Regulation of intestinal NPC1L1 expression by dietary fish oil and docosahexaenoic acid.
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 delta (PPARdelta) activation decreased NPC1L1 mRNA levels and cholesterol trafficking to the endoplasmic reticulum, suggesting that 22:6 may act through PPARdelta. 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 PPARdelta. Moreover, a diet enriched in n-3 fatty acids decreases the gene expression of NPC1L1 in duodenum and jejunum of hamster.
Mathur
Satya N
SN
Department of Veterans Affairs and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Watt
Kim R
KR
Field
F Jeffrey
FJ
D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D017306:Annexin A2 / Q000378:metabolism; D018938:Caco-2 Cells; D051242:Caveolin 1 / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005395:Fish Oils / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D009542:Niemann-Pick Diseases / Q000378:metabolism; D047494:PPAR delta / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D000097587:Sterol O-Acyltransferase 2
D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D017306:Annexin A2; D051242:Caveolin 1; D002784:Cholesterol; D004042:Dietary Fats, Unsaturated; D004281:Docosahexaenoic Acids; D005395:Fish Oils; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D047494:PPAR delta; D002785:Sterol O-Acyltransferase; D000097587:Sterol O-Acyltransferase 2; C416946:ABCG8 protein, human; C410800:NPC1L1 protein, human