Acute intake of plant stanol esters induces changes in lipid and lipoprotein metabolism-related gene expression in the liver and intestines of mice.
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.
Department of Human Biology, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Centre, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.
Els
E
De Smet
Ronald P
RP
Mensink
Maurice
M
Konings
Gemma
G
Brufau
Albert K
AK
Groen
Rick
R
Havinga
Marleen
M
Schonewille
Anja
A
Kerksiek
Dieter
D
Lütjohann
Jogchum
J
Plat
D000818:Animals; D000831:Animals, Newborn; D002784:Cholesterol / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007413:Intestinal Mucosa / Q000378:metabolism*; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors; D008297:Male; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D012855:Sitosterols / Q000097:blood / Q000493:pharmacokinetics*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism
D008074:Lipoproteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D011973:Receptors, LDL; D012855:Sitosterols; C497391:Srebf2 protein, mouse; D051782:Sterol Regulatory Element Binding Protein 2; C407042:plant stanol ester; D002784:Cholesterol; C472126:Pcsk9 protein, mouse; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases