Lipids play Jekyll and Hyde in the liver. On the one hand, the
lipid-laden status of hepatic stellate cells is a hallmark of healthy liver. On the other hand, the opposite is true for
lipid-laden hepatocytes-they obstruct liver function. Neglected
lipid accumulation in hepatocytes can progress into hepatic
fibrosis, a condition induced by the activation of stellate cells. In their resting state, these cells store substantial quantities of fat-soluble
vitamin A (
retinyl esters) in large lipid droplets. During activation, these
lipid organelles are gradually degraded. Hence, treatment of
fatty liver disease is treading a tightrope-unsophisticated targeting of hepatic
lipid accumulation might trigger problematic side effects on stellate cells. Therefore, it is of great importance to gain more insight into the highly dynamic lipid metabolism of hepatocytes and stellate cells in both quiescent and activated states. In this review, part of the special issue entitled "Cellular and Molecular Mechanisms underlying the Pathogenesis of Hepatic
Fibrosis 2020", we discuss current and highly versatile aspects of neutral lipid metabolism in the pathogenesis of
non-alcoholic fatty liver disease (
NAFLD).