Evaluating the therapeutic potential of one-carbon donors in nonalcoholic fatty liver disease
Evaluating the therapeutic potential of one-carbon donors in nonalcoholic fatty liver disease
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DOI：
10.1016/j.ejphar.2019.01.039
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发表时间：
2019-03-15
影响因子：
5
通讯作者：
Kamel, Maher A.
中科院分区：
文献类型：
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作者：
Bakir, Marwa B.;Salama, Mona A.;Kamel, Maher A.
一碳代谢缺陷是导致NAFLD发病的多种潜在病理途径之一。因此，我们的研究旨在检查不同的一碳供体;甜菜碱，胆碱和叶酸是否在NAFLD治疗中具有有益作用。采用高脂饲料喂养大鼠，并分别给予不同剂量的甜菜碱、胆碱或叶酸治疗NAFLD大鼠28天。所有使用的一碳供体对NAFLD具有剂量依赖性的改善作用，因为它们成功地降低了体重和相对肝脏重量、血脂和肝酶。这些都伴随着减少肝脏脂肪堆积和改善肝脏组织结构。它们还改善了血清和肝脏氧化还原系统（总谷胱甘肽（tGSH）、还原型GSH、氧化型GSSG和GSH/GSSG比值）、肝脏S-腺苷甲硫氨酸/S-腺苷高半胱氨酸（SAM/SAH）比值，并增加了肝脏整体DNA甲基化。在剂量和其作用程度方面存在一些差异，其中叶酸显示出最突出的作用，其可以通过肝脏SAM/SAH比率的显著激增和比其他供体更有效地校正一碳代谢来介导。因此，一碳供体可以在NAFLD管理中被强烈考虑，并可能影响脂肪肝疾病的整个治疗方法。
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.