The LXR agonist T0901317 promotes the reverse cholesterol transport from macrophages by increasing plasma efflux potential

Zanotti, Ilaria; Potì, Francesco; Pedrelli, Matteo; Favari, Elda; Moleri, Elsa; Franceschini, Guido; Calabresi, Laura; Bernini, Franco

doi:10.1194/jlr.m700254-jlr200

Cited by 55 publications

(62 citation statements)

References 32 publications

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“…On the other hand, the treatment of high dose TO901317 (10 μmol/L) could increase the extracellular cholesterol accumulation. It was predicted that the LXR activation increases the cholesterol efflux from the hepatocytes, and a similar result reported by Zanotti et al, showed that in vivo stimulation of LXR by TO901317 increase the efflux of cholesterol from peritoneal macrophages (Zanotti et al, 2008). Another previous study showed that LXR agonist TO901317 has been shown to induce the expression of ABCA1 and other LXR-responsive genes.…”

Section: General Remarkssupporting

confidence: 62%

Effect of a Synthetic Liver X Receptor Agonist TO901317 on Cholesterol Concentration in Goose Primary Hepatocytes

Han

Liu

et al. 2014

Italian Journal of Animal Science

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In this study, we investigated the role of liver X receptor (LXR) in regulating cholesterol concentration in goose primary hepatocytes. Intracellular and extracellular cholesterol concentration, mRNA expression levels of genes related to phosphatidylinositol 3-kinase (PI3K) pathway, sterol regulatory element-binding protein 2 (SREBP-2), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) were measured in primary goose hepatocytes. We found that the intracellular cholesterol concentration showed an uptrend manner when the TO901317 concentration was under 1 μmol/L; compared with 1 μmol/L TO901317, 10 μmol/L TO901317 had an inhibiting effect (P<0.05). The regulation mode of SREBP-2 and HMGR gene expression is similar with that of intracellular cholesterol concentration. These data suggested that LXR activation may stimulate the cholesterol biosynthesis by activating expression of SREBP-2 and HMGR. Interestingly, the mRNA levels of genes related with PI3K pathway increased in the presence of TO901317, which suggested that LXR activation could promote PI3K signalling activity.

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Section: General Remarkssupporting

confidence: 62%

Effect of a Synthetic Liver X Receptor Agonist TO901317 on Cholesterol Concentration in Goose Primary Hepatocytes

Han

Liu

et al. 2014

Italian Journal of Animal Science

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“…Feces samples were collected at 24 and 48 hours after the injection of radiolabeled cells and extracted by the method of Bligh and Dyer. 13,22 […”

Section: Macrophage Rct In Vivomentioning

confidence: 99%

“…Plasma was isolated by low-speed centrifugation and stored at Ϫ80°C until use. Livers were extracted using the method of Bligh and Dyer 13,22 and counted by liquid scintillation addition. Feces samples were collected at 24 and 48 hours after the injection of radiolabeled cells and extracted by the method of Bligh and Dyer.…”

Section: Macrophage Rct In Vivomentioning

confidence: 99%

“…13 The relative content of pre-␤ HDL was calculated using computer software (Bio-Rad Multi-Analyst/PC Software) and expressed as percentage of total apoA-I.…”

Section: D Gel Electrophoresismentioning

confidence: 99%

“…Macrophage RCT can be estimated with a radioisotope-based assay, whose application has been useful for genetic and pharmacological investigations on this process. [12][13][14][15][16] HDL are the major players of cholesterol efflux and RCT. 17 HDL represent a heterogeneous class of particles whose composition influences the capacity to act as efficient lipid acceptors: large phospholipid-enriched HDL (␣-HDL) specifically exchange lipids with scavenger receptor class B type I (SR-BI) 18 and ATP-binding cassette G1 19 or through passive diffusion.…”

mentioning

confidence: 99%

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Macrophage, But Not Systemic, Apolipoprotein E Is Necessary for Macrophage Reverse Cholesterol Transport In Vivo

