Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Down-regulation of Scavenger Receptor Class B, Type 1

被引：40

作者：

Briand, Olivier ^{[1
]}

Touche, Veronique ^{[1
]}

Colin, Sophie ^{[1
]}

Brufau, Gemma ^{[2
]}

Davalos, Alberto ^{[3
]}

Schonewille, Marleen ^{[2
]}

Bovenga, Fabiola ^{[4
,5
]}

Carriere, Veronique ^{[7
,8
,9
]}

de Boer, Jan Freark ^{[2
]}

Dugardin, Camille ^{[1
]}

Riveau, Beatrice ^{[6
,7
,8
]}

Clavey, Veronique ^{[1
]}

Tailleux, Anne ^{[1
]}

Moschetta, Antonio ^{[4
,5
]}

Lasuncion, Miguel A. ^{[9
,10
]}

Groen, Albert K. ^{[2
]}

Staels, Bart ^{[1
]}

Lestavel, Sophie ^{[1
]}

机构：

[1] Univ Lille, INSERM, Ctr Hosp Univ CHU Lille, Inst Pasteur Lille,U1011,European Genom Inst Diab, Lille, France

[2] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat, NL-9700 AB Groningen, Netherlands

[3] UAM, Madrid Inst Adv Studies IMDEA Food Inst, Lab Disorders Lipid Metab & Mol Nutr, CSIC, CEI, Madrid, Spain

[4] Natl Res Canc Ctr, Giovanni Paolo 2, Bari, Italy

[5] Univ Bari, Bari, Italy

[6] Univ Paris 06, Sorbonne Univ, UMR S 1138, Ctr Rech Cordeliers, Paris, France

[7] Ctr Rech Cordeliers, INSERM, UMR S 1138, Paris, France

[8] Univ Paris 05, Sorbonne Paris Cit, UMR S 1138, Ctr Rech Cordeliers, Paris, France

[9] Hosp Ramon & Cajal, IRYCIS, Serv Bioquim Invest, E-28034 Madrid, Spain

[10] Inst Salud Carlos III, Ctr Invest Biomed Red CIBER Fisiopatol Obesidad &, Madrid, Spain

来源：

GASTROENTEROLOGY | 2016年 / 150卷 / 03期

关键词：

Hypertriglyceridemia; Lipid-Sensing; Fat Absorption; Triglyceride-Rich Lipoproteins; DENSITY-LIPOPROTEIN METABOLISM; POSTPRANDIAL LIPID-METABOLISM; REVERSE CHOLESTEROL TRANSPORT; SR-BI; HDL-CHOLESTEROL; LXR-ALPHA; EXPRESSION; ENTEROCYTES; MICE; GENE;

D O I：

10.1053/j.gastro.2015.11.015

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BACKGROUND & AIMS: Reducing postprandial triglyceridemia may be a promising strategy to lower the risk of cardiovascular disorders associated with obesity and type 2 diabetes. In enterocytes, scavenger receptor class B, type 1 (SR-B1, encoded by SCARB1) mediates lipid-micelle sensing to promote assembly and secretion of chylomicrons. The nuclear receptor subfamily 1, group H, members 2 and 3 (also known as liver X receptors [LXRs]) regulate genes involved in cholesterol and fatty acid metabolism. We aimed to determine whether intestinal LXRs regulate triglyceride absorption. METHODS: C57BL/6J mice were either fed a cholesterol-enriched diet or given synthetic LXR agonists (GW3965 or T0901317). We measured the production of chylomicrons and localized SR-B1 by immunohistochemistry. Mechanisms of postprandial triglyceridemia and SR-B1 regulation were studied in Caco-2/TC7 cells incubated with LXR agonists. RESULTS: In mice and in the Caco-2/TC7 cell line, LXR agonists caused localization of intestinal SR-B1 from apical membranes to intracellular organelles and reduced chylomicron secretion. In Caco-2/TC7 cells, LXR agonists reduced SR-B1-dependent lipidic-micelle-induced Erk phosphorylation. LXR agonists also reduced intracellular trafficking of the apical apolipoprotein B pool toward secretory compartments. LXR reduced levels of SR-B1 in Caco-2/TC7 cells via a post-transcriptional mechanism that involves microRNAs. CONCLUSION: In Caco-2/TC7 cells and mice, intestinal activation of LXR reduces the production of chylomicrons by a mechanism dependent on the apical localization of SR-B1.

引用

页码：650 / 658

页数：9

共 46 条

[1] Identification of scavenger receptor SR-BI as a high density lipoprotein receptor [J].

Acton, S ;

Rigotti, A ;

Landschulz, KT ;

Xu, SZ ;

Hobbs, HH ;

Krieger, M .

SCIENCE, 1996, 271 (5248) :518-520

[2] Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women [J].

Bansal, Sandeep ;

Buring, Julie E. ;

Rifai, Nader ;

Mora, Samia ;

Sacks, Frank M. ;

Ridker, Paul M. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2007, 298 (03) :309-316

[3] Sensing of Dietary Lipids by Enterocytes: A New Role for SR-BI/CLA-1 [J].

Beaslas, Olivier ;

Cueille, Carine ;

Delers, Francois ;

Chateau, Danielle ;

Chambaz, Jean ;

Rousset, Monique ;

Carriere, Veronique .

PLOS ONE, 2009, 4 (01)

[4] Accelerated lipid absorption in mice overexpressing intestinal SR-BI [J].

Bietrix, F ;

Yan, DG ;

Nauze, M ;

Rolland, C ;

Bertrand-Michel, J ;

Caméra, C ;

Schaak, S ;

Barbaras, R ;

Groen, AK ;

Perret, B ;

Tercé, F ;

Collet, X .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (11) :7214-7219

[5] Tissue-specific induction of intestinal ABCA1 expression with a liver x receptor agonist raises plasma HDL cholesterol levels [J].

Brunham, Liam R. ;

Kruit, Janine K. ;

Pape, Terry D. ;

Parks, John S. ;

Kuipers, Folkert ;

Hayden, Michael R. .

CIRCULATION RESEARCH, 2006, 99 (07) :672-674

[6]

Cai SF, 2001, J LIPID RES, V42, P902

[7]

CALVO D, 1993, J BIOL CHEM, V268, P18929

[8] Activation of intestinal peroxisome proliferator-activated receptor- increases high-density lipoprotein production [J].

Colin, Sophie ;

Briand, Olivier ;

Touche, Veronique ;

Wouters, Kristiaan ;

Baron, Morgane ;

Pattou, Francois ;

Hanf, Remy ;

Tailleux, Anne ;

Chinetti, Giulia ;

Staels, Bart ;

Lestavel, Sophie .

EUROPEAN HEART JOURNAL, 2013, 34 (32) :2566-+

[9] Comparison of class B scavenger receptors, CD36 and scavenger receptor BI (SR-BI), shows that both receptors mediate high density lipoprotein-cholesteryl ester selective uptake but SR-BI exhibits a unique enhancement of cholesteryl ester uptake [J].

Connelly, MA ;

Klein, SM ;

Azhar, S ;

Abumrad, NA ;

Williams, DL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (01) :41-47

[10] Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids [J].

Cruz-Garcia, Lourdes ;

Schlegel, Amnon .

JOURNAL OF LIPID RESEARCH, 2014, 55 (09) :1944-1958

← 1 2 3 4 5 →