Elevated circulating non-esterified fatty acids and bioactive lipid intermediates such as diacylglycerols and ceramides in liver and skeletal muscle are associated with disrupted insulin signaling and contribute directly to systemic insulin resistance, independent of total fat mass.

When fat cells release too many fatty acids due to poor insulin control and constant stress signals, those fatty acids flood into the liver and muscles. There, they turn into harmful molecules called diacylglycerols and ceramides, which block the insulin signal from telling cells to take up sugar. This happens even if a person is not overweight, because it is not the amount of fat stored, but the uncontrolled flow of fatty acids that breaks insulin function.