Impact of environmental chemicals on the mechanisms of disease progression of liver steatosis – STEATOX

Several studies are pointing out that western lifestyle (high-fat diet, alcohol consumption, cigarette smoking) cannot explain by itself the increasing incidence of cancers, especially of hepatocellular carcinoma (HCC). Obesity, which increased from 8 % in 1997 to 14 % in 2009 in the French population has become a new risk factor for HCC. Besides obesity, 31.9 % of the population is overweight. The liver is an organ that can suffer from the excess of body fat mass by developing steatosis, i.e. lipid accumulation in the liver, mainly as triglycerides. Though fatty liver is by itself a benign liver lesion in the short-term, it can evolve in the long-term towards other forms of chronic liver diseases that can be severe, including non alcoholic steatohepatitis, cirrhosis and HCC. In this context, there is an urgent social need to identify the factors (possibly related to our environment) involved in this evolution in individuals bearing metabolic diseases in order to reduce the incidence of liver pathologies leading to HCC. The complete elimination of exposure to environmental carcinogens, synthetic or natural, being technically unfeasible, exposure of humans to toxic chemicals is inevitable, particularly due to contamination of food. Hence, there is a need to develop studies on the biological and toxicological effects of these contaminants to increase our knowledge on their action mechanisms; notably in interaction with lifestyle and considering pre-existing factors such as metabolic diseases. One of the key aspirations of mixture toxicology has always been to anticipate quantitatively the effects of mixtures of chemicals from knowledge about the toxicity of its individual components. To our knowledge, nothing is known about the impact of such mixtures on the development of hepatic pathologies in weakened populations. Our project is therefore aimed at analyzing the effects of environmental contaminants suspected of inducing liver damage in human, each in binary combination with an important lifestyle factor, that is alcohol consumption, considering the population bearing hepatic steatosis.