Expert

Thibaut Bourgeois
Dec 11, 2020; 0:jlr.RA120000737v1-jlr.RA120000737
Research Articles

Aloïs Dusuel
Dec 9, 2020; 0:jlr.RA120000704v1-jlr.RA120000704
Research Articles

Bacterial lipopolysaccharides (LPSs or endotoxins) can bind most proteins of the lipid transfer/LPS-binding protein (LT/LBP) family in host organisms. The LPS-bound LT/LBP proteins then trigger either an LPS-induced proinflammatory cascade or LPS binding to lipoproteins that are involved in endotoxin inactivation and detoxification. Cholesteryl ester transfer protein (CETP) is an LT/LBP member, but its impact on LPS metabolism and sepsis outcome is unclear. Here, we performed fluorescent LPS transfer assays to assess the ability of CETP to bind and transfer LPS. The effects of intravenous (iv) infusion of purified LPS or polymicrobial infection (cecal ligation and puncture [CLP]) were compared in transgenic mice expressing human CETP and wild-type mice naturally having no CETP activity. CETP displayed no LPS transfer activity in vitro, but it tended to reduce biliary excretion of LPS in vivo. The CETP expression in mice was associated with significantly lower basal plasma lipid levels and with higher mortality rates in both models of endotoxemia and sepsis. Furthermore, CETPTg plasma modified cytokine production of macrophages in vitro. In conclusion, despite having no direct LPS binding and transfer property, human CETP worsens sepsis outcomes in mice by altering the protective effects of plasma lipoproteins against endotoxemia, inflammation, and infection.

Recent studies have highlighted an important role for lysophosphatidylcholine acyltransferase 3 (LPCAT3) in controlling the PUFA composition of cell membranes in the liver and intestine. In these organs, LPCAT3 critically supports cell membrane-associated processes such as lipid absorption or lipoprotein secretion. However, the role of LPCAT3 in macrophages remains controversial. Here, we investigated LPCAT3’s role in macrophages both in vitro and in vivo in mice with atherosclerosis and obesity. To accomplish this, we used the LysMCre strategy to develop a mouse model with conditional Lpcat3 deficiency in myeloid cells (Lpcat3KOMac). We observed that partial Lpcat3 deficiency (approx. 75% reduction) in macrophages alters the PUFA composition of all phospholipid (PL) subclasses, including phosphatidylinositols and phosphatidylserines. A reduced incorporation of C20 PUFAs (mainly arachidonic acid [AA]) into PLs was associated with a redistribution of these FAs toward other cellular lipids such as cholesteryl esters. Lpcat3 deficiency had no obvious impact on macrophage inflammatory response or endoplasmic reticulum (ER) stress; however, Lpcat3KOMac macrophages exhibited a reduction in cholesterol efflux in vitro. In vivo, myeloid Lpcat3 deficiency did not affect atherosclerosis development in LDL receptor deficient mouse (Ldlr-/-) mice. Lpcat3KOMac mice on a high-fat diet displayed a mild increase in hepatic steatosis associated with alterations in several liver metabolic pathways and in liver eicosanoid composition. We conclude that alterations in AA metabolism along with myeloid Lpcat3 deficiency may secondarily affect AA homeostasis in the whole liver, leading to metabolic disorders and triglyceride accumulation.

The way education media and policymakers frame education debates can have longer-term effects on how the public thinks about students, and which policies they are likely to support to improve students' learning.

Hundreds of disgruntled women and youths from Zamfara State, on Tuesday, took their protest to the headquarters of the Department of Security Services in Abuja, over heightened insecurity in the state. The aggrieved persons blamed the immediate-past governor of the state and now Minister of State for Defence, Bello Matawalle, for the heightened activities of

Gang violence has ravaged Haiti, causing thousands of civilian deaths, displacements, and violations of international humanitarian law. Turmoil is expected to escalate following the removal of Haitian Prime Minister Garry Conille from office on November 11. On November 10, the Haitian government announced plans to replace incumbent prime minister Conille, with entrepreneur and former senate […]

Extreme weather and a growing population is driving a food security crisis. What can we do to break the vicious cycle of carbon emissions, climate change and soaring food costs – or is it already too late?

Fibres in wet wipes and clothes often make their way into soil - and natural versions could be more damaging than synthetic ones

Extreme weather and a growing population is driving a food security crisis. What can we do to break the vicious cycle of carbon emissions, climate change and soaring food costs – or is it already too late?

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Category: Health News
Created: 8/26/2013 12:36:00 PM
Last Editorial Review: 8/27/2013 12:00:00 AM

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Category: Health News
Created: 8/21/2020 12:00:00 AM
Last Editorial Review: 8/24/2020 12:00:00 AM

Title: Longer, Worse COVID Leaves Stronger Antibodies: Study
Category: Health News
Created: 8/23/2021 12:00:00 AM
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Title: Menopause Might Worsen Jaw Pain in Women
Category: Health News
Created: 5/17/2022 12:00:00 AM
Last Editorial Review: 5/17/2022 12:00:00 AM

Title: Who Fares Worse After Multiple Sclerosis Strikes?
Category: Health News
Created: 8/11/2022 12:00:00 AM
Last Editorial Review: 8/12/2022 12:00:00 AM

Using more training data and computational power is meant to make AIs more reliable, but tests suggest large language models actually get less reliable as they grow

Via Rail's service standards have eroded substantially over the last decade, with many more trains arriving late.

Fibres in wet wipes and clothes often make their way into soil - and natural versions could be more damaging than synthetic ones