Proceedings of the International scientific and practical conference ―New York Global Science Conference 2026‖ (March 6-8, 2026) / Publisher website: www.naukainfo.com. – New York, USA, 2026. - 250 p.

201 Evidence from experimental studies using inbred laboratory mouse strains (C57BL/6J and DBA/2J) fed a methyl-deficient, adipose-derived diet demonstrated the development of phenotypic features characteristic of metabolic dysfunction- associated steatohepatitis (MASH). These alterations were accompanied by changes in histone methylation patterns, particularly at lysine 9 and lysine 27 of histone H3 as well as lysine 20 of histone H4, highlighting the critical contribution of histone methylation to both the initiation and progression of MASH [4]. According to Schuster S., histone methylation influences not only the acute molecular and physiological processes underlying the transition from simple hepatic steatosis to MASH but also modulates key mechanisms involved in hepatic inflammation. These include hepatocellular lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, and other pathogenic pathways implicated in MASLD development [5]. In addition to methylation, histone demethylation has also been implicated in the pathogenesis of MASLD. Experimental findings indicate that overexpression of lysine demethylase 7A can remove the repressive epigenetic marks H3K9me2 and H3K27me2 from the promoter region of the diacylglycerol O-acyltransferase 2 (DGAT2) gene. This epigenetic modification enhances DGAT2 transcription, leading to increased triglyceride synthesis and accumulation within hepatocytes, ultimately promoting hepatic steatosis. Given that stearoyl-CoA desaturase 1 and DGAT2 are considered promising therapeutic targets and are currently under investigation in clinical trials, regulators of histone methylation such as PHD finger protein 2 and KDM7A may represent potential epigenetic targets for future MASLD therapies [6]. Several studies have indicated that histone acetylation may represent a promising therapeutic target in MASLD. The biologically active phosphorylated metabolite of FTY720 (fingolimod), a prodrug widely used in the treatment of multiple sclerosis, has been shown to attenuate the expression of fatty acid synthase through modulation of histone acetylation. In experimental models of diet-induced MASLD in mice, this mechanism was associated with reduced ceramide synthesis and a decrease in hepatic lipid accumulation [7].