Steatosis in the Liver

Accumulation of triacylglycerols within the cytoplasm of hepatocytes to the degree that lipid droplets are visible microscopically is called liver steatosis. Most commonly, it occurs when there is an imbalance between the delivery or synthesis of fatty acids in the liver and their disposal through oxidative pathways or secretion into the blood as a component of triacylglycerols in very low density lipoprotein. This disorder is called nonalcoholic fatty liver disease (NAFLD) in the absence of alcoholic abuse and viral hepatitis, and it is often associated with insulin resistance, obesity and type 2 diabetes. Also, liver steatosis can be induced by many other causes including excessive alcohol consumption, infection with genotype 3 hepatitis C virus and certain medications. Whereas hepatic triacylglycerol accumulation was once considered the ultimate effector of hepatic lipotoxicity, triacylglycerols per se are quite inert and do not induce insulin resistance or cellular injury. Rather, lipotoxic injury in the liver appears to be mediated by the global ongoing fatty acid enrichment in the liver, paralleling the development of insulin resistance. A considerable number of fatty acid metabolites may be responsible for hepatic lipotoxicity and liver injury. Additional key contributors include hepatic cytosolic lipases and the "lipophagy" of lipid droplets, as sources of hepatic fatty acids. The specific origin of the lipids, mainly triacylglycerols, accumulating in liver has been unraveled by recent kinetic studies, and identifying the origin of the accumulated triacylglycerols in the liver of patients with NAFLD may direct the prevention and treatment of this condition.