Ceramides: A Cause of Insulin Resistance in Nonalcoholic Fatty Liver Disease in Both Murine Models and Humans

Patients with both NAFLD and the insulin resistance/metabolic syndrome ('Metabolic NAFLD') have an increased risk of developing type 2 diabetes and CVD. Triglycerides, contained within hepatic lipid droplets, themselves are, however, inert and not sufficient to cause insulin resistance. In numerous murine models, the liver accumulates triglycerides without becoming insulin resistant. Patients with NAFLD due to genetic variants such as the I148M variant in PNPLA3 ('PNPLA3 NAFLD'), are not insulin resistant and their risk of CVD is neutral (1).