Deminice Rafael, da Silva Robin P, Lamarre Simon G, Kelly Karen B, Jacobs René L, Brosnan Margaret E, Brosnan John T
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada,
Amino Acids. 2015 Apr;47(4):839-46. doi: 10.1007/s00726-014-1913-x. Epub 2015 Jan 11.
The purpose of this study was to examine the effects of betaine supplementation on the regulation of one-carbon metabolism and liver lipid accumulation induced by a high-fat diet in rats. Rats were fed one of three different liquid diets: control diet, high-fat diet and high-fat diet supplemented with betaine. The control and high-fat liquid diets contained, respectively, 35 and 71 % of energy derived from fat. Betaine supplementation involved the addition of 1 % (g/L) to the diet. After three weeks on the high-fat diet the rats had increased total liver fat concentration, liver triglycerides, liver TBARS and plasma TNF-α. The high-fat diet decreased the hepatic S-adenosylmethionine concentration and the S-adenosylmethionine/S-adenosylhomocysteine ratio compared to the control as well as altering the expression of genes involved in one-carbon metabolism. Betaine supplementation substantially increased the hepatic S-adenosylmethionine concentration (~fourfold) and prevented fatty liver and hepatic injury induced by the high-fat diet. It was accompanied by the normalization of the gene expression of BHMT, GNMT and MGAT, which code for key enzymes of one-carbon metabolism related to liver fat accumulation. In conclusion, the regulation of the expression of MGAT by betaine supplementation provides an additional and novel mechanism by which betaine supplementation regulates lipid metabolism and prevents accumulation of fat in the liver.
本研究的目的是探讨补充甜菜碱对高脂饮食诱导的大鼠一碳代谢调节及肝脏脂质蓄积的影响。大鼠喂食三种不同的液体饮食之一：对照饮食、高脂饮食和补充甜菜碱的高脂饮食。对照和高脂液体饮食分别含有35%和71%来自脂肪的能量。补充甜菜碱是在饮食中添加1%（g/L）。高脂饮食喂养三周后，大鼠肝脏总脂肪浓度、肝脏甘油三酯、肝脏丙二醛和血浆肿瘤坏死因子-α升高。与对照相比，高脂饮食降低了肝脏S-腺苷甲硫氨酸浓度和S-腺苷甲硫氨酸/S-腺苷同型半胱氨酸比值，并改变了参与一碳代谢的基因表达。补充甜菜碱显著增加了肝脏S-腺苷甲硫氨酸浓度（约四倍），并预防了高脂饮食诱导的脂肪肝和肝损伤。这伴随着甜菜碱同型半胱氨酸甲基转移酶（BHMT）、甘氨酸N-甲基转移酶（GNMT）和单酰甘油酰基转移酶（MGAT）基因表达的正常化，这些基因编码与肝脏脂肪蓄积相关的一碳代谢关键酶。总之，补充甜菜碱对MGAT表达的调节提供了一种额外的新机制，通过该机制补充甜菜碱可调节脂质代谢并防止脂肪在肝脏中蓄积。
