m6A methylation – a new target of metabolic diseases induced by environmental pollutants
-
Runfeng Chang
und Huili Wang
Abstract
Exposure to environmental pollutants is closely associated with the development of obesity and related metabolic diseases. As the most prevalent form of eukaryotic chemical modification, N6-methyladenosine (m6A) methylation regulated by series enzymes plays an important role in the pathogenesis of metabolic diseases such as obesity, non-alcoholic fatty liver disease (NAFLD), atherosclerosis (AS), and type 2 diabetes (T2D). Therefore, investigating the specific mechanisms of m6A methylation in obesity and related metabolic diseases and its relationship with environmental pollutants is vital for developing treatment and prevention strategies. This article summarizes the latest research on m6A methylation in glucose and lipid metabolism-related diseases and elucidates the specific molecular mechanisms of metabolic disorders regulated by m6A methylation-related enzymes. More importantly, we highlight that m6A methylation process is a target for environmental pollutants in inducing human metabolic diseases. Our review aims to provide new insights into understanding the underlying mechanisms of environmental pollutant-induced metabolic diseases and to explore preventive and therapeutic measures.
Award Identifier / Grant number: 21KJB610001
Funding source: Natural Science Foundation of Jiangsu Province
Award Identifier / Grant number: BK20231341
Funding source: Science and Technology Program of Suzhou
Award Identifier / Grant number: SS202150
Funding source: National Natural Science Foundation of China
Award Identifier / Grant number: 22106118
Award Identifier / Grant number: 22306141
Award Identifier / Grant number: 32371705
-
Research ethics: Not applicable.
-
Informed consent: Not applicable.
-
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Use of Large Language Models, AI and Machine Learning Tools: None declared.
-
Conflict of interest: The authors state no conflict of interest.
-
Research funding: This work was jointly supported by the National Natural Science Foundation of China (22106118, 32371705 and 22306141), Natural Science Foundation of Jiangsu Province (BK20231341),Science and Technology Program of Suzhou (SS202150),and Natural Science Research of Jiangsu Higher Education Institutions of China (21KJB610001).
-
Data availability: Not applicable.
References
1. Jung, UJ, Choi, MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 2014;15:6184–223. https://doi.org/10.3390/ijms15046184.Suche in Google Scholar PubMed PubMed Central
2. You, L, Kou, J, Wang, M, Ji, G, Li, X, Su, C, et al.. An exposome atlas of serum reveals the risk of chronic diseases in the Chinese population. Nat Commun 2024;15:2268. https://doi.org/10.1038/s41467-024-46595-z.Suche in Google Scholar PubMed PubMed Central
3. Bowe, B, Xie, Y, Li, T, Yan, Y, Xian, H, Al-Aly, Z. The 2016 global and national burden of diabetes mellitus attributable to PM(2·5) air pollution. Lancet Planet Health 2018;2:e301–12. https://doi.org/10.1016/s2542-5196-18-30140-2.Suche in Google Scholar
