Y, preventing fatty acid-induced cell damage. Regardless of the information obtained, AntiOxCIN4 effects on cellular and mitochondrial energy metabolism in vivo weren’t studied. Inside the present work, we proposed that AntiOxCIN4 (2.five mg/day/animal) may possibly avoid non-alcoholic fatty liver (NAFL) phenotype development within a C57BL/6J mice fed with 30 high-fat, 30 high-sucrose diet for 16 weeks. HepG2 cells treated with AntiOxCIN4 (100 M, 48 h) ahead of the exposure to supraphysiologic free of charge fatty acids (FFAs) (250 M, 24 h) have been utilised for complementary research. AntiOxCIN4 decreased body (by 43 ), liver weight (by 39 ), and plasma hepatocyte damage markers in WD-fed mice. Hepatic-related parameters related having a reduction of fat liver accumulation (by 600 ) as well as the remodeling of fatty acyl chain composition compared together with the WD-fed group had been improved. Data from human HepG2 cells confirmed that a reduction of lipid droplets size and quantity might be a result from AntiOxCIN4-induced stimulation of fatty acid oxidation and mitochondrial OXPHOS remodeling. In WD-fed mice, AntiOxCIN4 also induced a hepatic metabolism remodeling by upregulating mitochondrial OXPHOS, anti-oxidant defense system and phospholipid membrane composition, which can be mediated by the PGC-1-SIRT3 axis. AntiOxCIN4 prevented lipid accumulation-driven autophagic flux impairment, by growing lysosomal proteolytic capacity. Corresponding author. CNC – Center for Neuroscience and Cell Biology, CIBB Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal. Corresponding author. Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland. Corresponding author. CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal.SDF-1 alpha/CXCL12 Protein Purity & Documentation E-mail addresses: fborges@fc.CA125 Protein medchemexpress up.PMID:23557924 pt (F. Borges), [email protected] (M.R. Wieckowski), [email protected] (P.J. Oliveira). 1 These authors contributed equally. 2 These authors share senior authorship. doi.org/10.1016/j.redox.2022.102400 Received 27 April 2022; Received in revised kind five July 2022; Accepted six July 2022 Offered on the internet 16 July 2022 2213-2317/2022 Published by Elsevier B.V. This really is an open access report under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).R. Amorim et al.Redox Biology 55 (2022)AntiOxCIN4 enhanced NAFL phenotype of WD-fed mice, through 3 major mechanisms: a) increase mitochondrial function (fatty acid oxidation); b) stimulation antioxidant defense program (enzymatic and non-enzymatic) and; c) stop the impairment in autophagy. Together, the findings help the possible use of AntiOxCIN4 within the prevention/treatment of NAFLD.Abbreviations m mitochondrial transmembrane electric possible 4-HNE 4-hydroxy-2-nonenal AA antimycin-A ABTS two,two -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) AKT protein kinase B complex ALT alanine aminotransferase AMPK AMP-activated protein kinase AST aspartate aminotransferase BCA bicinchoninic acid BSA bovine serum albumin CAT catalase CE cholesteryl esters Chol absolutely free cholesterol DAG diacylglycerols DNL de novo lipogenesis DNP dinitrophenol DTNB 5,five -dithio-bis-(2-nitrobenzoic acid) DTT dithiothreitol ER endoplasmic reticulum FAs fatty acids FAO fatty acid oxidation FCCP carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone FFAs free fatty acids G6PC glucose-6-phosphatase GAPDH glyceraldehyde 3-phosphate dehydrogenase GR glutathione reductase GSH glutathione H E hematoxylin e.