More than 30% of New Zealanders are obese, and up to 90% of obese and 20% of non-obese suffer from non-alcoholic fatty liver disease (NAFLD). NAFLD is the accumulation of fat in the liver, and can progress to non-alcoholic steatohepatitis (NASH). Both of these diseases impair the function of the liver making suffers very ill, and are the leading causes of liver disease-related mortalities. Currently there are no effective treatment options for NAFLD and NASH. The reason for this is that we do not understand the mechanisms underlying excessive liver fat storage and damage. One of the earliest abnormalities associated with weight gain is an increase in the hormone insulin. This is required to maintain blood sugar levels, however it also promotes fat storage. In this proposal we will investigate whether high insulin levels act through the insulin receptor to drive NAFLD and NASH, and how this may be happening.