Role of lipogenesis and lipid desaturases in non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathological change characterized by the accumulation of triacylglycerol (TG) in hepatic lipid droplets (LD). NAFLD can range from a simple steatosis to Non-alcoholic steatohepatitis (NASH) characterized by hepatic injury, inflammation, and eventually fibrosis. NAFLD can also be associated with insulin resistance (IR), ER stress, oxidative stress and inflammation. The cause of NAFLD is due to modification of various metabolic pathways including increased fatty acid (FA) uptake and/or reduced FA oxidation, decreased VLDL secretion and increased de novo lipogenesis (DNL). NAFLD is often observed in obese patients where energy is in excess and energy expenditure is low. In these conditions, most of carbohydrates are converted into TG through DNL. We aim here to present the most recent studies demonstrating the key role of DNL in NAFLD development. A special focus will be made on desaturases especially the stearoyl CoA desaturase 1, a central enzyme implicated in fatty liver disease as well as on the delta 5 and delta 6 desaturases, two enzymes involved in the synthesis of omega 3 and omega 6 fatty acids.