title: Effects of dietary fatty acids and cholesterol excess on liver injury: A lipidomic approach.
abstract: Lipid accumulation is the hallmark of Non-alcoholic Fatty Liver Disease (NAFLD) and has been suggested to play a role in promoting fatty liver inflammation. Previous findings indicate that during oxidative stress conditions excess cholesterol autoxidizes to oxysterols. To date, the role of oxysterols and their potential interaction with fatty acids accumulation in NASH pathogenesis remains little investigated. We used the nutritional model of high fatty acids (HFA), high cholesterol (HCh) or high fat and high cholesterol (HFA+FCh) diets and explored by a lipidomic approach, the blood and liver distribution of fatty acids and oxysterols in response to dietary manipulation. We observed that HFA or HCh diets induced fatty liver without inflammation, which was otherwise observed only after supplementation of HFA+HCh. Very interestingly, the combination model was associated with a specific oxysterol fingerprint. The present work provides a complete analysis of the change in lipids and oxysterols profile induced by different lipid dietary model and their association with histological alteration of the liver. This study allows the generation of interesting hypotheses on the role of interaction of lipid and cholesterol metabolites in the liver injury during NAFLD development and progression. Moreover, the changes in the concentration and quality of oxysterols induced by a combination diet suggest a novel potential pathogenic mechanism in the progression from simple steatosis to steatohepatitis.
authors.affiliation: CURE University Centre for Liver Disease Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy. Electronic address: gaetano.serviddio@unifg.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Serviddio
authors.affiliation: CURE University Centre for Liver Disease Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bellanti
authors.affiliation: CURE University Centre for Liver Disease Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Villani
authors.affiliation: CURE University Centre for Liver Disease Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Tamborra
authors.affiliation: Laboratory of Vascular Biology and Mass Spectrometry, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Zerbinati
authors.affiliation: CURE University Centre for Liver Disease Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Blonda
authors.affiliation: Laboratory of Vascular Biology and Mass Spectrometry, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ciacciarelli
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino at San Luigi Gonzaga Hospital, 10043 Torino, Orbassano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Poli
authors.affiliation: CURE University Centre for Liver Disease Research and Treatment, Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Vendemiale
authors.affiliation: Laboratory of Vascular Biology and Mass Spectrometry, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Iuliano
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D004032:Diet; D059305:Diet, High-Fat; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000072376:Oxysterols / Q000378:metabolism; D051381:Rats
chemical_list: D005227:Fatty Acids; D000072376:Oxysterols; D002784:Cholesterol
keywords: Cholesterol excess; Fatty acids; Non-alcoholic fatty liver disease; Oxysterols