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1 Human Nutrition, Wageningen University, Wageningen, Netherlands; Nutrigenomics Consortium, TI FOOD and Nutrition, Netherlands
2 Human Nutrition, Wageningen University, Wageningen, Netherlands; United States; Nutrigenomics Consortium, TI FOOD and Nutrition, Netherlands
3 Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Medical Center Groningen, Groningen, Netherlands
4 Department of Pediatrics/Emma Childrens's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
5 Nutrigenomics Consortium, TI FOOD and Nutrition, Netherlands; Laboratory of Pediatrics, University Medical Center Groningen, Center for Liver, Digestive and Metabolic Disease, Netherlands
6 Human Nutrition, Wageningen University, Wageningen, Netherlands; Nutrigenomics Consortium, TI Food and Nutrition, Wageningen, Netherlands; NIZO Food Research, Ede, Netherlands
* To whom correspondence should be addressed. E-mail: nicole.dewit{at}wur.nl.
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 towards plasma HDL and back into the intestinal lumen, respectively. Abca1, Abcg5, and Abcg8 are well-established 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 down-regulated after 2, 4, and 8 weeks 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 down-regulation occurs within a 6 hours time frame. Studies in LXR
-null mice, confirmed by in vitro data, showed that fatty acid-induced down-regulation of cholesterol transporters is LXR-independent and associated with a post-translational increase in Hmg-CoA 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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  D. V. Nguyen, V. A. Drover, M. Knopfel, P. Dhanasekaran, H. Hauser, and M. C. Phillips Influence of class B scavenger receptors on cholesterol flux across the brush border membrane and intestinal absorption J. Lipid Res., November 1, 2009; 50(11): 2235 - 2244. [Abstract] [Full Text] [PDF]
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