Evaluating the therapeutic potential of one-carbon donors in nonalcoholic fatty liver disease

Defect in one-carbon metabolism is one of the multiple underlying pathological pathways contributing to NAFLD pathogenesis. Hence, our study was designed to examine whether different one-carbon donors; betaine, choline, and folic acid would possess beneficial effects in NAFLD treatment. Rats were fed with high fat diet and NAFLD rats were orally treated with different doses of betaine or choline or folic acid for 28 days. All used one-carbon donors had dose-dependent ameliorating effects on NAFLD as they succeeded to reduce body and relative liver weights, serum lipids and liver enzymes. These were accompanied by decreasing hepatic fat accumulation and amending hepatic histological structure. They also improved serum and hepatic redox systems (total glutathione (tGSH), reduced GSH, oxidized GSSG, and GSH/GSSG ratio), hepatic S-adenosylmethionine/S-adenosyl homocysteine (SAM/SAH) ratio and increased hepatic global DNA methylation. There were some discrepancies in the dose and the extent of their effect, where folic acid showed the most prominent effects that could be mediated through the significant surge in hepatic SAM/SAH ratio and better efficient correction of one-carbon metabolism than the other donors. Thus, one-carbon donors can be strongly considered in NAFLD management and might influence the whole therapeutic approaches of fatty liver diseases.