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Title: PPARα Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury
Authors: Pantazi, Eirini
Folch-Puy, Emma
Bejaoui, Mohamed
Panisello, Arnau 
Varela, Ana Teresa 
Rolo, Anabela Pinto 
Palmeira, Carlos M. 
Roselló-Catafau, Joan 
Issue Date: 2015
Publisher: Hindawi
Project: fellowship from AGAUR (2012FI B00382), Generalitat de Catalunya, Barcelona, Catalonia, Spain. 
Fondo de Investigaciones Sanitarias (FIS PI12/00519) 
Serial title, monograph or event: BioMed Research International
Volume: 2015
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.
ISSN: 2314-6133
DOI: 10.1155/2015/894679
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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