Triglycerides in Nonalcoholic Fatty Liver Disease: Guilty Until Proven Innocent

End-stage liver disease (ESLD) is a rare but often fatal complication of nonalcoholic fatty liver disease (NAFLD). In NAFLD, insulin resistance, which is clinically defined as the impairment of insulin's ability to maintain glucose homeostasis, is associated with perturbations in insulin action that promote triglyceride accumulation, such as increasing de novo lipogenesis. However, the key step in the development of ESLD is not the accumulation of triglycerides, but hepatocyte injury. Whether and how triglycerides promote hepatocyte injury remains unclear. Consequently, it is difficult to predict whether drugs designed to reduce hepatic triglycerides will prevent the most important complications of NAFLD.