title: Lipid oxidation products in the pathogenesis of non-alcoholic steatohepatitis.
abstract: Non-alcoholic fatty liver disease (NAFLD) is the major public health challenge for hepatologists in the twenty-first century. NAFLD comprises a histological spectrum ranging from simple steatosis or fatty liver, to steatohepatitis, fibrosis, and cirrhosis. It can be categorized into two principal phenotypes: (1) non-alcoholic fatty liver (NAFL), and (2) non-alcoholic steatohepatitis (NASH). The mechanisms of NAFLD progression consist of lipid homeostasis alterations, redox unbalance, insulin resistance, and inflammation in the liver. Even though several studies show an association between the levels of lipid oxidation products and disease state, experimental evidence suggests that compounds such as reactive aldehydes and cholesterol oxidation products, in addition to representing hallmarks of hepatic oxidative damage, may behave as active players in liver dysfunction and the development of NAFLD. This review summarizes the processes that contribute to the metabolic alterations occurring in fatty liver that produce fatty acid and cholesterol oxidation products in NAFLD, with a focus on inflammation, the control of insulin signalling, and the transcription factors involved in lipid metabolism.
authors.affiliation: C.U.R.E. Centre for Liver Diseases Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia 71122, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bellanti
authors.affiliation: C.U.R.E. Centre for Liver Diseases Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia 71122, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Villani
authors.affiliation: C.U.R.E. Centre for Liver Diseases Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia 71122, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Facciorusso
authors.affiliation: C.U.R.E. Centre for Liver Diseases Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia 71122, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Vendemiale
authors.affiliation: C.U.R.E. Centre for Liver Diseases Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia 71122, Italy. Electronic address: gaetano.serviddio@unifg.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Serviddio
mesh_terms: D002784:Cholesterol / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D050612:Fatty Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000072376:Oxysterols / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D056918:Nuclear Receptor Coactivators; D000072376:Oxysterols; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol
keywords: Lipid metabolism; Lipid peroxidation; Non-alcoholic steatohepatitis; Oxysterols