Abstract
The kinetics of plant stanol uptake and routing in 8-week-old C57BL/6J mice were determined after a plant stanol ester gavage. In addition, acute changes in intestinal and hepatic gene expression were investigated. Mice were fed a plant sterol/stanol poor diet from weaning. At the age of 8 weeks, they received an oral gavage consisting of 0.25 mg cholesterol + 50 mg plant stanol esters dissolved in olive oil. Animals were euthanized at different time points. In a second comparable set-up, mesenteric lymph-cannulated versus sham-operated mice received the same oral gavage, which was now deuterium labeled. Intestinal and hepatic sitostanol concentrations increased within 15 min post-gavage. This rapid hepatic appearance was absent in lymph-cannulated mice, suggesting a very fast lymph-mediated uptake. Hepatic mRNA expression of SREBP2 and its target genes rapidly decreased, whereas expression of LXR target genes increased. The intestinal SREBP2 pathway was increased, whereas the expression of LXR target genes hardly changed. The fivefold and sixfold increased expression of intestinal LDLr and PCSK9 is suggestive of TICE activation. We conclude that in C57BL/6J mice plant stanol kinetics are fast, and affect intestinal and hepatic gene expression within 15 min postprandial after lymph-mediated uptake.Electronic supplementary materialThe online version of this article (doi:10.1007/s11745-015-4020-1) contains supplementary material, which is available to authorized users.
Highlights
In humans, plant sterols and stanols lower intestinal cholesterol absorption, thereby reducing serum low-density lipoprotein cholesterol (LDL-C) concentrations up to 10 % at daily intakes of 2–2.5 g [1]
Intestinal expression of liver X receptor (LXR) target genes such as Niemann-Pick C1-Like protein 1 (NPC1L1), ABCA1, ABCG5, ABCG8 was not influenced after plant sterol or stanol intake [6]
We show that an acute bolus of dietary deuterium labeled sitostanol provided as sitostanol oleate appeared already after 15 min in the liver. This rapid hepatic appearance was absent in lymph-cannulated mice, suggesting a very fast lymph-mediated uptake, possible via pre-formed available chylomicrons
Summary
Plant sterols and stanols lower intestinal cholesterol absorption, thereby reducing serum low-density lipoprotein cholesterol (LDL-C) concentrations up to 10 % at daily intakes of 2–2.5 g [1]. Overexpression of the human gene encoding ATP-binding cassette transporter G5 and G8 (ABCG5, ABCG8) in the liver and the small intestine of C57BL/6J × SJL F2 mice reduced intestinal cholesterol absorption and promoted biliary cholesterol secretion [4]. These cholesterol transporter genes are under control of the liver X receptor (LXR), plant sterol and stanol ester feeding increased fecal neutral sterol excretion without changing intestinal LXR expression [5]. Intestinal expression of LXR target genes such as Niemann-Pick C1-Like protein 1 (NPC1L1), ABCA1, ABCG5, ABCG8 was not influenced after plant sterol or stanol intake [6]
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