Document Detail

Polyunsaturated fatty acids down-regulate in vitro expression of the key intestinal cholesterol absorption protein NPC1L1: no effect of monounsaturated nor saturated fatty acids.
MedLine Citation:
PMID:  19443194     Owner:  NLM     Status:  MEDLINE    
Several transporter proteins regulate intestinal cholesterol absorption. Of these proteins, NPC1L1 is a major contributor to this process. Fatty acids (FAs) modulate cholesterol absorption by a mechanism that remains unknown. We evaluate the effect of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) on the expression of NPC1L1 and others proteins associated with cholesterol absorption (SR-BI, ABCG5, ABCG8, ABCA1, CAV-1, ANX-2) in human enterocytes in vitro. The role of SREBPs, PPARs, LXR and RXR in this process was also investigated. Caco-2/TC-7 enterocytes were incubated for 24 h with a wide range of concentrations of FA-bovine serum albumin (50-300 microM). Gene expression was analyzed by quantitative real-time PCR. The NPC1L1 protein present in enterocyte membranes was analyzed using Western blot. NPC1L1 mRNA levels were reduced 35-58% by the n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (P<.05). Linoleic acid (n-6), palmitic acid and oleic acid did not affect NPC1L1 mRNA expression. ABCA1 mRNA levels were reduced 44-70% by n-6 arachidonic acid and 43-55% by n-3 EPA (P<.05). LXR and LXR+RXR agonists decreased NPC1L1 mRNA expression by 28% and 57%, respectively (P<.05). A concentration of 200 microM of EPA and DHA decreased NPC1L1 protein expression in enterocyte membranes by 58% and 59%, respectively. We have demonstrated that the PUFAs n-3 EPA and DHA down-regulate NPC1L1 mRNA expression. In addition, PUFAs also down-regulate NPC1L1 protein expression in enterocyte membranes. LXR and RXR activation induced a similar repression effect. The lipid-lowering effect of n-3 PUFAs could be mediated in part by their action at the NPC1L1 gene level.
Adriana Alvaro; Roser Rosales; Lluís Masana; Joan-Carles Vallvé
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-14
Journal Detail:
Title:  The Journal of nutritional biochemistry     Volume:  21     ISSN:  1873-4847     ISO Abbreviation:  J. Nutr. Biochem.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-17     Completed Date:  2010-10-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010081     Medline TA:  J Nutr Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  518-25     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, University Rovira and Virgili, Reus, CIBER de Diabetes y Enfermedades Metabólicas Asociadas, IISPV, Spain.
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MeSH Terms
Caco-2 Cells
Cholesterol / metabolism*
Docosahexaenoic Acids / metabolism
Eicosapentaenoic Acid / metabolism
Enterocytes / metabolism
Fatty Acids, Monounsaturated / metabolism
Fatty Acids, Unsaturated / metabolism*
Gene Expression Regulation*
Intestines / metabolism
Linoleic Acid / chemistry
Membrane Proteins / metabolism*
Models, Biological
Oleic Acid / chemistry
Palmitic Acid / metabolism
Reg. No./Substance:
0/Fatty Acids, Monounsaturated; 0/Fatty Acids, Unsaturated; 0/Membrane Proteins; 0/NPC1L1 protein, human; 112-80-1/Oleic Acid; 1553-41-9/Eicosapentaenoic Acid; 2197-37-7/Linoleic Acid; 25167-62-8/Docosahexaenoic Acids; 57-10-3/Palmitic Acid; 57-88-5/Cholesterol

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