Obésité et syndrome métabolique
Obesity and the metabolic syndrome (MetS) are considered as key etiological conditions that predispose to the development of insulin resistance, steatosis (NAFLD), inflammation and fibrosis (NASH) in the liver, as wells as progression of these disorders towards cirrhosis and cancer. In this regard, obesity and metabolic diseases have reached pandemic proportions and incidence of NAFLD/NASH/fibrosis is expected to dramatically increase in the future, likely becoming the most common hepatic diseases worldwide. In the context of these liver pathologies, accumulating evidence indicates that PTEN, a protein/lipid phosphatase with potent tumor suppressor activity, is a major dysregulated cellular factor contributing to the development of a broad spectrum of hepatic disorders associated with obesity and MetS. In particular, circulating fatty acids and inflammatory cytokines, which are usually elevated with obesity/MetS, downregulate PTEN expression/activity in hepatocyte thereby altering insulin sensitivity of the liver and promoting in this organ the development of NAFLD/NASH/fibrosis and cancer. However the molecular mechanisms altered by PTEN deficiency in hepatocytes and promoting these hepatic disorders are still obscur.