scholarly journals Revisiting the Role of LXRs in PUFA Metabolism and Phospholipid Homeostasis

2019 ◽  
Vol 20 (15) ◽  
pp. 3787 ◽  
Author(s):  
Antoine Jalil ◽  
Thibaut Bourgeois ◽  
Louise Ménégaut ◽  
Laurent Lagrost ◽  
Charles Thomas ◽  
...  
Keyword(s):  
Phospholipid Metabolism ◽  
Transfer Protein ◽  
Lipid Species ◽  
Pufa Composition ◽  
Phospholipid Transfer ◽  
X Receptors ◽  
Lxr Agonists ◽  
Pufa Metabolism

Liver X receptors (LXRs) play a pivotal role in fatty acid (FA) metabolism. So far, the lipogenic consequences of in vivo LXR activation, as characterized by a major hepatic steatosis, has constituted a limitation to the clinical development of pharmacological LXR agonists. However, recent studies provided a different perspective. Beyond the quantitative accumulation of FA, it appears that LXRs induce qualitative changes in the FA profile and in the distribution of FAs among cellular lipid species. Thus, LXRs activate the production of polyunsaturated fatty acids (PUFAs) and their distribution into phospholipids via the control of FA desaturases, FA elongases, lysophosphatidylcholine acyltransferase (LPCAT3), and phospholipid transfer protein (PLTP). Therefore, LXRs control, in a dynamic manner, the PUFA composition and the physicochemical properties of cell membranes as well as the release of PUFA-derived lipid mediators. Recent studies suggest that modulation of PUFA and phospholipid metabolism by LXRs are involved in the control of lipogenesis and lipoprotein secretion by the liver. In myeloid cells, the interplay between LXR and PUFA metabolism affects the inflammatory response. Revisiting the complex role of LXRs in FA metabolism may open new opportunities for the development of LXR modulators in the field of cardiometabolic diseases.

scholarly journals Intra-Abdominal Lipopolysaccharide Clearance and Inactivation in Peritonitis: Key Roles for Lipoproteins and the Phospholipid Transfer Protein

2021 ◽  
Vol 12 ◽  
Author(s):  
Maxime Nguyen ◽  
Gaëtan Pallot ◽  
Antoine Jalil ◽  
Annabelle Tavernier ◽  
Aloïs Dusuel ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Central Compartment ◽  
Phospholipid Transfer Protein ◽  
Wild Type ◽  
Transfer Protein ◽  
Early Arrival ◽  
Phospholipid Transfer ◽  
Pass Through ◽  
Lps Binding

IntroductionDuring peritonitis, lipopolysaccharides (LPS) cross the peritoneum and pass through the liver before reaching the central compartment. The aim of the present study was to investigate the role of lipoproteins and phospholipid transfer protein (PLTP) in the early stages of LPS detoxification.Material and MethodsPeritonitis was induced by intra-peritoneal injection of LPS in mice. We analyzed peritoneal fluid, portal and central blood. Lipoprotein fractions were obtained by ultracentrifugation and fast protein liquid chromatography. LPS concentration and activity were measured by liquid chromatography coupled with mass spectrometry and limulus amoebocyte lysate. Wild-type mice were compared to mice knocked out for PLTP.ResultsIn mice expressing PLTP, LPS was able to bind to HDL in the peritoneal compartment, and this was maintained in plasma from portal and central blood. A hepatic first-pass effect of HDL-bound LPS was observed in wild-type mice. LPS binding to HDL resulted in an early arrival of inactive LPS in the central blood of wild-type mice.ConclusionPLTP promotes LPS peritoneal clearance and neutralization in a model of peritonitis. This mechanism involves the early binding of LPS to lipoproteins inside the peritoneal cavity, which promotes LPS translocation through the peritoneum and its uptake by the liver.

