Micellar solubilisation of cholesterol is essential for absorption in humans

被引:58
作者
Woollett, LA
Wang, Y
Buckley, DD
Yao, L
Chin, S
Granholm, N
Jones, PJH
Setchell, KDR
Tso, P
Heubi, JE
机构
[1] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Clin Res Ctr,Div Pediat & Pathol, Cincinnati, OH 45229 USA
[2] Univ Cincinnati, Coll Med, Dept Pathol & Lab Med, Cincinnati, OH USA
[3] CNR, Inst Nutrisci & Hlth, Charlottetown, PE, Canada
[4] McGill Univ, Sch Dietet & Human Nutr, Montreal, PQ, Canada
[5] Childrens Hosp Med Ctr, Div Pediat Gastroenterol Hepatol & Nutr, Cincinnati, OH USA
关键词
D O I
10.1136/gut.2005.069906
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and aims: Intralumenal bile acid ( BA) concentrations have a profound effect on cholesterol absorption. We performed studies to assess the effects of markedly reduced lumenal BA on cholesterol absorption in children with inborn errors in BA synthesis and the role of micellar solubilisation of cholesterol on its absorption in an animal model using human intestinal contents. Methods: We studied five subjects: two with 3 beta hydroxy-C-27 steroid dehydrogenase isomerase deficiency (3-HSD), two with Delta(4)-3-oxosteroid 5 beta reductase deficiency (5 beta reductase), and one with 2-methylacyl CoA racemase deficiency (racemase). Subjects were studied on supplemental BA therapy and three weeks after withdrawal of supplements. During each treatment period a liquid meal was consumed. Duodenal samples were collected and analysed, and cholesterol absorption and cholesterol fractional synthetic rates were measured. Human intralumenal contents were infused in a bile diverted rat lymph fistula model to assess micellar versus vesicular absorption of cholesterol. Results: Without BA supplementation, intralumenal BA concentrations were below the critical micellar concentration (CMC) whereas intralumenal BAs increased to above the CMC in all subjects on BA supplementation. Lumenal cholesterol was carried primarily as vesicles in untreated subjects whereas it was carried as both micelles and vesicles in treated subjects. Cholesterol absorption increased approximate to 55% in treated compared with untreated subjects (p = 0.041), with a simultaneous 70% decrease in synthesis rates (p = 0.029). In the rat lymph fistula model, minimal vesicular cholesterol was absorbed whereas vesicular and micellar fatty acid and phospholipid were comparably absorbed. Conclusions: Increasing micellar cholesterol solubilisation by supplemental BA in subjects with inborn errors of BA synthesis leads to an improvement in cholesterol absorption and reduction in cholesterol synthesis due to improved micellar solubilisation of cholesterol.
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页码:197 / 204
页数:8
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