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

Briand, O., Touche, V., Colin, S., Brufau, G., Davalos, A., Schonewille, M., Bovenga, F., Carriere, V., de Boer, J. F., Dugardin, C., Riveau, B., Clavey, V., Tailleux, A., Moschetta, A., Lasuncion, M. A., Groen, A. K., Staels, B. & Lestavel, S., Mar-2016, In : Gastroenterology. 150, 3, p. 650-658 9 p.

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  • Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Down

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DOI

  • Olivier Briand
  • Veronique Touche
  • Sophie Colin
  • Gemma Brufau
  • Alberto Davalos
  • Marleen Schonewille
  • Fabiola Bovenga
  • Veronique Carriere
  • Jan Freark de Boer
  • Camille Dugardin
  • Beatrice Riveau
  • Veronique Clavey
  • Anne Tailleux
  • Antonio Moschetta
  • Miguel A. Lasuncion
  • Albert K. Groen
  • Bart Staels
  • Sophie Lestavel

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
Publication statusPublished - Mar-2016

    Keywords

  • 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

ID: 37734951