The Institute of Biochemistry Food and Nutrition Science, The Robert H. Smith Faculty of Agriculture Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Institute of Metabolic Disease, Baylor Scott and White Research Institute, Dallas, Texas, USA.
FASEB J. 2019 Aug;33(8):9334-9349. doi: 10.1096/fj.201802683R. Epub 2019 May 23.
Methyl-donor deficiency is a risk factor for neurodegenerative diseases. Dietary deficiency of the methyl-donors methionine and choline [methionine-choline-deficient (MCD) diet] is a well-established model of nonalcoholic steatohepatitis (NASH), yet brain metabolism has not been studied in this model. We hypothesized that supplemental betaine would protect both the liver and brain in this model and that any benefit to the brain would be due to improved liver metabolism because betaine is a methyl-donor in liver methylation but is not metabolically active in the brain. We fed male Sprague-Dawley rats a control diet, MCD diet, or betaine-supplemented MCD (MCD+B) diet for 8 wk and collected blood and tissue. As expected, betaine prevented MCD diet-induced NASH. However, contrary to our prediction, it did not appear to do so by stimulating methylation; the MCD+B diet worsened hyperhomocysteinemia and depressed liver methylation potential 8-fold compared with the MCD diet. Instead, it significantly increased the expression of genes involved in β-oxidation: fibroblast growth factor 21 and peroxisome proliferator-activated receptor α. In contrast to that of the liver, brain methylation potential was unaffected by diet. Nevertheless, several phospholipid (PL) subclasses involved in stabilizing brain membranes were decreased by the MCD diet, and these improved modestly with betaine. The protective effect of betaine is likely due to the stimulation of β-oxidation in liver and the effects on PL metabolism in brain.-Abu Ahmad, N., Raizman, M., Weizmann, N., Wasek, B., Arning, E., Bottiglieri, T., Tirosh, O., Troen, A. M. Betaine attenuates pathology by stimulating lipid oxidation in liver and regulating phospholipid metabolism in brain of methionine-choline-deficient rats.
甲基供体缺乏是神经退行性疾病的一个风险因素。甲硫氨酸和胆碱的饮食缺乏（甲硫氨酸-胆碱缺乏（MCD）饮食）是一种公认的非酒精性脂肪性肝炎（NASH）模型，但尚未在该模型中研究大脑代谢。我们假设在该模型中补充甜菜碱可以保护肝脏和大脑，并且对大脑的任何益处都将归因于改善肝脏代谢，因为甜菜碱是肝脏甲基化中的甲基供体，但在大脑中没有代谢活性。我们用对照饮食、MCD 饮食或补充甜菜碱的 MCD（MCD+B）饮食喂养雄性 Sprague-Dawley 大鼠 8 周，并收集血液和组织。正如预期的那样，甜菜碱可预防 MCD 饮食诱导的 NASH。然而，与我们的预测相反，它似乎并没有通过刺激甲基化来实现这一目标；与 MCD 饮食相比，MCD+B 饮食使高同型半胱氨酸血症恶化并使肝脏甲基化潜能降低 8 倍。相反，它显着增加了参与β-氧化的基因的表达：成纤维细胞生长因子 21 和过氧化物酶体增殖物激活受体α。与肝脏的情况相反，饮食对大脑甲基化潜能没有影响。尽管如此，几种涉及稳定脑膜的磷脂（PL）亚类因 MCD 饮食而减少，而甜菜碱则适度改善。甜菜碱的保护作用可能归因于肝脏中β-氧化的刺激以及对脑 PL 代谢的影响。-Abu Ahmad，N.，Raizman，M.，Weizmann，N.，Wasek，B.，Arning，E.，Bottiglieri，T.，Tirosh，O.，Troen，A.M. 甜菜碱通过刺激肝脏中的脂质氧化和调节 MCD 大鼠的磷脂代谢来减轻病理。
