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

Olivier Briand1, Véronique Touche1, Sophie Colin1

  • 1University Lille, Inserm, Centre Hospitalier Universitaire (CHU) de Lille, Institut Pasteur de Lille, U1011-European Genomic Institute for Diabetes, Lille, France.

Gastroenterology
|November 26, 2015
PubMed
Abstract

Insights

Activating intestinal liver X receptors (LXRs) reduces chylomicron production by altering scavenger receptor class B, type 1 (SR-B1) localization. This finding offers a potential strategy for managing postprandial triglyceridemia in obesity and type 2 diabetes.

Area of Science:

  • Metabolic research
  • Molecular biology
  • Gastroenterology

Background:

  • Postprandial triglyceridemia is linked to cardiovascular risks in obesity and type 2 diabetes.
  • Enterocyte scavenger receptor class B, type 1 (SR-B1) is crucial for chylomicron assembly and secretion.
  • Liver X receptors (LXRs) regulate lipid metabolism, but their role in intestinal triglyceride absorption is unclear.

Purpose of the Study:

  • To investigate whether intestinal LXRs regulate triglyceride absorption.
  • To elucidate the mechanism by which LXRs influence chylomicron production.

Main Methods:

  • Mice were fed cholesterol-enriched diets or treated with LXR agonists (GW3965, T0901317).
  • Chylomicron production and SR-B1 localization were assessed in mice and Caco-2/TC7 cells.
  • Mechanisms of SR-B1 regulation by LXRs were studied in vitro.

Main Results:

  • LXR agonists induced SR-B1 internalization from apical membranes in enterocytes.
  • Chylomicron secretion and lipid-micelle-induced Erk phosphorylation were reduced by LXR activation.
  • LXR activation reduced SR-B1 levels via a post-transcriptional mechanism involving microRNAs.

Conclusions:

  • Intestinal LXR activation reduces chylomicron production.
  • This effect is dependent on the regulation of SR-B1 apical localization.
  • Targeting intestinal LXRs may offer a novel therapeutic approach for metabolic disorders.
Keywords:
Fat AbsorptionHypertriglyceridemiaLipid-SensingTriglyceride-Rich Lipoproteins

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