4. Shao, W, Pan, B, Li, Z, Peng, R, Yang, W, Xie, Y, et al.. Gut microbiota mediates ambient PM2. 5 exposure-induced abnormal glucose metabolism via short-chain fatty acids. J Hazard Mater 2024;476:135096. https://doi.org/10.1016/j.jhazmat.2024.135096.Suche in Google Scholar PubMed PubMed Central
5. Kang, N, Chen, W, Osazuwa, N, Qiu, C, Botelho, JC, Calafat, AM, et al.. Longitudinal associations of PFAS exposure with insulin sensitivity and β-cell function among hispanic Women with a history of gestational diabetes mellitus. Diabetes Care 2025;48:564–8. https://doi.org/10.2337/dc24-2056.Suche in Google Scholar PubMed PubMed Central
6. Lee, I, Park, YJ, Kim, MJ, Kim, S, Choi, S, Park, J, et al.. Associations of urinary concentrations of phthalate metabolites, bisphenol A, and parabens with obesity and diabetes mellitus in a Korean adult population: Korean National Environmental Health Survey (KoNEHS) 2015-2017. Environ Int 2021;146:106227. https://doi.org/10.1016/j.envint.2020.106227.Suche in Google Scholar PubMed
7. Scinicariello, F, Buser, MC. Urinary polycyclic aromatic hydrocarbons and childhood obesity: NHANES (2001-2006). Environ Health Perspect 2014;122:299–303. https://doi.org/10.1289/ehp.1307234.Suche in Google Scholar PubMed PubMed Central
8. Domazet, SL, Grøntved, A, Timmermann, AG, Nielsen, F, Jensen, TK. Longitudinal associations of exposure to perfluoroalkylated substances in childhood and adolescence and indicators of adiposity and glucose metabolism 6 and 12 years later: the European youth heart study. Diabetes Care 2016;39:1745–51. https://doi.org/10.2337/dc16-0269.Suche in Google Scholar PubMed
9. Tawar, N, Banerjee, BD, Mishra, BK, Sharma, T, Tyagi, S, Madhu, SV, et al.. Adipose tissue levels of DDT as risk factor for obesity and type 2 diabetes mellitus. Indian J Endocrinol Metab 2021;25:160–5. https://doi.org/10.4103/ijem.ijem-198-21.Suche in Google Scholar
10. Arsenescu, V, Arsenescu, RI, King, V, Swanson, H, Cassis, LA. Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis. Environ Health Perspect 2008;116:761–8. https://doi.org/10.1289/ehp.10554.Suche in Google Scholar PubMed PubMed Central
11. Erkin-Cakmak, A, Harley, KG, Chevrier, J, Bradman, A, Kogut, K, Huen, K, et al.. In utero and childhood polybrominated diphenyl ether exposures and body mass at age 7 years: the CHAMACOS study. Environ Health Perspect 2015;123:636–42. https://doi.org/10.1289/ehp.1408417.Suche in Google Scholar PubMed PubMed Central
12. Liu, C, Xu, X, Bai, Y, Wang, TY, Rao, X, Wang, A, et al.. Air pollution-mediated susceptibility to inflammation and insulin resistance: influence of CCR2 pathways in mice. Environ Health Perspect 2014;122:17–26. https://doi.org/10.1289/ehp.1306841.Suche in Google Scholar PubMed PubMed Central
13. Irigaray, P, Ogier, V, Jacquenet, S, Notet, V, Sibille, P, Méjean, L, et al.. Benzo[a]pyrene impairs beta-adrenergic stimulation of adipose tissue lipolysis and causes weight gain in mice. A novel molecular mechanism of toxicity for a common food pollutant. FEBS J 2006;273:1362–72. https://doi.org/10.1111/j.1742-4658.2006.05159.x.Suche in Google Scholar PubMed
