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

Olivier Briand, Véronique Touche, Sophie Colin, Gemma Brufau, Alberto Davalos, Marleen Schonewille, Fabiola Bovenga, Véronique Carrière, Jan Freark De Boer, Camille Dugardin, Béatrice Riveau, Véronique Clavey, Anne Tailleux, Antonio Moschetta, Miguel A. Lasunción, Albert K. Groen, Bart Staels, Sophie Lestavel

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)650-658
Number of pages9
JournalGastroenterology
Volume150
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Keywords

  • Fat Absorption
  • Hypertriglyceridemia
  • Lipid-Sensing
  • Triglyceride-Rich Lipoproteins

ASJC Scopus subject areas

  • Gastroenterology

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