Physical chemistry of intestinal absorption of biliary cholesterol in mice
Physical chemistry of intestinal absorption of biliary cholesterol in mice
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DOI：
10.1002/hep.22286
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发表时间：
2008-07
期刊：
影响因子：
13.5
通讯作者：
D. Q. Wang;S. Lee
中科院分区：
文献类型：
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作者：
D. Q. Wang;S. Lee
虽然许多公认的影响胆固醇吸收的固醇转运蛋白和影响膳食胆固醇吸收的理化因素已被广泛研究，但胆汁胆固醇如何参与肠道胆固醇吸收的调节仍不清楚。我们研究了胆囊是否可以调节胆固醇载体的微聚集体，这可能反过来影响胆汁胆固醇的肠道吸收。通过十二指肠导管将过饱和、结晶或胶束模型胆汁递送至清醒、自由活动的C57 L小鼠，每天持续2天。分析胆汁胆固醇的肠道摄取和吸收及其粪便排泄，以及肠道固醇转运蛋白的表达水平。与过饱和胆汁相比，用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减少。这与24小时时粪便中回收的胆固醇累积放射性较高相关。加入参比化合物谷甾烷醇后，不存在此类结果。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，粪便胆固醇排泄量较低。与结晶胆汁相比，过饱和胆汁显著增加了空肠Abcg 5（ATP结合盒转运体G5）和Abcg 8的表达水平，但Npc 1 l1（Niemann-Pick C1样1）没有显著增加。结论：胆汁胆固醇的不同物理形态显著地决定了胆固醇的肠道摄取和吸收。胆汁中的固体板状胆固醇一水合物晶体可能不会被吸收，并完全通过粪便从体内排出。胆囊可能通过调节胆汁胆固醇的物理形式来调节胆固醇稳态。（肝脏学2008年）
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. Conclusion: 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. (HEPATOLOGY 2008.)