Non-alcoholic fatty liver disease (NAFLD) is a common and potentially serious condition often associated with obesity, type-2 diabetes and hyperlipidemia. In response to nutritional and hormonal signals, the liver regulates several features of lipid metabolism including free fatty acid (FFA) β-oxidation, lipogenesis and lipoprotein uptake and secretion. In fact, ectopic accumulation of fat in the liver is a combined result of increased hepatic lipogenesis and decreased FFA β-oxidation as well as transport of FFAs to the liver from extra-hepatic tissues.

 

Recent findings have revealed a significant role of endocannabinoids and CB1 receptor in the pathogenesis of fatty liver, yet the exact molecular mechanisms underlying this phenomenon remain obscure. Therefore, using a combination of in vitro cell biological approaches, state-of-the-art mouse genetics and novel pharmacological tools, we plan to delineate the key signaling factors involved in mediating the role of hepatic CB1 receptors in obesity-induced hepatic steatosis. Once identified, they may provide new molecular targets for therapeutic interventions aimed to attenuate/reverse NAFLD.