A Diet-Sensitive BAF60a-Mediated Pathway Links Hepatic Bile Acid Metabolism to Cholesterol Absorption and Atherosclerosis.
A Diet-Sensitive BAF60a-Mediated Pathway Links Hepatic Bile Acid Metabolism to Cholesterol Absorption and Atherosclerosis.
复制标题
饮食敏感的BAF60A介导的途径将肝胆酸代谢与胆固醇吸收和动脉粥样硬化联系起来。
DOI：
10.1016/j.celrep.2015.10.033
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发表时间：
2015-11-24
期刊：
影响因子：
8.8
通讯作者：
Lin JD
中科院分区：
文献类型：
--
作者：
Meng ZX;Wang L;Chang L;Sun J;Bao J;Li Y;Chen YE;Lin JD
饮食营养素与基因网络相互作用，在代谢应激期间协调适应反应。在这里，我们确定Baf60a是小鼠肝脏中SWI/SNF染色质重塑复合体的一个饮食敏感亚单位，它将高脂肪和高胆固醇饮食的消费与血浆胆固醇水平升高联系起来。用西式饮食喂养后，Baf60a在肝脏中的表达增加。Baf60a的肝细胞特异性失活减少了胆汁酸的产生和胆固醇的吸收，并减轻了饮食诱导的高胆固醇血症和动脉粥样硬化。Baf60a通过CAR/Baf60a前馈调控环刺激胆汁酸合成、修饰和转运相关基因的表达。Baf60a是重新招募SWI/SNF染色质重塑复合体所必需的，以促进靶基因上激活的表观遗传开关。这些研究阐明了西方饮食消费对高脂血症和动脉粥样硬化的调节作用。
Dietary nutrients interact with gene networks to orchestrate adaptive responses during metabolic stress. Here we identify Baf60a as a diet-sensitive subunit of the SWI/SNF chromatin-remodeling complexes in the mouse liver that links the consumption of fat- and cholesterol-rich diet to elevated plasma cholesterol levels. Baf60a expression was elevated in the liver following feeding with a western diet. Hepatocyte-specific inactivation of Baf60a reduced bile acid production and cholesterol absorption, and attenuated diet-induced hypercholesterolemia and atherosclerosis in mice. Baf60a stimulates expression of genes involved in bile acid synthesis, modification, and transport through a CAR/Baf60a feedforward regulatory loop. Baf60a is required for the recruitment of the SWI/SNF chromatin-remodeling complexes to facilitate an activating epigenetic switch on target genes. These studies elucidate a regulatory pathway that mediates the hyperlipidemic and atherogenic effects of western diet consumption.