Besnard Philippe, Landrier Jean-François, Grober Jacques, Niot Isabelle
Laboratoire de physiologie de la nutrition, Ecole nationale supérieure de biologie appliquée à la nutrition et à l'alimentation (ENSBANA), UMR 5170-CESG Cnrs/INRA/Université de Bourgogne, 1, esplanade Erasme, 21000 Dijon, France.
Med Sci (Paris). 2004 Jan;20(1):73-7. doi: 10.1051/medsci/200420173.
In the body, cholesterol balance results from an equilibrium between supplies (diet and cellular de novo synthesis), and losses (cellular use and elimination in feces, essentially as bile acids). Bile acids are synthesized from cholesterol in the liver. After conjugation to glycine or taurine, bile acids are secreted with bile in the intestinal lumen where they actively participate to the digestion and absorption of dietary fat and lipid-soluble vitamins. In healthy subjects, more than 95% of bile acids are reabsorbed throughout the small intestine and returned by the portal vein to the liver, where they are secreted again into bile. This enterohepatic circulation is essential for maintenance of bile acids balance, and hence, for cholesterol homeostasis. Indeed, the bile acids not reclaimed by intestinal absorption constitute the main physiological way to eliminate a cholesterol excess. Little is known about the molecular mechanisms controlling bile acids reabsorption by the small intestine. The intestinal bile acids uptake mainly takes place through an active transport located in the distal part of the small intestine. To date, four unrelated proteins exhibiting a high affinity for bile acids have been identified in the ileum, and only one, the ileal bile acid-binding protein (I-BABP) is a soluble protein. Therefore, it is thought to be essential for efficient bile acids desorption from the apical plasma membrane, as well as for bile acids intracellular trafficking and targeting towards the basolateral membrane. If this assumption is correct, the I-BABP expression level might be rate limiting for the enterohepatic bile acids circulation, and hence, for cholesterol homeostasis. It was found that both bile acids and cholesterol, probably via oxysterols, are able to up-regulate the transcription rate of I-BABP gene. The fact that intracellular sterol sensors (FXR, LXR, and SREBP1c) are involved in the control of the I-BABP gene expression strongly suggests that I-BABP exerts an important role in maintenance of cholesterol balance.
在体内，胆固醇平衡源于供应（饮食和细胞从头合成）与损失（细胞利用和粪便排泄，主要以胆汁酸形式）之间的平衡。胆汁酸在肝脏中由胆固醇合成。与甘氨酸或牛磺酸结合后，胆汁酸随胆汁分泌到肠腔，在那里它们积极参与膳食脂肪和脂溶性维生素的消化和吸收。在健康受试者中，超过95%的胆汁酸在整个小肠被重吸收，并通过门静脉返回肝脏，在那里它们再次分泌到胆汁中。这种肠肝循环对于维持胆汁酸平衡至关重要，因此对于胆固醇稳态也至关重要。事实上，未被肠道吸收回收的胆汁酸是消除过量胆固醇的主要生理途径。关于控制小肠胆汁酸重吸收的分子机制知之甚少。肠道胆汁酸摄取主要通过位于小肠远端的主动转运进行。迄今为止，在回肠中已鉴定出四种与胆汁酸具有高亲和力的不相关蛋白质，其中只有一种，即回肠胆汁酸结合蛋白（I-BABP）是一种可溶性蛋白质。因此，它被认为对于胆汁酸从顶端质膜的有效解吸附以及胆汁酸的细胞内运输和靶向基底外侧膜至关重要。如果这一假设正确，I-BABP的表达水平可能是肠肝胆汁酸循环的限速因素，因此对于胆固醇稳态也是如此。研究发现，胆汁酸和胆固醇可能通过氧甾醇能够上调I-BABP基因的转录速率。细胞内固醇传感器（FXR、LXR和SREBP1c）参与I-BABP基因表达的控制这一事实强烈表明，I-BABP在维持胆固醇平衡中发挥着重要作用。
