title: PPARα Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury.
abstract: Ischemia-reperfusion injury (IRI) remains a frequent complication in surgery, especially in case of steatotic livers that present decreased tolerance towards IRI. Apart from its major role in metabolism, activation of peroxisome proliferator-activated receptor α (PPARα) has been related with positive effects on IRI. In addition, the deacetylase enzyme sirtuin 1 (SIRT1) has recently emerged as a promising target for preventing IRI, through its interaction with stress-related mechanisms, such as endoplasmic reticulum stress (ERS). Taking this into account, this study aims to explore whether PPARα agonist WY-14643 could protect steatotic livers against IRI through sirtuins and ERS signaling pathway. Obese Zucker rats were pretreated or not pretreated with WY-14643 (10 mg/kg intravenously) and then submitted to partial (70%) hepatic ischemia (1 hour) followed by 24 hours of reperfusion. Liver injury (ALT levels), lipid peroxidation (MDA), SIRT1 activity, and the protein expression of SIRT1 and SIRT3 and ERS parameters (IRE1α, peIF2, caspase 12, and CHOP) were evaluated. Treatment with WY-14643 reduced liver injury in fatty livers, enhanced SIRT1 activity, and prevented ERS. Together, our results indicated that PPARα agonist WY-14643 may exert its protective effect in fatty livers, at least in part, via SIRT1 induction and ERS prevention.
authors.affiliation: Department of Experimental Pathology, Institute of Biomedical Research of Barcelona (IIBB-CSIC), IDIBAPS, Barcelona, 08036 Catalonia, Spain.
authors.forename: Eirini
authors.initials: E
authors.lastname: Pantazi
authors.affiliation: Department of Experimental Pathology, Institute of Biomedical Research of Barcelona (IIBB-CSIC), IDIBAPS, Barcelona, 08036 Catalonia, Spain.
authors.forename: Emma
authors.initials: E
authors.lastname: Folch-Puy
authors.affiliation: Department of Experimental Pathology, Institute of Biomedical Research of Barcelona (IIBB-CSIC), IDIBAPS, Barcelona, 08036 Catalonia, Spain.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bejaoui
authors.affiliation: Department of Experimental Pathology, Institute of Biomedical Research of Barcelona (IIBB-CSIC), IDIBAPS, Barcelona, 08036 Catalonia, Spain.
authors.forename: Arnau
authors.initials: A
authors.lastname: Panisello
authors.affiliation: Department of Life Sciences and Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Ana Teresa
authors.initials: AT
authors.lastname: Varela
authors.affiliation: Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Anabela Pinto
authors.initials: AP
authors.lastname: Rolo
authors.affiliation: Department of Life Sciences and Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Carlos Marques
authors.initials: CM
authors.lastname: Palmeira
authors.affiliation: Department of Experimental Pathology, Institute of Biomedical Research of Barcelona (IIBB-CSIC), IDIBAPS, Barcelona, 08036 Catalonia, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, 08036 Catalonia, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Roselló-Catafau
mesh_terms: D000818:Animals; D008099:Liver / Q000293:injuries*; D047493:PPAR alpha / Q000037:antagonists & inhibitors*; D051381:Rats; D011924:Rats, Zucker; D015427:Reperfusion Injury / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D047493:PPAR alpha; D056564:Sirtuin 1