{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["2014"],"submitter":["Al Sharif M"],"pubmed_abstract":["Comprehensive understanding of the precise mode of action/adverse outcome pathway (MoA/AOP) of chemicals becomes a key step towards superseding the current repeated dose toxicity testing methodology with new generation predictive toxicology tools. The description and characterization of the toxicological MoA leading to non-alcoholic fatty liver disease (NAFLD) are of specific interest, due to its increasing incidence in the modern society. Growing evidence stresses on the PPAR γ ligand-dependent dysregulation as a key molecular initiating event (MIE) for this adverse effect. The aim of this work was to analyze and systematize the numerous scientific data about the steatogenic role of PPAR γ . Over 300 papers were ranked according to preliminary defined criteria and used as reliable and significant sources of data about the PPAR γ -dependent prosteatotic MoA. A detailed analysis was performed regarding proteins which PPAR γ -mediated expression changes had been confirmed to be prosteatotic by most experimental evidence. Two probable toxicological MoAs from PPAR γ ligand binding to NAFLD were described according to the Organisation for Economic Cooperation and Development (OECD) concepts: (i) PPAR γ activation in hepatocytes and (ii) PPAR γ inhibition in adipocytes. The possible events at different levels of biological organization starting from the MIE to the organ response and the connections between them were described in details."],"journal":["PPAR research"],"pagination":["432647"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3977565"],"repository":["biostudies-literature"],"pubmed_title":["Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPAR γ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease."],"pmcid":["PMC3977565"],"pubmed_authors":["Pajeva I","Alov P","Al Sharif M","Tsakovska I","Vitcheva V"],"additional_accession":[]},"is_claimable":false,"name":"Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPAR γ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease.","description":"Comprehensive understanding of the precise mode of action/adverse outcome pathway (MoA/AOP) of chemicals becomes a key step towards superseding the current repeated dose toxicity testing methodology with new generation predictive toxicology tools. The description and characterization of the toxicological MoA leading to non-alcoholic fatty liver disease (NAFLD) are of specific interest, due to its increasing incidence in the modern society. Growing evidence stresses on the PPAR γ ligand-dependent dysregulation as a key molecular initiating event (MIE) for this adverse effect. The aim of this work was to analyze and systematize the numerous scientific data about the steatogenic role of PPAR γ . Over 300 papers were ranked according to preliminary defined criteria and used as reliable and significant sources of data about the PPAR γ -dependent prosteatotic MoA. A detailed analysis was performed regarding proteins which PPAR γ -mediated expression changes had been confirmed to be prosteatotic by most experimental evidence. Two probable toxicological MoAs from PPAR γ ligand binding to NAFLD were described according to the Organisation for Economic Cooperation and Development (OECD) concepts: (i) PPAR γ activation in hepatocytes and (ii) PPAR γ inhibition in adipocytes. The possible events at different levels of biological organization starting from the MIE to the organ response and the connections between them were described in details.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014","modification":"2024-11-21T09:55:00.447Z","creation":"2019-03-27T01:24:31Z"},"accession":"S-EPMC3977565","cross_references":{"pubmed":["24772164"],"doi":["10.1155/2014/432647"]}}