Fatty liver and lipotoxicity.
Fatty liver disease comprises a spectrum ranging from simple steatosis to steatohepatitis which can progress to liver cirrhosis and hepatocellular cancer. Hepatic lipotoxicity may ensue when the hepatic capacity to utilize, store and export fatty acids (FA) as triglycerides is overwhelmed. Additional mechanisms of hepatic lipotoxicity include abnormal FA oxidation with formation of reactive oxygen species, disturbances in cellular membrane FA and phospholipid composition, alterations of cholesterol content and ceramide signalling. Lipotoxicity is a key factor for the progression of fatty liver disease by inducing hepatocellular death, activating Kupffer cells and an inflammatory response, impairing hepatic insulin signalling resulting in insulin resistance, and activation of a fibrogenic response in hepatic stellate cells that can ultimately lead to cirrhosis. Therefore, the concept of hepatic lipotoxicity should be considered in future therapeutic concepts for fatty liver disease.
Trauner
Michael
M
Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. michael.trauner@meduni-graz.at
Arrese
Marco
M
Wagner
Martin
M
D000818:Animals; D018450:Disease Progression; D005227:Fatty Acids / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D008113:Liver Neoplasms / Q000378:metabolism; D008954:Models, Biological
D005227:Fatty Acids