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Journal of Lipid Research, Vol. 48, 395-404, February 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Regulation of intestinal NPC1L1 expression by dietary fish oil and docosahexaenoic acid

Satya N. Mathur, Kim R. Watt and F. Jeffrey Field¹

Department of Veterans Affairs and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242

Published, JLR Papers in Press, November 18, 2006.

¹ To whom correspondence should be addressed. e-mail: f-jeffrey-field{at}uiowa.edu

To address the effect of the n-3 fatty acid, docosahexaenoic acid (22:6), on proteins that play a role in cholesterol absorption, CaCo-2 cells were incubated with taurocholate micelles alone or micelles containing 22:6 or oleic acid (18:1). Compared with controls or 18:1, 22:6 did not interfere with the cellular uptake of micellar cholesterol. Apical cholesterol efflux was enhanced in cells incubated with 22:6. Cholesterol trafficking from the plasma membrane to the endoplasmic reticulum was decreased by 22:6. 22:6 decreased Niemann-Pick C1-Like 1 (NPC1L1) protein and mRNA levels without altering gene or protein expression of ACAT2, annexin-2, caveolin-1, or ABCG8. Peroxisome proliferator-activated receptor (PPAR) activation decreased NPC1L1 mRNA levels and cholesterol trafficking to the endoplasmic reticulum, suggesting that 22:6 may act through PPAR. Compared with hamsters fed a control diet or olive oil (enriched 18:1), NPC1L1 mRNA levels were decreased in duodenum and jejunum of hamsters ingesting fish oil (enriched 22:6). In an intestinal cell, independent of changes in ABCG8 expression, 22:6 increases the apical efflux of cholesterol. 22:6 interferes with cholesterol trafficking to the endoplasmic reticulum by the suppression of NPC1L1, perhaps through the activation of PPAR. Moreover, a diet enriched in n-3 fatty acids decreases the gene expression of NPC1L1 in duodenum and jejunum of hamster.

Supplementary key words intestine • Niemann-Pick C1-Like 1 • cholesterol • n-3 fatty acids • cholesterol trafficking

Abbreviations: BB, brush-border membrane; NBBM, non-brush-border membrane; NPC1L1, Niemann-Pick C1-Like 1; PPAR, peroxisome proliferator-activated receptor ; SREBP-1c, sterol-regulatory element binding protein 1c; 18:1, oleic acid; 20:5, eicosapentaenoic acid; 22:6, docosahexaenoic acid

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