We are studying the role of Lipoproteins and lipid molecules, as well as the impact of lipid exchanges in the modulation of inflammation with applications in chronic inflammation (atherosclerosis) and acute inflammatory diseases including sepsis.
Main investigators :
Lipopolysaccharides (LPS) bind and activate Toll like receptor 4 at the surface of immune cells, leading to the release of pro-inflammatory cytokines and to inflammation. Alternatively, bacterial blebs forming large LPS aggregates can be disrupted and molecular transfer of LPS towards lipoproteins can occur. It results in its neutralization and elimination back to the liver, namely the reverse LPS transport pathway (RLT). Recent observations suggest that PLTP and CETP, as members of the lipid transfer/lipopolysaccharide binding protein gene family play a driving role in RLT, thus modulating inflammation and innate immunity.
Recent publications :
Main investigators :
Some evidence indicates that LPS molecules are removed from the body through biliary excretion as the final step of the reverse LPS transport pathway. While some previous works have documented the biophysical interaction of endotoxins with purified bile acids, its pathophysiological consequence in terms of proinflammatory capacity of LPS is not completely clear. We aim at better understanding the link between bile acid metabolism and neutralization/detoxification of LPS.
Main investigators :
The incidence of severe sepsis and septic shock is about 15% of all admission in ICU and the hospital mortality is 25% and 49%, respectively. Despite significant advances in our understanding of the pathophysiology of severe sepsis and septic shock, attempts to translate these finding into novel treatments and improved outcomes for patients have been disappointing. One main objective of the Lipness team is to determine to which extent LPS neutralization and elimination may constitute a new and relevant approach to improve clinical outcome of septic shock.
Recent publication :
Main investigator :
In healthy subjects, moderate endotoxemia has been associated with increased insulin sensitivity on the short term whereas insulin resistance can occur at later time points. We have recently shown that LPS is able to increase circulating levels of glucagon-like peptide-1 (GLP-1), an incretin involved in insulin secretion stimulated by glucose (GSIS).
Recent publication :
Main investigators :
Phospholipids are continuously remodeled through deacylation and reacylation by the opposite actions of phospholipase A2, and lysophospholipid acyl-transferases (LPLATs). LPLATs affect both the PUFA content of phospholipids and the availability of free fatty acids such as arachidonic acid used for eicosanoid synthesis. By using specific mouse models and samples from human patients, we assess the impact of phospholipid and fatty acid metabolism in myeloid cells on inflammation and atherosclerosis development.
Recent publications :
Main investigators :
Mitophagy is a mitochondria-dedicated autophagy allowing clearance of damaged mitochondria in the cell. Our investigations aim to unravel the signaling pathway resulting to the inhibition of mitophagy by LPS and IFNγ in macrophages. We investigate whether this inhibition of mitophagy occurs in macrophages and polynuclear neutrophils in the context of bacterial infection such as sepsis or experimental models of pneumonia and whether modulation of mitophagy may affect the inflammatory and bactericidal responses.
Recent publications :
Main investigators :
Metabolic syndrome (MS) is tightly associated with low grade inflammation, endotoxemia and intestinal microbiota modulation. A decrease of the n-6/n-3 ratio by n-3 PUFA-enriched diets can exert beneficial effects during obesity and insulin-resistance in rodent models and microbiome changes could improve intestinal integrity and reduce hepatic and systemic inflammation. We recently showed (by microbiome transplantation) that endogenously synthesized n-3 PUFAs exert beneficial effects during MS. We are now focused on 1) evaluating the effects of fatty acids on intestinal barrier 2) deciphering molecular mechanisms involved in the relative contribution of n-3-enriched microbiota in the prevention of MS. A special attention is paid on the mucus layer in terms of strengthening the intestinal barrier integrity by n-3 fatty acids.
Recent publication :
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Deciphering the role of lipoproteins in the Reverse Lipopolysaccharide Transport pathway