Wang Xinfang, Shao Yu, Yang Zhi, Yang Haiming, Wang Zhiyue
College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
Animals (Basel). 2025 Mar 3;15(5):719. doi: 10.3390/ani15050719.
This study aimed to investigate the mediating effect of vanin-1 (VNN1) and its DNA methylation on the reduction in liver fat synthesis due to the role of betaine and 5-Azacytidine (5-AZA) in geese. Twenty-eight 35-day-old male Jiangnan white geese with similar body weight (BW) and good health conditions were randomized into four groups (seven birds per group). All the birds were housed with the same type of basal diet. The control group was treated with normal saline intraperitoneally (I.P.); the AZA group was treated I.P. with AZA (2 mg/kg); the betaine group was fed with betaine through the diet and treated I.P. with normal saline (1.2 g/kg); the AZA+betaine group was fed with betaine through the diet and treated I.P. with AZA. The results showed that the administration of AZA significantly increased serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and VNN1 enzyme activity ( < 0.05); additionally, the expression levels of the molecules in various tissues were up-regulated to different extents, such as VNN1, fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl-CoA dehydrogenase (SCD), and sterol regulatory element binding protein (SREBP); in contrast, the treatment of betaine reduced serum TC levels and the S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) ratio; furthermore, hepatic DNA methylation in the AZA group was decreased in terms of the VNN1 promoter region. The results demonstrated that the expression of the gene was negatively correlated with DNA methylation. This finding verified the key role of and its methylation in the inhibition of liver lipid synthesis by betaine and provided a novel molecular mechanism for the regulation of liver lipid metabolism.
本研究旨在探讨鹅肌醇硫酸酯酶1（VNN1）及其DNA甲基化在甜菜碱和5-氮杂胞苷（5-AZA）对肝脏脂肪合成减少作用中的中介效应。选取28只体重（BW）相近、健康状况良好的35日龄雄性江南白鹅，随机分为四组（每组7只）。所有鹅均饲喂相同类型的基础日粮。对照组腹腔注射（I.P.）生理盐水；AZA组腹腔注射AZA（2 mg/kg）；甜菜碱组通过日粮添加甜菜碱并腹腔注射生理盐水（1.2 g/kg）；AZA+甜菜碱组通过日粮添加甜菜碱并腹腔注射AZA。结果表明，注射AZA显著提高了血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）水平以及VNN1酶活性（<0.05）；此外，各组织中多种分子的表达水平均有不同程度上调，如VNN1、脂肪酸合酶（FAS）、乙酰辅酶A羧化酶（ACC）、硬脂酰辅酶A去饱和酶（SCD）和固醇调节元件结合蛋白（SREBP）；相反，甜菜碱处理降低了血清TC水平以及S-腺苷甲硫氨酸/S-腺苷同型半胱氨酸（SAM/SAH）比值；此外，AZA组VNN1启动子区域的肝脏DNA甲基化水平降低。结果表明，该基因的表达与DNA甲基化呈负相关。这一发现证实了VNN1及其甲基化在甜菜碱抑制肝脏脂质合成中的关键作用，并为肝脏脂质代谢调控提供了新的分子机制。