14. Wu, H, Yu, W, Meng, F, Mi, J, Peng, J, Liu, J, et al.. Polychlorinated biphenyls-153 induces metabolic dysfunction through activation of ROS/NF-κB signaling via downregulation of HNF1b. Redox Biol 2017;12:300–10. https://doi.org/10.1016/j.redox.2017.02.026.Suche in Google Scholar PubMed PubMed Central
15. Koppel, N, Maini Rekdal, V, Balskus, EP. Chemical transformation of xenobiotics by the human gut microbiota. Science 2017;356. https://doi.org/10.1126/science.aag2770.Suche in Google Scholar PubMed PubMed Central
16. Wang, PX, Deng, XR, Zhang, CH, Yuan, HJ. Gut microbiota and metabolic syndrome. Chin Med J (Engl) 2020;133:808–16. https://doi.org/10.1097/cm9.0000000000000696.Suche in Google Scholar PubMed PubMed Central
17. Zhao, X, Yang, Y, Sun, BF, Shi, Y, Yang, X, Xiao, W, et al.. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res 2014;24:1403–19. https://doi.org/10.1038/cr.2014.151.Suche in Google Scholar PubMed PubMed Central
18. Dong, G, Yu, J, Shan, G, Su, L, Yu, N, Yang, S. N6-Methyladenosine methyltransferase METTL3 promotes angiogenesis and atherosclerosis by upregulating the JAK2/STAT3 pathway via m6A reader IGF2BP1. Front Cell Dev Biol 2021;9:731810. https://doi.org/10.3389/fcell.2021.731810.Suche in Google Scholar PubMed PubMed Central
19. Sun, D, Zhao, T, Zhang, Q, Wu, M, Zhang, Z. Fat mass and obesity-associated protein regulates lipogenesis via m(6) A modification in fatty acid synthase mRNA. Cell Biol Int 2021;45:334–44. https://doi.org/10.1002/cbin.11490.Suche in Google Scholar PubMed
20. Bornaque, F, Delannoy, CP, Courty, E, Rabhi, N, Carney, C, Rolland, L, et al.. Glucose regulates m(6)A methylation of RNA in pancreatic islets. Cells 2022;11. https://doi.org/10.3390/cells11020291.Suche in Google Scholar PubMed PubMed Central
21. Yang, Y, Cai, J, Yang, X, Wang, K, Sun, K, Yang, Z, et al.. Dysregulated m6A modification promotes lipogenesis and development of non-alcoholic fatty liver disease and hepatocellular carcinoma. Mol Ther 2022;30:2342–53. https://doi.org/10.1016/j.ymthe.2022.02.021.Suche in Google Scholar PubMed PubMed Central
22. Zaccara, S, Ries, RJ, Jaffrey, SR. Reading, writing and erasing mRNA methylation. Nat Rev Mol Cell Biol 2019;20:608–24. https://doi.org/10.1038/s41580-019-0168-5.Suche in Google Scholar PubMed
23. Kobayashi, M, Ohsugi, M, Sasako, T, Awazawa, M, Umehara, T, Iwane, A, et al.. The RNA methyltransferase complex of WTAP, METTL3, and METTL14 regulates mitotic clonal expansion in adipogenesis. Mol Cell Biol 2018;38. https://doi.org/10.1128/mcb.00116-18.Suche in Google Scholar PubMed PubMed Central
24. De, JDF, Zhang, Z, Kahraman, S, Brown, NK, Chen, M, Hu, J, et al.. m(6)A mRNA methylation regulates human β-cell biology in physiological states and in type 2 diabetes. Nat Metab 2019;1:765–74. https://doi.org/10.1038/s42255-019-0089-9.Suche in Google Scholar PubMed PubMed Central
25. Xiao, W, Adhikari, S, Dahal, U, Chen, YS, Hao, YJ, Sun, BF, et al.. Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Mol Cell 2016;61:507–19. https://doi.org/10.1016/j.molcel.2016.03.004.Suche in Google Scholar
26. Cai, M, Liu, Q, Jiang, Q, Wu, R, Wang, X, Wang, Y. Loss of m(6) A on FAM134B promotes adipogenesis in porcine adipocytes through m(6) A-YTHDF2-dependent way. IUBMB Life 2019;71:580–6. https://doi.org/10.1002/iub.1974.Suche in Google Scholar PubMed
