms. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2016, 1861(1), 41-50.
[http://dx.doi.org/10.1016/j.bbalip.2015.10.002] [PMID: 26494244]
[76]
Guerrerio, A.L.; Colvin, R.M.; Schwartz, A.K.; Molleston, J.P.; Murray, K.F.; Diehl, A.; Mohan, P.; Schwimmer, J.B.; Lavine, J.E.; Torbenson, M.S.; Scheimann, A.O. Choline intake in a large cohort of patients with nonalcoholic fatty liver disease. Am. J. Clin. Nutr., 2012, 95(4), 892-900.
[http://dx.doi.org/10.3945/ajcn.111.020156] [PMID: 22338037]
[77]
Wang, S.; Lin, Y.; Gao, L.; Yang, Z.; Lin, J.; Ren, S.; Li, F.; Chen, J.; Wang, Z.; Dong, Z.; Sun, P.; Wu, B. PPAR-γ integrates obesity and adipocyte clock through epigenetic regulation of Bmal1. Theranostics, 2022, 12(4), 1589-1606.
[http://dx.doi.org/10.7150/thno.69054] [PMID: 35198059]
[78]
Kraus, D.; Yang, Q.; Kong, D.; Banks, A.S.; Zhang, L.; Rodgers, J.T.; Pirinen, E.; Pulinilkunnil, T.C.; Gong, F.; Wang, Y.; Cen, Y.; Sauve, A.A.; Asara, J.M.; Peroni, O.D.; Monia, B.P.; Bhanot, S.; Alhonen, L.; Puigserver, P.; Kahn, B.B. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature, 2014, 508(7495), 258-262.
[http://dx.doi.org/10.1038/nature13198] [PMID: 24717514]
[79]
Pogribny, I.P.; Tryndyak, V.P.; Bagnyukova, T.V.; Melnyk, S.; Montgomery, B.; Ross, S.A.; Latendresse, J.R.; Rusyn, I.; Beland, F.A. Hepatic epigenetic phenotype predetermines individual susceptibility to hepatic steatosis in mice fed a lipogenic methyl-deficient diet. J. Hepatol., 2009, 51(1), 176-186.
[http://dx.doi.org/10.1016/j.jhep.2009.03.021] [PMID: 19450891]
[80]
Martínez-Chantar, M.L.; Vázquez-Chantada, M.; Ariz, U.; Martínez, N.; Varela, M.; Luka, Z.; Capdevila, A.; Rodríguez, J.; Aransay, A.M.; Matthiesen, R.; Yang, H.; Calvisi, D.F.; Esteller, M.; Fraga, M.; Lu, S.C.; Wagner, C.; Mato, J.M. Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology, 2008, 47(4), 1191-1199.
[http://dx.doi.org/10.1002/hep.22159] [PMID: 18318442]
[81]
Strakovsky, R.S.; Wang, H.; Engeseth, N.J.; Flaws, J.A.; Helferich, W.G.; Pan, Y.X.; Lezmi, S. Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis. Toxicol. Appl. Pharmacol., 2015, 284(2), 101-112.
[http://dx.doi.org/10.1016/j.taap.2015.02.021] [PMID: 25748669]
[82]
Ramon-Krauel, M; Pentinat, T; Bloks, VW; Cebrià, J; Ribo, S; Pérez-Wienese, R Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance. Faseb j., 2018, 2018, fj201700717RR..
[http://dx.doi.org/10.1096/fj.201700717RR]
[83]
Li, J.; Huang, J.; Li, J.S.; Chen, H.; Huang, K.; Zheng, L. Accumulation of endoplasmic reticulum stress and lipogenesis in the liver through generational effects of high fat diets. J. Hepatol., 2012, 56(4), 900-907.
