胆固醇的胶束增溶作用对人体吸收至关重要。
Micellar solubilisation of cholesterol is essential for absorption in humans.
作者信息
Woollett L A, Wang Y, Buckley D D, Yao L, Chin S, Granholm N, Jones P J H, Setchell K D R, Tso P, Heubi J E
机构信息
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, and Department of Pediatrics, Clinical Research Center, Children's Hospital Medical Center, OH 45229, USA.
出版信息
Gut. 2006 Feb;55(2):197-204. doi: 10.1136/gut.2005.069906.
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 3beta hydroxy-C27 steroid dehydrogenase isomerase deficiency (3-HSD), two with Delta(4)-3-oxosteroid 5beta reductase deficiency (5beta 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 approximately 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.
背景与目的
肠腔内胆汁酸（BA）浓度对胆固醇吸收有深远影响。我们开展了多项研究，以评估BA合成先天性缺陷患儿肠腔内BA显著减少对胆固醇吸收的影响，以及在使用人肠内容物的动物模型中，胆固醇的胶束增溶作用对其吸收的影响。
方法
我们研究了5名受试者：2名患有3β-羟基-C27类固醇脱氢酶异构酶缺乏症（3-HSD），2名患有Δ4-3-氧代类固醇5β-还原酶缺乏症（5β-还原酶），1名患有2-甲基酰基辅酶A消旋酶缺乏症（消旋酶）。对受试者进行补充BA治疗，并在停用补充剂3周后进行研究。在每个治疗期间，受试者食用流质餐。收集并分析十二指肠样本，测量胆固醇吸收和胆固醇分数合成率。将人肠腔内内容物注入胆汁引流大鼠淋巴瘘模型，以评估胆固醇的胶束吸收与囊泡吸收情况。
结果
不补充BA时，肠腔内BA浓度低于临界胶束浓度（CMC），而补充BA的所有受试者肠腔内BA浓度均升高至高于CMC。未经治疗的受试者中，肠腔胆固醇主要以囊泡形式存在，而接受治疗的受试者中，胆固醇以胶束和囊泡两种形式存在。与未治疗的受试者相比，接受治疗的受试者胆固醇吸收增加了约55%（p = 0.041），同时合成率下降了70%（p = 0.029）。在大鼠淋巴瘘模型中，囊泡胆固醇吸收极少，而囊泡和胶束脂肪酸及磷脂的吸收相当。
结论
在BA合成先天性缺陷的受试者中，通过补充BA增加胶束胆固醇增溶作用，可改善胆固醇吸收，并因胆固醇胶束增溶作用的改善而降低胆固醇合成。
Zotero 插件