27. Jiang, Q, Sun, B, Liu, Q, Cai, M, Wu, R, Wang, F, et al.. MTCH2 promotes adipogenesis in intramuscular preadipocytes via an m(6)A-YTHDF1-dependent mechanism. FASEB J 2019;33:2971–81. https://doi.org/10.1096/fj.201801393rrr.Suche in Google Scholar PubMed PubMed Central
28. Roundtree, IA, Luo, GZ, Zhang, Z, Wang, X, Zhou, T, Cui, Y, et al.. YTHDC1 mediates nuclear export of N(6)-methyladenosine methylated mRNAs. Elife 2017;6. https://doi.org/10.7554/elife.31311.Suche in Google Scholar
29. Huang, H, Weng, H, Sun, W, Qin, X, Shi, H, Wu, H, et al.. Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol 2018;20:285–95. https://doi.org/10.1038/s41556-018-0045-z.Suche in Google Scholar PubMed PubMed Central
30. Wu, R, Guo, G, Bi, Z, Liu, Y, Zhao, Y, Chen, N, et al.. m(6)A methylation modulates adipogenesis through JAK2-STAT3-C/EBPβ signaling. Biochim Biophys Acta Gene Regul Mech 2019;1862:796–806. https://doi.org/10.1016/j.bbagrm.2019.06.008.Suche in Google Scholar PubMed
31. Chen, X, Luo, Y, Jia, G, Liu, G, Zhao, H, Huang, Z. FTO promotes adipogenesis through inhibition of the Wnt/β-catenin signaling pathway in porcine intramuscular preadipocytes. Anim Biotechnol 2017;28:268–74. https://doi.org/10.1080/10495398.2016.1273835.Suche in Google Scholar PubMed
32. Labbé, K, Mookerjee, S, Le Vasseur, M, Gibbs, E, Lerner, C, Nunnari, J. The modified mitochondrial outer membrane carrier MTCH2 links mitochondrial fusion to lipogenesis. J Cell Biol 2021;220. https://doi.org/10.1083/jcb.202103122.Suche in Google Scholar PubMed PubMed Central
33. Yao, Y, Bi, Z, Wu, R, Zhao, Y, Liu, Y, Liu, Q, et al.. METTL3 inhibits BMSC adipogenic differentiation by targeting the JAK1/STAT5/C/EBPβ pathway via an m(6)A-YTHDF2-dependent manner. FASEB J 2019;33:7529–44. https://doi.org/10.1096/fj.201802644r.Suche in Google Scholar
34. Song, T, Yang, Y, Wei, H, Xie, X, Lu, J, Zeng, Q, et al.. Zfp217 mediates m6A mRNA methylation to orchestrate transcriptional and post-transcriptional regulation to promote adipogenic differentiation. Nucleic Acids Res 2019;47:6130–44. https://doi.org/10.1093/nar/gkz312.Suche in Google Scholar PubMed PubMed Central
35. Liu, Q, Zhao, Y, Wu, R, Jiang, Q, Cai, M, Bi, Z, et al.. ZFP217 regulates adipogenesis by controlling mitotic clonal expansion in a METTL3-m(6)A dependent manner. RNA Biol 2019;16:1785–93. https://doi.org/10.1080/15476286.2019.1658508.Suche in Google Scholar PubMed PubMed Central
36. Li, Z, Qi, J, Liu, H, Tang, Y, Liu, J, Sun, C. Abnormal m6A modification in non-alcoholic fatty liver disease. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021;46:785–92. https://doi.org/10.11817/j.issn.1672-7347.2021.210264.Suche in Google Scholar PubMed PubMed Central
37. Qin, Y, Li, B, Arumugam, S, Lu, Q, Mankash, SM, Li, J, et al.. m(6)A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Rep 2021;37:109968. https://doi.org/10.1016/j.celrep.2021.109968.Suche in Google Scholar PubMed PubMed Central
38. Peng, Z, Gong, Y, Wang, X, He, W, Wu, L, Zhang, L, et al.. METTL3-m(6)A-Rubicon axis inhibits autophagy in nonalcoholic fatty liver disease. Mol Ther 2022;30:932–46. https://doi.org/10.1016/j.ymthe.2021.09.016.Suche in Google Scholar PubMed PubMed Central
