Axis 3, Team 3 | Analysis of the impact of contaminants on the pathologic progression of liver steatosis (fatty liver)

Biological and toxicological effects of chemical contaminants in severe liver disease.

This axis is devoted to the study of biological and toxicological effects of chemical contaminants in the context of populations considered at risk for the genesis of severe liver disease. Thus, the goal of this axis is to determine if environmental contaminants could play a role in the pathologic progression of steatosis using in vitro and in vivo models. In addition, another population at risk is targeted: alcohol consumers, considering this lifestyle factor as an important and well-known hepatic toxicant.

Membrane remodeling and signaling are studied following treatment with PAHs or phthalates in combination or not with ethanol or dietary lipids. Both in vitro (rodent or human cell lines: hepatocytes, endothelial cells, blood cells) and in vivo models (Zebrafish larvae) are used. A special focus is brought to the impact of pollutant exposure on the disease progression of liver steatosis (ANR CESA “STEATOX” project). Various factors involved in membrane remodeling (reactive metabolites, alteration of lipid metabolism enzymes, oxidative stress, ionic homeostasis [H+ and Ca2+]) are investigated. In addition, we explore the connection between the modulation of the plasma membrane physicochemical parameters and the intra- and extracellular signaling triggering cell fate. Our project is performed notably thanks to our “Membrane & Stress” Plateau.