Hepatic cholesterol and bile acid metabolism and intestinal cholesterol absorption in scavenger receptor class B type I-deficient mice

The scavenger receptor class B type I (SR-BI), which is expressed in the li ver and intestine, plays a critical role in cholesterol metabolism in roden ts. While hepatic SR-BI expression controls high density lipoprotein (HDL) cholesterol metabolism, intestinal SR-BI has been proposed to facilitate ch olesterol absorption. To evaluate further the relevance of SR-BI in the ent erohepatic circulation of cholesterol and bile salts, we studied biliary li pid secretion, hepatic sterol content and synthesis, bile acid metabolism, fecal neutral sterol excretion, and intestinal cholesterol absorption in SR -BI knockout mice. SR-BI deficiency selectively impaired biliary cholestero l secretion, without concomitant changes in either biliary bile acid or pho spholipid secretion. Hepatic total and unesterified cholesterol contents we re slightly increased in SR-BI-deficient mice, while sterol synthesis was n ot significantly changed, Bile acid pool size and composition, as well as f ecal bile acid excretion, were not altered in SR-BI knockout mice. Intestin al cholesterol absorption was somewhat increased and fecal sterol excretion was slightly decreased in SR-BI knockout mice relative to controls. These findings establish the critical role of hepatic SR-BI expression in selecti vely controlling the utilization of HDL cholesterol for biliary secretion. In contrast, SR-BI expression is not essential for intestinal cholesterol a bsorption.