ICAN BioCell Human Liver Biology

29/04/2020

Novel defatting strategies reduce lipid accumulation in primary human culture models of liver steatosis

Liver transplantation (LT) is now the recognised treatment for end-stage chronic liver disease. There is currently a shortage of organs and ‘marginal’ grafts, particularly steatotic (fatty liver) grafts, are increasingly being used to try to limit this shortage. Steatosis is the main reason why liver transplants are rejected by TH teams, as it is responsible for liver dysfunction after transplantation. The use of steatotic grafts could go some way to reducing the shortage of grafts currently affecting patients waiting for TH. Our strategy is to treat these ‘candidate’ grafts prior to implantation using normo-thermal perfusion (physiological temperature 37°C), which would improve tolerance to ischaemia and extract lipid vacuoles from the hepatocytes. Our ‘degreasing’ method involves acting directly on the excessive accumulation of lipids. In this study, we devised a ‘degreasing’ cocktail to remove the lipids stored in steatotic hepatocytes. To do this, we created a cocktail composed of molecules designed to activate each stage of intra-hepatocyte lipid metabolism until the lipids are removed from the cell.

21/11/2019

Inhibition of receptor-interacting protein kinase-1 improves experimental non-alcoholic fatty liver disease

Hepatic steatosis is the accumulation of fat in the liver. Steatosis is very common(25% of the French population is affected) and is very often associated with overweight and type 2 diabetes. Often asymptomatic and of no consequence, the accumulation of fat is responsible in 30% of cases for inflammatory lesions of the liver (non-alcoholic steatohepatitis or NASH), which can lead to non-alcoholic cirrhosis and liver cancer. The inflammation and death of liver cells in NASH is initially compensated for by the liver’s regenerative capacity. However, in the context of chronic liver damage, as observed in NASH, these healing capacities are deleterious and contribute to the destruction of the liver (fibrosis). One of our current research objectives is to identify the mechanisms behind inflammation and cell death in NASH in order to propose effective treatments. Our team has recently demonstrated, through work in mice and on human liver cells , that blocking cell death in NASH reduces inflammation and abnormal scarring of the liver and limits the accumulation of fat in the liver.