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 journalArticle

13 Citations (Scopus)

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

Fingerprint

CD36 Antigens
Intestinal Absorption
Triglycerides
Down-Regulation
Caco-2 Cells
Chylomicrons
Micelles
Liver X Receptors
Cholesterol
Intracellular Membranes
Enterocytes
Apolipoproteins B
MicroRNAs
Inbred C57BL Mouse
Organelles
Type 2 Diabetes Mellitus
Fatty Acids

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Briand, O., Touche, V., Colin, S., Brufau, G., Davalos, A., Schonewille, M., ... Lestavel, S. (2016). Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Down-regulation of Scavenger Receptor Class B, Type 1. Gastroenterology, 150(3), 650-658. https://doi.org/10.1053/j.gastro.2015.11.015

Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Down-regulation of Scavenger Receptor Class B, Type 1. / Briand, Olivier; Touche, Véronique; Colin, Sophie; Brufau, Gemma; Davalos, Alberto; Schonewille, Marleen; Bovenga, Fabiola; Carrière, Véronique; De Boer, Jan Freark; Dugardin, Camille; Riveau, Béatrice; Clavey, Véronique; Tailleux, Anne; Moschetta, Antonio; Lasunción, Miguel A.; Groen, Albert K.; Staels, Bart; Lestavel, Sophie.

In: Gastroenterology, Vol. 150, No. 3, 01.03.2016, p. 650-658.

Research output: Contribution to journalArticle

Briand, O, Touche, V, Colin, S, Brufau, G, Davalos, A, Schonewille, M, Bovenga, F, Carrière, V, De Boer, JF, Dugardin, C, Riveau, B, Clavey, V, Tailleux, A, Moschetta, A, Lasunción, MA, Groen, AK, Staels, B & Lestavel, S 2016, 'Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Down-regulation of Scavenger Receptor Class B, Type 1', Gastroenterology, vol. 150, no. 3, pp. 650-658. https://doi.org/10.1053/j.gastro.2015.11.015
Briand, Olivier ; Touche, Véronique ; Colin, Sophie ; Brufau, Gemma ; Davalos, Alberto ; Schonewille, Marleen ; Bovenga, Fabiola ; Carrière, Véronique ; De Boer, Jan Freark ; Dugardin, Camille ; Riveau, Béatrice ; Clavey, Véronique ; Tailleux, Anne ; Moschetta, Antonio ; Lasunción, Miguel A. ; Groen, Albert K. ; Staels, Bart ; Lestavel, Sophie. / Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Down-regulation of Scavenger Receptor Class B, Type 1. In: Gastroenterology. 2016 ; Vol. 150, No. 3. pp. 650-658.
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T1 - Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Down-regulation of Scavenger Receptor Class B, Type 1

AU - Briand, Olivier

AU - Touche, Véronique

AU - Colin, Sophie

AU - Brufau, Gemma

AU - Davalos, Alberto

AU - Schonewille, Marleen

AU - Bovenga, Fabiola

AU - Carrière, Véronique

AU - De Boer, Jan Freark

AU - Dugardin, Camille

AU - Riveau, Béatrice

AU - Clavey, Véronique

AU - Tailleux, Anne

AU - Moschetta, Antonio

AU - Lasunción, Miguel A.

AU - Groen, Albert K.

AU - Staels, Bart

AU - Lestavel, Sophie

PY - 2016/3/1

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N2 - 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.

AB - 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.

KW - Fat Absorption

KW - Hypertriglyceridemia

KW - Lipid-Sensing

KW - Triglyceride-Rich Lipoproteins

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