Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing 210095, China.
Department of Medical Cell Biology, Uppsala University, Uppsala SE-75123, Sweden.
Nutrients. 2016 Oct 18;8(10):646. doi: 10.3390/nu8100646.
Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets. This was associated with the significantly elevated serum betaine and methionine levels and hepatic -adenosylmethionine (SAM) and -adenosylhomocysteine (SAH) content. Concurrently, the hepatic nuclear transcription factor liver X receptor LXR was downregulated along with activated signal protein AMP-activated protein kinase (AMPK). Moreover, a chromatin immunoprecipitation assay showed lower LXR binding on CYP7a1 gene promoter and more enriched activation histone marker H3K4me3 on LDLR and SR-BI promoters. These results suggest that gestational and lactational betaine supplementation modulates hepatic gene expression involved in cholesterol metabolism via an AMPK/LXR pathway and histone modification in the weaning offspring.
甜菜碱作为一种动物和人类营养物质，其在葡萄糖和脂质代谢调节中的作用已经得到了广泛的研究，但潜在的机制仍不清楚。在这项研究中，在妊娠和哺乳期给母猪喂食添加甜菜碱的饲料，增加了断奶仔猪肝脏中的胆固醇含量和低密度脂蛋白受体 (LDLR) 和清道夫受体 B 型 I 类 (SR-BI) 基因的表达，但降低了胆汁酸含量和胆固醇-7a-羟化酶 (CYP7a1) 的表达。这与血清甜菜碱和蛋氨酸水平的显著升高以及肝 -腺苷甲硫氨酸 (SAM) 和 -腺苷同型半胱氨酸 (SAH) 含量有关。同时，肝核转录因子肝 X 受体 LXR 下调，同时激活信号蛋白 AMP 激活的蛋白激酶 (AMPK)。此外，染色质免疫沉淀试验显示 CYP7a1 基因启动子上的 LXR 结合减少，LDLR 和 SR-BI 启动子上的激活组蛋白标记 H3K4me3 更丰富。这些结果表明，妊娠期和哺乳期补充甜菜碱通过 AMPK/LXR 途径和组蛋白修饰调节参与胆固醇代谢的肝基因表达。
