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; Dávalos, Alberto; Schonewille, Marleen; Bovenga, Fabiola; Carrière, Véronique; Boer, Jan Freark de; Dugardin, Camille; Riveau, Béatrice; Clavey, Véronique; Tailleux, Anne; Moschetta, Antonio; Lasunción, Miguel A.; Groen, Albert K.; Staels, Bart; Lestavel, Sophie

doi:10.1053/j.gastro.2015.11.015

Cited by 41 publications

(29 citation statements)

References 45 publications

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“…We found that morin indeed alleviated the lipid accumulation, improved morphology in hepatic tissues, lowered TG contents and ameliorated liver damage, which is in agreement with observations with other LXR antagonist and a liver‐specific reverse agonist (Huang, ). LXRs may directly modulate the hepatic lipogenesis or affect the absorption of TGs in the intestine (Briand et al , ). Since morin did not change the TG content of faeces (Figure E), we analysed the inhibitory effects of morin on lipogenesis in 3T3‐L1 adipocytes and hepatic HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

Morin, a novel liver X receptor α/β dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases

Zhang

Liu

et al. 2017

British J Pharmacology

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Section: Discussionmentioning

confidence: 99%

Morin, a novel liver X receptor α/β dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases

Zhang

Liu

et al. 2017

British J Pharmacology

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“…Genetic activation of Lxrα in the intestine blunts cholesterol absorption (Lo Sasso et al, 2010) and fatty acid absorption (Cruz-Garcia and Schlegel, 2014); and drives the absorbed lipids into a cytoplasmic lipid droplet pool (Cruz-Garcia and Schlegel, 2014). Pharmacological activation of intestinal Lxrs also blunts fatty acid absorption and transport (Briand et al, 2016). Conversely, global deletion of mouse Lxrα increases the fraction of dietary cholesterol that is absorbed in the presence of a non-sterol Lxr agonist, an effect not seen when Lxrβ is deleted (Hu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Role of Intestinal LXRα in Regulating Post-prandial Lipid Excursion and Diet-Induced Hypercholesterolemia and Hepatic Lipid Accumulation

2017

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Post-prandial hyperlipidemia has emerged as a cardiovascular risk factor with limited therapeutic options. The Liver X receptors (Lxrs) are nuclear hormone receptors that regulate cholesterol elimination. Knowledge of their role in regulating the absorption and handling of dietary fats is incomplete. The purpose of this study was to determine the role of intestinal Lxrα in post-prandial intestinal lipid transport. Using Lxrα knockout (nr1h3−/−) and intestine-limited Lxrα over-expressing [Tg(fabp2a:EGFP-nr1h3)] zebrafish strains, we measured post-prandial lipid excursion with live imaging in larvae and physiological methods in adults. We also conducted a long-term high-cholesterol dietary challenge in adults to examine the chronic effect of modulating nr1h3 gene dose on the development of hypercholesterolemia and hepatic lipid accumulation. Over-expression of Lxrα in the intestine delays the transport of ingested lipids in larvae, while deletion of Lxrα increases the rate of lipid transport. Pre-treating wildtype larvae with the liver-sparing Lxr agonist hyodeoxycholic acid also delayed the rate of intestinal lipid transport in larvae. In adult males, deletion of Lxrα accelerates intestinal transport of ingested lipids. Adult females showed higher plasma Lipoprotein lipase (Lpl) activity compared to males, and lower post-gavage blood triacylglycerol (TAG) excursion. Despite the sexually dimorphic effect on acute intestinal lipid handling, Tg(fabp2a:EGFP-nr1h3) adults of both sexes are protected from high cholesterol diet (HCD)-induced hepatic lipid accumulation, while nr1h3−/− mutants are sensitive to the effects of HCD challenge. These data indicate that intestinal Lxr activity dampens the pace of intestinal lipid transport cell-autonomously. Selective activation of intestinal Lxrα holds therapeutic promise.

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“…However, SR‐BI has also been shown to traffic in clathrin‐coated lipid vesicles after a lipid load , and we demonstrated that SR‐BI extracellular loop could bind mixed micelles . Finally, SR‐BI has recently been described as an intestinal lipid sensor , and it appeared to be a modulator of chylomicron secretion . These last results suggest that SR‐BI may actually promote lipid flux through the enterocyte and thus indirectly enhance vitamin E absorption.…”

Section: Vitamin E Transport Across the Enterocytementioning

confidence: 99%

Vitamin E intestinal absorption: Regulation of membrane transport across the enterocyte

Reboul

2018

IUBMB Life

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Vitamin E is an essential molecule for our development and health. It has long been thought that it was absorbed and transported through cellular membranes by a passive diffusion process. However, data obtained during the past 15 years showed that its absorption is actually mediated, at least in part, by cholesterol membrane transporters including the scavenger receptor class B type I (SR‐BI), CD36 molecule (CD36), NPC1‐like transporter 1 (NPC1L1), and ATP‐binding cassettes A1 and G1 (ABCA1 and ABCG1). This review focuses on the absorption process of vitamin E across the enterocyte. A special attention is given to the regulation of this process, including the possible competition with other fat‐soluble micronutrients, and the modulation of transporter expressions. Overall, recent results noticeably increased the comprehension of vitamin E intestinal transport, but additional investigations are still required to fully appreciate the mechanisms governing vitamin E bioavailability. © 2018 IUBMB Life, 71(4):416–423, 2019

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

Cited by 41 publications

References 45 publications

Morin, a novel liver X receptor α/β dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases

Morin, a novel liver X receptor α/β dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases

Role of Intestinal LXRα in Regulating Post-prandial Lipid Excursion and Diet-Induced Hypercholesterolemia and Hepatic Lipid Accumulation

Vitamin E intestinal absorption: Regulation of membrane transport across the enterocyte

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