Wang David Q-H, Lee Sum P
Department of Medicine, Liver Center and Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard Digestive Diseases Center, Boston, MA, USA.
Hepatology. 2008 Jul;48(1):177-85. doi: 10.1002/hep.22286.
Although many putative sterol transporters influencing cholesterol absorption and physical-chemical factors affecting dietary cholesterol absorption have been extensively investigated, it is still unclear how biliary cholesterol contributes to the regulation of intestinal cholesterol absorption. We studied whether the gallbladder can modulate the microaggregates of cholesterol carriers, which may in turn influence the intestinal absorption of biliary cholesterol. Supersaturated, crystallized, or micellar model biles were delivered via a duodenal catheter to conscious, freely moving C57L mice daily for 2 days. Intestinal uptake and absorption of biliary cholesterol and its fecal excretion, as well as expression levels of intestinal sterol transporters, were analyzed. Cholesterol uptake and absorption by the enterocyte were dramatically reduced in mice treated with crystallized biles compared with supersaturated biles. This correlated with the higher cumulative radioactivity of cholesterol recovered in the feces at 24 hours. Such findings were absent with the added reference compound sitostanol. After removing cholesterol crystals from crystallized biles, micellar biles showed essentially identical effects on intestinal absorption but with lower fecal cholesterol excretion compared with the original samples containing crystals. Expression levels of the jejunal Abcg5 (ATP-binding cassette transporter G5) and Abcg8, but not Npc1l1 (Niemann-Pick C1 like 1), were significantly increased by supersaturated biles compared with crystallized biles.
Different physical forms of biliary cholesterol dramatically determine intestinal uptake and absorption of cholesterol. Solid plate-like cholesterol monohydrate crystals in bile are probably not absorbed and are totally excreted in feces from the body. The gallbladder may have a role in regulating cholesterol homeostasis by modulating the physical forms of biliary cholesterol.
尽管许多影响胆固醇吸收的假定甾醇转运蛋白以及影响膳食胆固醇吸收的物理化学因素已得到广泛研究，但胆汁胆固醇如何调节肠道胆固醇吸收仍不清楚。我们研究了胆囊是否能调节胆固醇载体的微聚集体，而这反过来可能会影响胆汁胆固醇的肠道吸收。通过十二指肠导管每天向清醒、自由活动的C57L小鼠输送过饱和、结晶或胶束模型胆汁，持续2天。分析了胆汁胆固醇的肠道摄取、吸收及其粪便排泄，以及肠道甾醇转运蛋白的表达水平。与过饱和胆汁处理的小鼠相比，结晶胆汁处理的小鼠肠上皮细胞对胆固醇的摄取和吸收显著降低。这与24小时粪便中回收的胆固醇较高的累积放射性相关。添加参考化合物植物甾烷醇后未出现此类结果。从结晶胆汁中去除胆固醇晶体后，胶束胆汁对肠道吸收的影响基本相同，但与含有晶体的原始样品相比，粪便胆固醇排泄较低。与结晶胆汁相比，过饱和胆汁显著增加了空肠Abcg5（ATP结合盒转运蛋白G5）和Abcg8的表达水平，但未增加Npc1l1（尼曼-皮克C1样1）的表达水平。
胆汁胆固醇的不同物理形式显著决定了肠道对胆固醇的摄取和吸收。胆汁中的固体板状胆固醇一水合物晶体可能不被吸收，并从体内完全排泄到粪便中。胆囊可能通过调节胆汁胆固醇的物理形式在调节胆固醇稳态中发挥作用。