Zanotti

Pedrelli

Potì

et al. 2011

ATVB

Self Cite

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Objective-To assess the role of apolipoprotein (apo) E in macrophage reverse cholesterol transport (RCT) in vivo. Methods and Results-ApoE exerts an antiatherosclerotic activity by regulating lipoprotein metabolism and promoting cell cholesterol efflux. We discriminated between macrophage and systemic apoE contribution using an assay of macrophage RCT in mice. The complete absence of apoE lead to an overall impairment of the process and, similarly, the absence of apoE exclusively in macrophages resulted in the reduction of cholesterol mobilization from macrophages to plasma, liver, and feces. Conversely, expression of apoE in macrophages is sufficient to promote normal RCT even in apoE-deficient mice. The mechanisms accounting for these results were investigated by evaluating the first step of RCT (ie, cholesterol efflux from cells). Macrophages isolated from apoE-deficient mice showed a reduced ability to release cholesterol into the culture medium, whereas the apoB-depleted plasma from apoE-deficient and healthy mice possessed a similar capacity to promote cellular lipid release from cultured macrophages. Conclusion-Our data demonstrate, for the first time to our knowledge, that apoE significantly contributes to macrophage RCT in vivo and that this role is fully attributable to apoE expressed in macrophages. A polipoprotein E (apoE) is a structural component of several lipoproteins, including very-low-density lipoproteins (LDLs) and their remnants, chylomicron remnants, and high-density lipoproteins (HDL). 1 ApoE is predominantly synthesized by the liver and accomplishes its physiological role by driving the hepatic clearance of the lipoproteins on which it resides through binding with very LDL and chylomicron-remnant receptors 2 and inhibiting triglyceride lipolysis. 3 Altogether, these activities contribute to the regulation of circulating lipoprotein levels. Several population studies 3-5 associated apoE defects with lipoprotein disorders and increased cardiovascular risk, thus revealing the key role played in atheroprotection. This beneficial activity was further demonstrated by the generation of mice lacking the apoE gene, characterized by hypercholesterolemia and abnormal lipid deposition in the proximal aorta and liver, even when receiving a normal chow diet. 6,7 Beyond the influence on lipoprotein metabolism, apoE atheroprotective activity is also related to the promotion of cholesterol efflux from macrophages. 8,9 Cholesterol efflux is the first ratelimiting step of reverse cholesterol transport (RCT), the process by which excess cholesterol is delivered from peripheral tissues to the liver for final excretion into the feces. 10 Macrophage is the primary cell type overloaded with cholesterol within atherosclerotic lesions, and this cholesterol pool is the most important for atherosclerosis development and progression. 11 Thus, the RCT that involves macrophage-derived cholesterol became fundamental concerning atheroprotection. Macrophage RCT can be estimated with a radioisotope-based assay, whose appli...

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Overview of the Measurement of Lipids and Lipoproteins in Mice

Tailleux

Staels

2011

CP Mouse Biology

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Experimental mouse models are widely used for preclinical research on dyslipidemia, atherosclerosis, and cardiometabolic diseases. This unit reports the most commonly used biochemical analysis methods available to determine the lipid and lipoprotein phenotype in the mouse. The discussed methods include: the qualitative and quantitative analysis of lipids, apolipoproteins, and lipoproteins (with a specific emphasis on species-specificities of mice and humans), and the activity assay of major enzymes involved in lipoprotein remodeling (LCAT, PLTP, and LPL). The unit also discusses the most frequently used functional tests to analyze lipid/lipoprotein metabolism in vivo, including triglyceride metabolism, reverse cholesterol transport, intestinal lipid absorption, and secretion. Curr. Protoc. Mouse Biol. 1:265-277 © 2011 by John Wiley & Sons, Inc.

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The LXR agonist T0901317 promotes the reverse cholesterol transport from macrophages by increasing plasma efflux potential

Cited by 55 publications

References 32 publications

Effect of a Synthetic Liver X Receptor Agonist TO901317 on Cholesterol Concentration in Goose Primary Hepatocytes

Effect of a Synthetic Liver X Receptor Agonist TO901317 on Cholesterol Concentration in Goose Primary Hepatocytes

Macrophage, But Not Systemic, Apolipoprotein E Is Necessary for Macrophage Reverse Cholesterol Transport In Vivo

Overview of the Measurement of Lipids and Lipoproteins in Mice

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