A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine

H.M. van den Bosch, N.J.W. de Wit, G.J.E.J. Hooiveld, H. Vermeulen, J.N. van der Veen, S.M. Houten, F. Kuipers, M.R. Müller, R. van der Meer

Research output: Contribution to journalArticleAcademicpeer-review

51 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)G1171-G1180
JournalAmerican Journal of Physiology. Gastrointestinal and Liver Physiology
Issue number5
Publication statusPublished - 2008


  • liver-x-receptor
  • cellular cholesterol
  • caco-2 cells
  • lxr-alpha
  • absorption
  • mice
  • secretion
  • metabolism
  • activation
  • excretion


Dive into the research topics of 'A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine'. Together they form a unique fingerprint.

Cite this