[http://dx.doi.org/10.1016/j.jhep.2011.10.018] [PMID: 22173165]
[84]
Zhang, X.; Zhou, D.; Strakovsky, R.; Zhang, Y.; Pan, Y.X. Hepatic cellular senescence pathway genes are induced through histone modifications in a diet-induced obese rat model. Am. J. Physiol. Gastrointest. Liver Physiol., 2012, 302(5), G558-G564.
[http://dx.doi.org/10.1152/ajpgi.00032.2011] [PMID: 22194422]
[85]
Zhang, X.; Xu, G.B.; Zhou, D.; Pan, Y.X. High-fat diet modifies expression of hepatic cellular senescence gene p16(INK4a) through chromatin modifications in adult male rats. Genes Nutr., 2018, 13(1), 6.
[http://dx.doi.org/10.1186/s12263-018-0595-5] [PMID: 29564021]
[86]
Attig, L.; Vigé, A.; Gabory, A.; Karimi, M.; Beauger, A.; Gross, M.S.; Athias, A.; Gallou-Kabani, C.; Gambert, P.; Ekstrom, T.J.; Jais, J.P.; Junien, C. Dietary alleviation of maternal obesity and diabetes: increased resistance to diet-induced obesity transcriptional and epigenetic signatures. PLoS One, 2013, 8(6), e66816.
[http://dx.doi.org/10.1371/journal.pone.0066816] [PMID: 23826145]
[87]
Suzuki, T.; Muramatsu, T.; Morioka, K.; Goda, T.; Mochizuki, K. ChREBP binding and histone modifications modulate hepatic expression of the Fasn gene in a metabolic syndrome rat model. Nutrition, 2015, 31(6), 877-883.
[http://dx.doi.org/10.1016/j.nut.2015.01.005] [PMID: 25933497]
[88]
Du, X.; Cai, C.; Yao, J.; Zhou, Y.; Yu, H.; Shen, W. Histone modifications in FASN modulated by sterol regulatory element-binding protein 1c and carbohydrate responsive-element binding protein under insulin stimulation are related to NAFLD. Biochem. Biophys. Res. Commun., 2017, 483(1), 409-417.
[http://dx.doi.org/10.1016/j.bbrc.2016.12.129] [PMID: 28027934]
[89]
Bayoumi, A.; Grønbæk, H.; George, J.; Eslam, M. The epigenetic drug discovery landscape for metabolic-associated fatty liver disease. Trends Genet., 2020, 36(6), 429-441.
[http://dx.doi.org/10.1016/j.tig.2020.03.003] [PMID: 32396836]
[90]
Wang, Q.; Jiang, Y.; Luo, X.; Wang, C.; Wang, N.; He, H.; Zhang, T.; Chen, L. Chitooligosaccharides modulate glucose-lipid metabolism by suppressing smyd3 pathways and regulating gut microflora. Mar. Drugs, 2020, 18(1), 69.
[http://dx.doi.org/10.3390/md18010069] [PMID: 31968646]
[91]
Dai, L.; Lu, S.; Shen, T.; Li, Y.; Chen, J. Methyltransferase SETD2 mediates hepatoprotection of berberine against steatosis. Ann. Transl. Med., 2022, 10(10), 552.
[http://dx.doi.org/10.21037/atm-22-1753] [PMID: 35722423]
[92]
Zeybel, M.; Luli, S.; Sabater, L.; Hardy, T.; Oakley, F.; Leslie, J.; Page, A.; Moran Salvador, E.; Sharkey, V.; Tsukamoto, H.; Chu, D.C.K.; Singh, U.S.; Ponzoni, M.; Perri, P.; Di Paolo, D.; Mendivil, E.J.; Mann, J.; Mann, D.A. A proof-of-concept for epigenetic therapy of tissue fibrosis: Inhibition of liver fibrosis progression by 3-deazaneplanocin A. Mol. Ther., 2017, 25(1), 218-231.
[http://dx.doi.org/10.1016/j.ymthe.2016.10.004] [PMID: 28129116]

Rights & Permissions Print Cite
Article Metrics
54
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy