Taken together, these data demonstrate that differences in the intracellular compartmentation of sn-1,2-DAGs in the lipid droplet versus plasma membrane explain the dissociation of NAFLD and lipid-induced hepatic insulin resistance in young L-Mttp−/− mice as well as the development of lipid-induced hepatic insulin resistance in aged L-Mttp−/− mice. This evidence concerns the gene MT-TP and metabolic dysfunction-associated steatotic liver disease.