The Effect of Methyl Donors in a Murine Model of MASLD in a Multidisciplinary Study.

Addressing the challenge of Metabolic Dysfunction Associated Steatotic Liver Diseases (MASLD), this study assesses the efficacy of methyl donor supplementation in a C57BL/6J mouse model, hypothesizing its potential to mitigate disease symptoms through epigenetic and metabolic pathways. In the liver, global DNA methylation was quantified and the transcriptome was analyzed using dual-channel microarrays. An increased DNA methylation, normalization in the expression of lipid-related genes, and hypermethylation of lipogenic genes were observed in methyl donnors supplemental mice (MET). A model using male C57BL/6J mice was used, divided into three groups: normal diet (ND, n=8), high-fat and high-sugar diet (HF, n=8) for 18 weeks, and a third group with HF diet for 10 weeks followed by 8 weeks of supplementation with methionine, choline, betaine, folate, cobalamin, and ZnSO4 (MET, n=8). At sacrifice, liver samples were collected and processed to obtain DNA, which was then subjected to bisulfite conversion following the manufacturer's protocol (Zymo Research). Subsequently, methylation was evaluated using the Infinum Mouse Methylation BeadChip Array (Illumina) following the manufacturer's instructions