title: The relationship between apoptosis and non-alcoholic fatty liver disease: an evolutionary cornerstone turned pathogenic.
abstract: The data currently available favor a model for the pathogenesis of non-alcoholic fatty liver disease that is based on an apparent sequential relationship of intrahepatic apoptosis, inflammation and fibrogenesis. Based on both hepatic and peripheral insulin resistance, the hepatocellular accumulation of triglycerides, termed steatosis, initially leads to an altered metabolism of glucose and free fatty acids in the liver. In response, increased expression of death receptors in simple steatosis enhances the hepatocytes' susceptibility for pro-apoptotic stimuli, thus eliciting excessive hepatocyte apoptosis and inflammation. Evidence indicates that these processes, if prolonged, activate both hepatic stellate and Kupffer cells, thus leading to a vicious circle in which apoptosis, inflammation, cellular activation, and collagen deposition are upregulated even further.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. Ali.Canbay@Uni-Essen.de
authors.forename: A
authors.initials: A
authors.lastname: Canbay
authors.forename: R K
authors.initials: RK
authors.lastname: Gieseler
authors.forename: G J
authors.initials: GJ
authors.lastname: Gores
authors.forename: G
authors.initials: G
authors.lastname: Gerken
mesh_terms: D000818:Animals; D017209:Apoptosis; D005075:Biological Evolution; D001786:Blood Glucose / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000473:pathology*; D006505:Hepatitis / Q000473:pathology; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007728:Kupffer Cells / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation / Q000502:physiology
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D018124:Receptors, Tumor Necrosis Factor; D014280:Triglycerides; D003094:Collagen