PPAR Research / 2009 / Article / Fig 2

Review Article

Regulation of Bile Acid and Cholesterol Metabolism by PPARs

Figure 2

Enterohepatic circulation of bile. Bile acids are transported across the canalicular membrane of hepatocytes by BSEP. Cholesterol is either converted into bile acids for biliary secretion or transported by ABCG5/G8 into the bile. MDR3 mediates biliary phospolipids secretion. Cholesterol, bile acids and phospholipids form mixed micelles to solublize cholesterol and reduce bile acid cytotoxicity. After food intake, gallbladder contracts and releases bile acids into intestine. Approximately 95% of bile acids are reabsorbed into the enterocytes. OST /OST heterodimeric transporter mediates basolateral bile acid efflux into the portal circulation. NTCP and OATPs mediate hepatic basolateral uptake of bile acids, which are then resecreted into the bile. In the hepatocytes, bile acid-activated FXR feedback inhibits CYP7A1 and NTCP, and thus bile acid synthesis and uptake. Bile acid-activated feed-forward stimulates BSEP and biliary bile acid secretion. Cholesterol derivatives oxysterols activate LXR, which induces ABCG5/G8 and biliary cholesterol secretion. In the intestine, FXR inhibits ASBT and stimulates IBABP and OST and OST .
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