Abstract: Non-alcoholic fatty liver disease (NAFLD) is gaining increasing recognition as a component of the epidemic of obesity world wide.NAFLD is the most common cause of liver dysfunction and affects close to 20 millions of patients in the USA.The spectrum of NAFLD ranges from simple fatty liver (hepatic steatosis), with benign prognosis, to a potentially progressive form, non-alcoholic steatohepatitis (NASH), which may lead to liver fibrosis and cirrhosis, resulting in increased morbidity and mortality.All features of the metabolic syndrome, including obesity, type 2 diabetes, arterial hypertension, and hyperlipidemia are associated with NAFLD/NASH.Excessive accumulation of TG in hepatocytes is the hallmark of NAFLD.Despite the existing correlation between fatty liver and insulin resistance it remains unclear whether insulin resistance causes the excessive accumulation of TG in liver or whether the increase in TG itself or of metabolic intermediates may play a causal role in the development of hepatic or systemic insulin resistance.Some studies have favored the concept that the accumulation of intra-hepatic lipids precedes the state of insulin resistance while others have shown that hepatic TG themselves are not toxic and may in fact protect the liver from lipotoxicity by buffering the accumulation of fatty acids.Such findings suggest that hepatic steatosis is not necessarily associated to insulin resistance.To explore the relationship between hepatic steatosis and insulin resistance, we have focused our studies on the function and regulation of the lipogenic transcription factor ChREBP in both mouse and human livers. SY1-2 Genetics of diabetesMarch 27 (Sat.)14:20-16:00 Room 5 SY 1-2-1Genetics of type 2 diabetes -Are we getting any closer?