39. Zhong, X, Yu, J, Frazier, K, Weng, X, Li, Y, Cham, CM, et al.. Circadian clock regulation of hepatic lipid metabolism by modulation of m(6)A mRNA methylation. Cell Rep 2018;25:1816–28.e1814. https://doi.org/10.1016/j.celrep.2018.10.068.Suche in Google Scholar PubMed PubMed Central
40. Li, Y, Ma, Z, Jiang, S, Hu, W, Li, T, Di, S, et al.. A global perspective on FOXO1 in lipid metabolism and lipid-related diseases. Prog Lipid Res 2017;66:42–9. https://doi.org/10.1016/j.plipres.2017.04.002.Suche in Google Scholar PubMed
41. Jian, D, Wang, Y, Jian, L, Tang, H, Rao, L, Chen, K, et al.. METTL14 aggravates endothelial inflammation and atherosclerosis by increasing FOXO1 N6-methyladeosine modifications. Theranostics 2020;10:8939–56. https://doi.org/10.7150/thno.45178.Suche in Google Scholar PubMed PubMed Central
42. Yang, Y, Shen, F, Huang, W, Qin, S, Huang, JT, Sergi, C, et al.. Glucose is involved in the dynamic regulation of m6A in patients with type 2 diabetes. J Clin Endocrinol Metab 2019;104:665–73. https://doi.org/10.1210/jc.2018-00619.Suche in Google Scholar PubMed
43. Magnúsdóttir, S, Ravcheev, D, de Crécy-Lagard, V, Thiele, I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Front Genet 2015;6:148. https://doi.org/10.3389/fgene.2015.00148.Suche in Google Scholar PubMed PubMed Central
44. Sun, L, Ma, L, Zhang, H, Cao, Y, Wang, C, Hou, N, et al.. Fto deficiency reduces anxiety- and depression-like behaviors in mice via alterations in gut microbiota. Theranostics 2019;9:721–33. https://doi.org/10.7150/thno.31562.Suche in Google Scholar PubMed PubMed Central
45. Wang, X, Li, Y, Chen, W, Shi, H, Eren, AM, Morozov, A, et al.. Transcriptome-wide reprogramming of N(6)-methyladenosine modification by the mouse microbiome. Cell Res 2019;29:167–70. https://doi.org/10.1038/s41422-018-0127-2.Suche in Google Scholar PubMed PubMed Central
46. Jabs, S, Becavin, C, Nahori, M-A, Guerinau, V, Touboul, D, Ghozlane, A, et al.. A role for gut microbiota in m6A epitranscriptomic mRNA modifications in different host tissues. bioRxiv; 2018.10.1101/504266Suche in Google Scholar
47. Tong, J, Cao, G, Zhang, T, Sefik, E, Amezcua Vesely, MC, Broughton, JP, et al.. m(6)A mRNA methylation sustains Treg suppressive functions. Cell Res 2018;28:253–6. https://doi.org/10.1038/cr.2018.7.Suche in Google Scholar PubMed PubMed Central
48. Zong, X, Zhao, J, Wang, H, Lu, Z, Wang, F, Du, H, et al.. Mettl3 deficiency sustains long-chain fatty acid absorption through suppressing traf6-dependent inflammation response. J Immunol 2019;202:567–78. https://doi.org/10.4049/jimmunol.1801151.Suche in Google Scholar PubMed PubMed Central
49. Chen, S, Zhang, L, Li, M, Zhang, Y, Sun, M, Wang, L, et al.. Fusobacterium nucleatum reduces METTL3-mediated m(6)A modification and contributes to colorectal cancer metastasis. Nat Commun 2022;13:1248. https://doi.org/10.1038/s41467-022-28913-5.Suche in Google Scholar PubMed PubMed Central
50. Liu, D, Hu, L, Yang, Y, Wang, Y, Li, Y, Su, J, et al.. Saccharomyces boulardii alleviates allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner. Immunol Lett 2024;267:106853. https://doi.org/10.1016/j.imlet.2024.106853.Suche in Google Scholar PubMed
