当前位置： SCI文献检索 > AMERICAN JOURNAL OF SURGERY期刊下所有文献 > The coming of age of our understanding of the enterohepatic circulation of bile salts.

The coming of age of our understanding of the enterohepatic circulation of bile salts.

Abstract：

:Recent advances in molecular biology have greatly accelerated knowledge relating to the significance of the enterohepatic circulation of bile salts. This review highlights the role that both oxysterols and bile salts play as ligands which, when bound to nuclear hormone receptors, activate transcription factors that set into play feed-forward catabolism of cholesterol to bile salts and feedback control of bile acid synthesis. The nuclear hormone receptors, liver X receptor (LXR) and farnesoid X receptor (FXR) both combined as heterodimers with retinoid X receptor and with oxysterols and bile salts, respectively as their ligands, initiate powerful genetic controls over cholesterol and bile acid homeostatic mechanisms. LXR/RXR signals molecular control of feed-forward catabolism of cholesterol to bile acids while FXR/RXR initiates feedback control of bile acid synthesis. An additional nuclear hormone receptor, small heterodimer partner (SHP), is required to inhibit the competence factor, liver receptor homolog-1 to achieve repression of bile acid synthesis in the liver and in so doing SHP autoregulates its own function. Additionally, while bile acid synthesis is repressed, pool size is preserved by the action of FXR/RXR at both hepatic and intestinal levels, which genetically signals enhanced hepatocyte bile salt transport by the bile salt export pump (BSEP) and the ileal bile acid binding protein (IBABP) for ileal reabsorption. During activation of cholesterol catabolism, LXR/RXR enhances reverse cholesterol transport by increasing cholesterol efflux via the ABC-1 transporter from extrahepatic cells. This cholesterol is then taken up by high-density lipoprotein (HDL) and transported back to the liver for further cholesterol catabolism and elimination in bile. The genetic coordination of nuclear hormone receptor function within the territory of the enterohepatic of bile salts allows for normal cholesterol and bile acid homeostasis thereby preventing atherosclerosis.

journal_name

Am J Surg

journal_title

American journal of surgery

authors

Redinger RN

doi

10.1016/s0002-9610(02)01212-6

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

168-72

issue

eissn

0002-9610

issn

1879-1883

pii

S0002961002012126

journal_volume

185

pub_type

杂志文章,评审

在线工具

The coming of age of our understanding of the enterohepatic circulation of bile salts.