In order to examine these questions we examined: (1) whether transgenic mice with hepatic overexpression of human APOC3 (ApoC3Tg) are prone to develop nonalcoholic steatohepatitis (NASH); (2) whether NAFLD is associated with hepatic insulin resistance in this model; 3) the underlying mechanism by which these mice develop NAFLD; and (4) the cellular mechanisms by which NAFLD in these mice leads to hepatic insulin resistance. This evidence concerns the gene APOC3 and metabolic dysfunction-associated steatohepatitis.