P4-085: The role of liver X receptor (LXR) agonists in modulating Aβ levels In vitro and In vivo

2006 ◽  
Vol 2 ◽  
pp. S539-S539
Author(s):  
David R. Riddell ◽  
Hua Zhou ◽  
Yolanda Kirksey ◽  
Kevin Atchison ◽  
Suzan Aschmies ◽  
...  
Keyword(s):  
Liver X Receptor ◽  
Lxr Agonists

scholarly journals α-Tocomonoenol Is Bioavailable in Mice and May Partly Be Regulated by the Function of the Hepatic α-Tocopherol Transfer Protein

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4803
Author(s):  
Andrea Irías-Mata ◽  
Nadine Sus ◽  
Maria-Lena Hug ◽  
Marco Müller ◽  
Walter Vetter ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Room Temperature ◽  
Systemic Circulation ◽  
Future Research ◽  
Wild Type ◽  
Transfer Protein ◽  
In Vivo Experiments ◽  
And Storage

Tocomonoenols are vitamin E derivatives present in foods with a single double bond at carbon 11’ in the sidechain. The α-tocopherol transfer protein (TTP) is required for the maintenance of normal α-tocopherol (αT) concentrations. Its role in the tissue distribution of α-11′-tocomonoenol (αT1) is unknown. We investigated the tissue distribution of αT1 and αT in wild-type (TTP+/+) and TTP knockout (TTP−/−) mice fed diets with either αT or αT1 for two weeks. αT1 was only found in blood, not tissues. αT concentrations in TTP+/+ mice were in the order of adipose tissue > brain > heart > spleen > lungs > kidneys > small intestine > liver. Loss of TTP function depleted αT in all tissues. αT1, contrary to αT, was still present in the blood of TTP−/− mice (16% of αT1 in TTP+/+). Autoclaving and storage at room temperature reduced αT and αT1 in experimental diets. In conclusion, αT1 is bioavailable, reaches the blood in mice, and may not entirely depend on TTP function for secretion into the systemic circulation. However, due to instability of the test compounds in the experimental diets, further in vivo experiments are required to clarify the role of TTP in αT1 secretion. Future research should consider compound stability during autoclaving of rodent feed.

Liver X Receptor Activation Impairs Neutrophil Functions and Aggravates Sepsis

2019 ◽  
Vol 221 (9) ◽  
pp. 1542-1553 ◽  
Author(s):  
Fabrício O Souto ◽  
Fernanda V S Castanheira ◽  
Silvia C Trevelin ◽  
Braulio H F Lima ◽  
Guilherme Cesar Martelossi Cebinelli ◽  
...  
Keyword(s):  
Multiorgan Failure ◽  
Bacterial Load ◽  
Cecal Ligation ◽  
Neutrophil Infiltration ◽  
Receptor Activation ◽  
Messenger Ribonucleic Acid ◽  
X Receptors ◽  
Lxr Agonists

Abstract Background Liver X receptors (LXRs) are nuclear receptors activated by oxidized lipids and were previously implicated in several metabolic development and inflammatory disorders. Although neutrophils express both LXR-α and LXR-β, the consequences of their activation, particularly during sepsis, remain unknown. Methods We used the model of cecal ligation and puncture (CLP) to investigate the role of LXR activation during sepsis. Results In this study, we verified that LXR activation reduces neutrophil chemotactic and killing abilities in vitro. Mice treated with LXR agonists showed higher sepsis-induced mortality, which could be associated with reduced neutrophil infiltration at the infectious foci, increased bacteremia, systemic inflammatory response, and multiorgan failure. In contrast, septic mice treated with LXR antagonist showed increased number of neutrophils in the peritoneal cavity, reduced bacterial load, and multiorgan dysfunction. More important, neutrophils from septic patients showed increased ABCA1 messenger ribonucleic acid levels (a marker of LXR activation) and impaired chemotactic response toward CXCL8 compared with cells from healthy individuals. Conclusions Therefore, our findings suggest that LXR activation impairs neutrophil functions, which might contribute to poor sepsis outcome.

scholarly journals Cigarette smoke extract induces the epithelial-to-mesenchymal transition via the PLTP/TGF-β1/Smad2 pathway in RLE-6TN cells

2017 ◽  
Vol 6 (2) ◽  
pp. 215-222 ◽  
Author(s):  
Hong Chen ◽  
Feng-ping Wu ◽  
Yong-zhen Yang ◽  
Xiu-ying Yu ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Epithelial To Mesenchymal Transition ◽  
Cigarette Smoke Extract ◽  
Phospholipid Transfer Protein ◽  
Mesenchymal Transition ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Tgf Β1

Aim: The role of phospholipid transfer protein (PLTP) in the pathogenesis of the cigarette smoke extract (CSE)-induced epithelial-to-mesenchymal transition (EMT) has not been well described.

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