Mardones P, Quiñones V, Amigo L, Moreno M, Miquel J F, Schwarz M, Miettinen H E, Trigatti B, Krieger M, VanPatten S, Cohen D E, Rigotti A
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile.
J Lipid Res. 2001 Feb;42(2):170-80.
The scavenger receptor class B type I (SR-BI), which is expressed in the liver and intestine, plays a critical role in cholesterol metabolism in rodents. While hepatic SR-BI expression controls high density lipoprotein (HDL) cholesterol metabolism, intestinal SR-BI has been proposed to facilitate cholesterol absorption. To evaluate further the relevance of SR-BI in the enterohepatic circulation of cholesterol and bile salts, we studied biliary lipid 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 cholesterol secretion, without concomitant changes in either biliary bile acid or phospholipid secretion. Hepatic total and unesterified cholesterol contents were slightly increased in SR-BI-deficient mice, while sterol synthesis was not significantly changed. Bile acid pool size and composition, as well as fecal bile acid excretion, were not altered in SR-BI knockout mice. Intestinal 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 selectively controlling the utilization of HDL cholesterol for biliary secretion. In contrast, SR-BI expression is not essential for intestinal cholesterol absorption.
I型B类清道夫受体（SR-BI）在肝脏和肠道中表达，在啮齿动物的胆固醇代谢中起关键作用。肝脏中的SR-BI表达控制高密度脂蛋白（HDL）胆固醇代谢，而肠道中的SR-BI则被认为有助于胆固醇吸收。为了进一步评估SR-BI在胆固醇和胆汁盐肝肠循环中的相关性，我们研究了SR-BI基因敲除小鼠的胆汁脂质分泌、肝脏固醇含量和合成、胆汁酸代谢、粪便中性固醇排泄以及肠道胆固醇吸收。SR-BI缺乏选择性地损害了胆汁胆固醇分泌，而胆汁酸或磷脂分泌没有相应变化。SR-BI基因敲除小鼠的肝脏总胆固醇和游离胆固醇含量略有增加，而固醇合成没有显著变化。SR-BI基因敲除小鼠的胆汁酸池大小和组成以及粪便胆汁酸排泄没有改变。相对于对照组，SR-BI基因敲除小鼠的肠道胆固醇吸收有所增加，粪便固醇排泄略有减少。这些发现证实了肝脏SR-BI表达在选择性控制HDL胆固醇用于胆汁分泌的利用方面的关键作用。相比之下，SR-BI表达对于肠道胆固醇吸收并非必不可少。
