Betaine supplementation alleviates corticosterone-induced hepatic cholesterol accumulation through epigenetic modulation of HMGCR and CYP7A1 genes in laying hens.
Betaine supplementation alleviates corticosterone-induced hepatic cholesterol accumulation through epigenetic modulation of HMGCR and CYP7A1 genes in laying hens.
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甜菜碱补充剂通过HMGCR和CYP7A1基因的表观遗传调节抑制皮质酮诱导的产蛋鸡肝脏胆固醇蓄积
DOI：
10.1016/j.psj.2024.103435
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发表时间：
2024-03
期刊：
影响因子：
4.4
通讯作者：
Hu, Yun
中科院分区：
文献类型：
--
作者：
Wu, Yulin;Zhang, Mengwei;Meng, Fanchi;Ren, Kunpeng;Li, Ding;Luo, Xugang;Hu, Yun
过量的皮质酮（corticosterone，CORT）暴露可导致鸡肝脏胆固醇蓄积，母体添加甜菜碱可通过表观遗传修饰降低子代鸡肝脏胆固醇沉积。然而，它仍然不确定是否提供甜菜碱蛋鸡可以保护皮质醇诱导的肝脏胆固醇积累通过表观遗传机制。本研究旨在探讨饲粮甜菜碱对CORT暴露蛋鸡血浆和肝脏胆固醇含量、肝脏胆固醇代谢相关基因表达及其启动子DNA甲基化的影响。选用72只130日龄蛋鸡，随机分为对照组（CON）、CORT组和CORT+甜菜碱组（CORT+BET）。实验持续35 d。CON组和CORT组饲喂基础日粮，CORT+BET组饲喂基础日粮中添加0.1%甜菜碱。CORT组和CORT+BET组在试验第28天每天皮下注射CORT（4.0mg/kg体重），CON组注射等体积的溶剂，共注射7 d。结果表明，CORT给药导致显著增加血浆和肝脏中胆固醇含量显著升高（P < 0.05），与活化有关固醇调节元件结合转录因子2（SREBP 2）、3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）、卵磷脂胆固醇酰基转移酶（LCAT）和低密度脂蛋白受体（LDLR）基因表达的差异有统计学意义（P < 0.05），与对照组相比，甜菜碱能显著抑制肝脏中胆固醇-7-α羟化酶（CYP 7A 1）和甾醇-27-羟化酶（CYP 27 A1）基因的表达，而CORT诱导的HMGCR mRNA和蛋白丰度的上调以及CYP 7A 1 mRNA和蛋白丰度的下调则被甜菜碱完全恢复正常（P < 0.05）。CORT处理后HMGCR基因启动子甲基化水平降低（P < 0.05），CYP 7A 1基因启动子甲基化水平升高（P < 0.05）。甜菜碱可显著减轻CORT诱导的HMGCR和CYP 7A 1基因启动子甲基化状态的改变（P < 0.05）。这些结果表明，日粮中添加甜菜碱通过HMGCR和CYP 7A 1基因的表观遗传调节保护产蛋鸡免受CORT诱导的肝脏胆固醇积累。
Excessive corticosterone (CORT) exposure could cause hepatic cholesterol accumulation in chickens and maternal betaine supplementation could decrease hepatic cholesterol deposition through epigenetic modifications in offspring chickens. Nevertheless, it remains uncertain whether providing betaine to laying hens could protect CORT-induced hepatic cholesterol accumulation via epigenetic mechanisms. This study aimed to examine the effects of dietary betaine on plasma and hepatic cholesterol contents, expression of cholesterol metabolic genes, as well as DNA methylation on their promoters in the liver of laying hens exposed to CORT. A total of 72 laying hens at 130 d of age were randomly divided into 3 groups: control (CON), CORT, and CORT+betaine (CORT+BET) groups. The experiment lasted for 35 d. Chickens in CON and CORT groups were fed a basal diet, whereas the CORT+BET group chickens were fed the basal diet supplemented with 0.1% betaine for 35 d. On d 28 of the experiment, chickens in CORT and CORT+BET groups received daily subcutaneous injections of CORT (4.0 mg/kg body weight), whereas the CON group chickens were injected with an equal volume of solvent for 7 d. The results showed that CORT administration led to a significant increase (P < 0.05) in the contents of cholesterol in plasma and liver, associated with activation (P < 0.05) of sterol regulatory element binding transcription factor 2 (SREBP2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), lecithin-cholesterol acyltransferase (LCAT) and low-density lipoprotein receptor (LDLR) genes expression, and inhibition of cholesterol-7-alpha hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) genes expression in the liver compared to the CON. In contrast, CORT-induced up-regulation of HMGCR mRNA and protein abundances and downregulation of CYP7A1 mRNA and protein abundances were completely normalized (P < 0.05) by betaine supplementation. Besides, CORT injection led to significant hypomethylation (P < 0.05) on HMGCR promoter and hypermethylation (P < 0.05) on CYP7A1 promoter. Moreover, dietary betaine rescued (P < 0.05) CORT-induced changes in methylation status of HMGCR and CYP7A1 genes promoters. These results indicate that dietary betaine addition protects laying hens from CORT-induced hepatic cholesterol accumulation via epigenetic modulation of HMGCR and CYP7A1 genes.
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