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Regulation of gene expression by dietary plant sterols in cholesterol absorption and metabolism
Dietary plant sterol supplementation has long been used as an effective means to reduce cholesterol absorption efficiency and thus lower plasma low density lipoprotein (LDL) cholesterol concentrations. However, the exact mechanism by which plant sterols reduce cholesterol absorption has not been identified. Several mechanistic possibilities have been proposed and include plant sterol disruption of cholesterol solubility in intestinal micelles, plant sterol-cholesterol cocrystallization, and plant sterol competition with digestive enzymes. With the recent discovery of the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), it seems logical that plant sterols could also reduce cholesterol absorption through regulation of the NPC1L1 pathway. We hypothesized that the beneficial effects of plant sterols are, at least in part, due to the altered gene expression of NPC1L1. Male C57BL/6 mice were fed the AIN-93 diet (control), or the AIN-93 diet containing sitosterol or stigmasterol (2 g/2000 kcal) for 4 weeks. While plant sterol supplementation dramatically increased fecal neutral sterol excretion, intestinal expression of genes involved in cholesterol absorption and metabolism were unchanged. Livers of all mice accumulated plant sterols primarily in the form of sitosterol, while plant sterol supplemented mice accumulated significantly more sitosterol and stigmasterol compared to control mice. In addition to the accumulation of plant sterols, livers of mice that consumed diets containing plant sterol exhibited reduced expression of the transcription factor sterol response element binding protein 2 (SREBP-2) and its target gene HMG CoA reductase. In support of these data, we examined the mRNA expression of genes involved in cholesterol absorption and metabolism from the intestine-derived cell lines FHs 74 Int and CaCo-2 following treatment with plant sterols. In both cell lines there was a parallel reduction in mRNA expression of NPC1L1 and the SREBP-2 target gene HMG CoA reductase when treated with plant sterol. Our findings indicate that plant sterols alter the expression of genes involved in cholesterol transport, thus suggesting an intracellular mechanism—in addition to decreased micellar cholesterol solubility—by which plant sterols inhibit intestinal cholesterol absorption.^
Health Sciences, Nutrition
Jesch, Elliot D, "Regulation of gene expression by dietary plant sterols in cholesterol absorption and metabolism" (2008). ETD collection for University of Nebraska - Lincoln. AAI3330677.