Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 372514
Title A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine
Author(s) Bosch, H.M. van den; Wit, N.J.W. de; Hooiveld, G.J.E.J.; Vermeulen, H.; Veen, J.N. van der; Houten, S.M.; Kuipers, F.; Müller, M.R.; Meer, R. van der
Source American Journal of Physiology. Gastrointestinal and Liver Physiology 294 (2008)5. - ISSN 0193-1857 - p. G1171 - G1180.
Department(s) VLAG
Chair Nutrition Metabolism and Genomics
Human Nutrition (HNE)
Publication type Refereed Article in a scientific journal
Publication year 2008
Keyword(s) liver-x-receptor - cellular cholesterol - caco-2 cells - lxr-alpha - absorption - mice - secretion - metabolism - activation - excretion
Abstract Transporters present in the epithelium of the small intestine determine the efficiency by which dietary and biliary cholesterol are taken up into the body and thus control whole-body cholesterol balance. Niemann-Pick C1 Like Protein 1 (Npc1l1) transports cholesterol into the enterocyte, whereas ATP-binding cassette transporters Abca1 and Abcg5/Abcg8 are presumed to be involved in cholesterol efflux from the enterocyte toward plasma HDL and back into the intestinal lumen, respectively. Abca1, Abcg5, and Abcg8 are well-established liver X receptor (LXR) target genes. We examined the effects of a high-fat diet on expression and function of cholesterol transporters in the small intestine in mice. Npc1l1, Abca1, Abcg5, and Abcg8 were all downregulated after 2, 4, and 8 wk on a cholesterol-free, high-fat diet. The high-fat diet did not affect biliary cholesterol secretion but diminished fractional cholesterol absorption from 61 to 42% (P <0.05). In an acute experiment in which triacylglycerols of unsaturated fatty acids were given by gavage, we found that this downregulation occurs within a 6-h time frame. Studies in LXR-null mice, confirmed by in vitro data, showed that fatty acid-induced downregulation of cholesterol transporters is LXR independent and associated with a posttranslational increase in 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity that reflects induction of cholesterol biosynthesis as well as with a doubling of neutral fecal sterol loss. This study highlights the induction of adaptive changes in small intestinal cholesterol metabolism during exposure to dietary fat.
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