51. Su, H, Cheung, H, Lau, HC, Chen, H, Zhang, X, Qin, N, et al.. Crosstalk between gut microbiota and RNA N6-methyladenosine modification in cancer. FEMS Microbiol Rev 2023;47. https://doi.org/10.1093/femsre/fuad036.Suche in Google Scholar PubMed
52. Cayir, A, Barrow, TM, Guo, L, Byun, HM. Exposure to environmental toxicants reduces global N6-methyladenosine RNA methylation and alters expression of RNA methylation modulator genes. Environ Res 2019;175:228–34. https://doi.org/10.1016/j.envres.2019.05.011.Suche in Google Scholar PubMed
53. Ning, J, Du, H, Zhang, Y, Liu, Q, Jiang, T, Pang, Y, et al.. N6-Methyladenosine modification of CDH1 mRNA promotes PM2.5-induced pulmonary fibrosis via mediating epithelial mesenchymal transition. Toxicol Sci 2022;185:143–57. https://doi.org/10.1093/toxsci/kfab133.Suche in Google Scholar PubMed
54. Cheng, C, Wu, Y, Xiao, T, Xue, J, Sun, J, Xia, H, et al.. METTL3-mediated m(6)A modification of ZBTB4 mRNA is involved in the smoking-induced EMT in cancer of the lung. Mol Ther Nucleic Acids 2021;23:487–500. https://doi.org/10.1016/j.omtn.2020.12.001.Suche in Google Scholar PubMed PubMed Central
55. Feng, J, Zhang, P, Chen, K, Huang, P, Liang, X, Dong, J, et al.. Soot nanoparticles promote ferroptosis in dopaminergic neurons via alteration of m6A RNA methylation in Parkinson’s disease. J Hazard Mater 2024;473:134691. https://doi.org/10.1016/j.jhazmat.2024.134691.Suche in Google Scholar PubMed
56. Zhao, TX, Wang, JK, Shen, LJ, Long, CL, Liu, B, Wei, Y, et al.. Increased m6A RNA modification is related to the inhibition of the Nrf2-mediated antioxidant response in di-(2-ethylhexyl) phthalate-induced prepubertal testicular injury. Environ Pollut 2020;259:113911. https://doi.org/10.1016/j.envpol.2020.113911.Suche in Google Scholar PubMed
57. Aluru, N, Karchner, SI. PCB126 exposure revealed alterations in m6A RNA modifications in transcripts associated with AHR activation. Toxicol Sci 2021;179:84–94. https://doi.org/10.1093/toxsci/kfaa158.Suche in Google Scholar PubMed PubMed Central
58. Yang, F, Jin, H, Que, B, Chao, Y, Zhang, H, Ying, X, et al.. Dynamic m(6)A mRNA methylation reveals the role of METTL3-m(6)A-CDCP1 signaling axis in chemical carcinogenesis. Oncogene 2019;38:4755–72. https://doi.org/10.1038/s41388-019-0755-0.Suche in Google Scholar PubMed PubMed Central
59. Li, N, Zhang, D, Cao, S, Qiao, M, Zhang, P, Zhao, Q, et al.. The effects of folic acid on RNA m6A methylation in hippocampus as well as learning and memory ability of rats with acute lead exposure. J Funct Foods 2021;76:104276. https://doi.org/10.1016/j.jff.2020.104276.Suche in Google Scholar
60. Qi, Z, Liu, Y, Yang, H, Yang, X, Wang, H, Liu, B, et al.. Protective role of m(6)A binding protein YTHDC2 on CCNB2 in manganese-induced spermatogenesis dysfunction. Chem Biol Interact 2022;351:109754. https://doi.org/10.1016/j.cbi.2021.109754.Suche in Google Scholar PubMed
61. Qi, Z, Wang, S, Li, J, Wen, Y, Cui, R, Zhang, K, et al.. Protective role of mRNA demethylase FTO on axon guidance molecules of nigro-striatal projection system in manganese-induced parkinsonism. J Hazard Mater 2022;426:128099. https://doi.org/10.1016/j.jhazmat.2021.128099.Suche in Google Scholar PubMed
62. Wu, Z-c, Xu, C, Wang, H, Gao, S, Wu, S, Bao, W. Transcriptome-wide assessment of the m6A methylome of intestinal porcine epithelial cells treated with deoxynivalenol 2020. https://doi.org/10.21203/rs.3.rs-73169/v1.Suche in Google Scholar
63. Wu, K, Jia, S, Zhang, J, Zhang, C, Wang, S, Rajput, SA, et al.. Transcriptomics and flow cytometry reveals the cytotoxicity of aflatoxin B(1) and aflatoxin M(1) in bovine mammary epithelial cells. Ecotoxicol Environ Saf 2021;209:111823. https://doi.org/10.1016/j.ecoenv.2020.111823.Suche in Google Scholar PubMed
64. Wu, J, Gan, Z, Zhuo, R, Zhang, L, Wang, T, Zhong, X. Resveratrol attenuates aflatoxin B(1)-induced ROS formation and increase of m(6)A RNA methylation. Animals (Basel) 2020;10. https://doi.org/10.3390/ani10040677.Suche in Google Scholar PubMed PubMed Central
65. Ghazi, T, Nagiah, S, Chuturgoon, AA. Fusaric acid induces hepatic global m6A RNA methylation and differential expression of m6A regulatory genes in vivo - a pilot study. Epigenetics 2022;17:695–703. https://doi.org/10.1080/15592294.2021.1975937.Suche in Google Scholar PubMed PubMed Central
66. Li, J, Fang, L, Xi, M, Ni, A, Qian, Q, Wang, Z, et al.. Toxic effects of triclosan on hepatic and intestinal lipid accumulation in zebrafish via regulation of m6A-RNA methylation. Aquat Toxicol 2024;269:106884. https://doi.org/10.1016/j.aquatox.2024.106884.Suche in Google Scholar PubMed
67. Arumugam, T, Ghazi, T, Chuturgoon, AA. Fumonisin B(1) alters global m6A RNA methylation and epigenetically regulates Keap1-Nrf2 signaling in human hepatoma (HepG2) cells. Arch Toxicol 2021;95:1367–78. https://doi.org/10.1007/s00204-021-02986-5.Suche in Google Scholar PubMed
68. Jin, C, Wang, C, Zhang, C, Ye, Q, Jin, Y, Shi, L. Imazalil resulted in glucolipid metabolism disturbance and abnormal m(6)A RNA methylation in the liver of dam and offspring mice. Ecotoxicol Environ Saf 2024;271:115963. https://doi.org/10.1016/j.ecoenv.2024.115963.Suche in Google Scholar PubMed
69. Zhang, M, Shi, J, Deng, H. Transcriptome-wide m6A modification mediates cardiotoxicity in mice after chronic exposure to microplastics. Chemosphere 2023;317:137877. https://doi.org/10.1016/j.chemosphere.2023.137877.Suche in Google Scholar PubMed
70. Li, W, Tan, M, Wang, H, Wang, Z, Pang, Y, Yang, R, et al.. METTL3-mediated m6A mRNA modification was involved in cadmium-induced liver injury. Environ Pollut 2023;331:121887. https://doi.org/10.1016/j.envpol.2023.121887.Suche in Google Scholar PubMed
71. Cheng, W, Li, X, Zhou, Y, Yu, H, Xie, Y, Guo, H, et al.. Polystyrene microplastics induce hepatotoxicity and disrupt lipid metabolism in the liver organoids. Sci Total Environ 2022;806:150328. https://doi.org/10.1016/j.scitotenv.2021.150328.Suche in Google Scholar PubMed
72. Li, X, Jing, K, Song, P, Yu, J. Aged polystyrene microplastics exacerbate cadmium-induced hepatotoxicity in zebrafish through gut-liver axis metabolic dysregulation. J Environ Chem Ecotoxicol 2025;7:859–71. https://doi.org/10.1016/j.enceco.2025.05.001.Suche in Google Scholar
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/reveh-2025-0057).
© 2025 Walter de Gruyter GmbH, Berlin/Boston