TY - JOUR AU - Liu Shuang AU - Liu Man AU - Zhang Meng-lin AU - Wang Cui-zhe AU - Zhang Yin-liang AU - Zhang Yu-jie AU - Du Chun-yuan AU - Sheng Su-fang AU - Wang Wei AU - Fan Ya-tong AU - Song Jia-ni AU - Huang Jin-can AU - Feng Yue-yao AU - Qiao Wei AU - Huang Jin-long AU - Li Yu-hui AU - Zhou Lu AU - Zhang Jun AU - Chang Yong-sheng PY - 2022 TI - Transcription factor Klf9 controls bile acid reabsorption and enterohepatic circulation in mice via promoting intestinal Asbt expression JF - Acta Pharmacologica Sinica; Vol 43, No 9 (September 2022): Acta Pharmacologica Sinica Y2 - 2022 KW - N2 - 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 (Klf9 vil−/− ) mice. In contrast, BA levels in the gallbladder and faeces were reduced, whereas BA levels in the serum were increased in intestinal Klf9 transgenic (Klf9 Rosa26+/+ ) 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. UR - http://www.chinaphar.com/article/view/10667