Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Down-regulation of Scavenger Receptor Class B, Type 1
Copyright policy )Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Down-regulation of Scavenger Receptor Class B, Type 1
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.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.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.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.
- University of Groningen Netherlands
- Autonomous University of Madrid Spain
- Inserm France
- University of Paris France
- Spanish National Research Council Spain
EXPRESSION, Male, Benzylamines, Fat absorption, Hydrocarbons, Fluorinated, POSTPRANDIAL LIPID-METABOLISM, Down-Regulation, Triglyceride-rich lipoproteins, Lipid-sensing, Benzoates, Cholesterol, Dietary, DEAD-box RNA Helicases, Fat Absorption, HDL-CHOLESTEROL, Chylomicrons, Animals, Humans, Triglyceride-Rich Lipoproteins, DENSITY-LIPOPROTEIN METABOLISM, Intestinal Mucosa, Apolipoproteins B, Liver X Receptors, Hypertriglyceridemia, Mice, Knockout, Lipid-Sensing, LXR-ALPHA, REVERSE CHOLESTEROL TRANSPORT, ENTEROCYTES, SR-BI, GENE, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, MICE, MicroRNAs, Jejunum, Intestinal Absorption, Apolipoprotein B-100, Caco-2 Cells
EXPRESSION, Male, Benzylamines, Fat absorption, Hydrocarbons, Fluorinated, POSTPRANDIAL LIPID-METABOLISM, Down-Regulation, Triglyceride-rich lipoproteins, Lipid-sensing, Benzoates, Cholesterol, Dietary, DEAD-box RNA Helicases, Fat Absorption, HDL-CHOLESTEROL, Chylomicrons, Animals, Humans, Triglyceride-Rich Lipoproteins, DENSITY-LIPOPROTEIN METABOLISM, Intestinal Mucosa, Apolipoproteins B, Liver X Receptors, Hypertriglyceridemia, Mice, Knockout, Lipid-Sensing, LXR-ALPHA, REVERSE CHOLESTEROL TRANSPORT, ENTEROCYTES, SR-BI, GENE, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, MICE, MicroRNAs, Jejunum, Intestinal Absorption, Apolipoprotein B-100, Caco-2 Cells
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