Plat Jogchum, Mensink Ronald P
Department of Human Biology, Maastricht University, Maastricht, Netherlands.
FASEB J. 2002 Aug;16(10):1248-53. doi: 10.1096/fj.01-0718hyp.
The hypocholesterolemic effect of plant stanols is explained by a decreased intestinal cholesterol absorption due to a competition between plant stanols and cholesterol for incorporation into mixed micelles. Earlier we had suggested that plant stanols have a so far unknown action inside the enterocytes. The recent discovery of the involvement of ATP binding cassette (ABC) transporters in cholesterol absorption was a lead to further explore the hypocholesterolemic mechanism of plant stanols. We found that mixed micelles enriched with sitostanol or with cholesterol plus sitostanol were potent inducers of ABCA1 expression in caco-2 cells, an accepted model to study human intestinal lipoprotein metabolism. Based on these findings, we now hypothesize that plant stanols--and possibly plant sterols--increase ABCA1-mediated cholesterol efflux back into the intestinal lumen. We further hypothesize that intracellular levels of plant stanols are monitored by the same sensors (SREBP-2 and LXR) as those that monitor cholesterol. Consequently, increased plant stanol levels within the enterocyte activate cholesterol efflux through ABCA1- but not SREBP-2-mediated endogenous cholesterol synthesis even if intracellular cholesterol concentrations are lowered through consumption of plant stanols. If our hypothesis is correct, then the LXR pathway may be a target for dietary regulation of intestinal lipid metabolism.
植物甾烷醇的降胆固醇作用是由于植物甾烷醇与胆固醇竞争掺入混合微团，导致肠道胆固醇吸收减少所致。此前我们曾提出植物甾烷醇在肠细胞内有迄今未知的作用。最近发现ATP结合盒（ABC）转运蛋白参与胆固醇吸收，这为进一步探索植物甾烷醇的降胆固醇机制提供了线索。我们发现，富含谷甾烷醇或胆固醇加谷甾烷醇的混合微团是Caco-2细胞中ABCA1表达的有效诱导剂，Caco-2细胞是研究人类肠道脂蛋白代谢的公认模型。基于这些发现，我们现在推测植物甾烷醇以及可能的植物甾醇会增加ABCA1介导的胆固醇向肠腔的流出。我们进一步推测，植物甾烷醇的细胞内水平由与监测胆固醇相同的传感器（SREBP-2和LXR）监测。因此，即使通过食用植物甾烷醇降低了细胞内胆固醇浓度，肠细胞内植物甾烷醇水平的升高也会通过ABCA1而非SREBP-2介导的内源性胆固醇合成激活胆固醇流出。如果我们的假设正确，那么LXR途径可能是肠道脂质代谢饮食调节的靶点。
