肝肠循环
胆汁酸
内科学
小肠
重吸收
共转运蛋白
平衡
回肠
胆固醇7α羟化酶
内分泌学
转录因子
胆盐出口泵
生物
运输机
化学
生物化学
医学
基因
肾
作者
Shuang Liu,Man Liu,Meng-Lin Zhang,Cuizhe Wang,Yinliang Zhang,Chun-Yuan Du,Sufang Sheng,Wei Wang,Yatong Fan,Jiani Song,Jincan Huang,Yue-Yao Feng,Wei Qiao,Yuhui Li,Lu Zhou,Jun Zhang,Yongsheng Chang
标识
DOI:10.1038/s41401-021-00850-x
摘要
Bile acid (BA) homeostasis is regulated by the extensive cross-talk between liver and intestine. Many bile-acid-activated signaling pathways have become attractive therapeutic targets for the treatment of metabolic disorders. In this study we investigated the regulatory mechanisms of BA in the intestine. We showed that the BA levels in the gallbladder and faeces were significantly increased, whereas serum BA levels decreased in systemic Krüppel-like factor 9 (Klf9) deficiency (Klf9−/−) mice. These phenotypes were also observed in the intestine-specific Klf9-deleted (Klf9vil−/−) mice. In contrast, BA levels in the gallbladder and faeces were reduced, whereas BA levels in the serum were increased in intestinal Klf9 transgenic (Klf9Rosa26+/+) mice. By using a combination of biochemical, molecular and functional assays, we revealed that Klf9 promoted the expression of apical sodium-dependent bile acid transporter (Asbt) in the terminal ileum to enhance BA absorption in the intestine. Reabsorbed BA affected liver BA synthetic enzymes by regulating Fgf15 expression. This study has identified a previously neglected transcriptional pathway that regulates BA homeostasis.
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