Issn Print: 0954-691X
Publication Date: 2006/01/01
Intestinal expression of cholesterol transporter genes and chylomicron formation are not affected by dietary phytosterols and stanols in rodents
JK Kruit; Y Lin; T Plösch; R Havinga; WJ Kloots; VW Bloks; R Boverhof; GSMJE Duchateau; AK Groen; F Kuipers
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Excerpt
Phytosterols and stanols have successfully been introduced in functional foods to lower plasma LDL levels by reducing cholesterol absorption. The precise mechanism by which phytosterols and stanols exert this action is still unknown. In this study we addressed the hypothesis that phytosterols en stanols effect intestinal gene expression of cholesterol transporter genes and thereby affect chylomicron formation. Wistar and Wistar Kyoto (WKY) rats, which hyperabsorb phytosterols and stanols due to an Abcg5 mutation, were fed with either semi-synthetic control diet, cholesterol diet (0.11% w/w), cholesterol diet (0.11% w/w) with phytosterols (0.46% w/w) or cholesterol diet (0.11% w/w) with phytostanols (0.48% w/w) for 1 month (six animals/group). The effects of the diets on fecal sterol loss and on expression levels of genes involved in cholesterol homeostasis in the intestine were measured. Additionally, the effects of the diets on chylomicron secretion into lymph were examined in Wistar rats only. Addition of phytosterols or stanols to the cholesterol-enriched diet resulted in a dramatic increase in fecal cholesterol loss (+100–220%) in both strains of rats. However, this occurred without any significant change in intestinal expression of cholesterol transporter genes, like Npc1l1, Abca1, Abcg5 or Sr-b1 and of genes involved in esterification or synthesis of cholesterol in Wistar and WKY rats. The cholesterol-enriched diet increased cholesterol secretion into lymph 2.9-fold compared to control diet. This increase was fully prevented by addition of phytosterols or stanols to the diet. However, during intestinal infusion of 4% Intralipid®, cholesterol secretion into lymph and chylomicron composition were similar in all groups.
Conclusions Phytosterols and stanols strongly reduced cholesterol absorption efficiency without altering intestinal gene expression profiles in Wistar rats and in the phytosterol/stanol hyperabsorbing WKY rats. No sustained effects on chylomicron secretion were observed when phytosterols/stanols were added to the diet. Our data strongly indicate that phytosterols and stanols act at the level of the intestinal lumen, probably by mechanisms such as interference with mixed micelle formation.
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