Pharmacological activation of PPARβ/δ preserves mitochondrial respiratory function in ischemia/reperfusion via stimulation of fatty acid oxidation-linked respiration and PGC-1α/NRF-1 signaling

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dc.contributor.authorPapatheodorou, Ioanna
dc.contributor.authorMakrecka-Kuka, Marina
dc.contributor.authorKuka, Janis
dc.contributor.authorLiepinsh, Edgars
dc.contributor.authorDambrova, Maija
dc.contributor.authorLazou, Antigone
dc.contributor.institutionFaculty of Pharmacy
dc.date.accessioned2022-10-26T10:10:01Z
dc.date.available2022-10-26T10:10:01Z
dc.date.issued2022-08-15
dc.descriptionFunding Information: The work was supported by core institutional funds and the Graduate Program “Applications of Biology” of the School of Biology, Aristotle University of Thessaloniki. Funding Information: The authors thank Dr Reinis Vilskersts for his assistance during ex vivo experimental procedures and Stanislava Korzh for her assistance during high resolution fluorespirometry procedures. This article is based upon work from COST Action EU-CARDIOPROTECTION CA16225 supported by COST (European Cooperation in Science and Technology). Publisher Copyright: Copyright © 2022 Papatheodorou, Makrecka-Kuka, Kuka, Liepinsh, Dambrova and Lazou.
dc.description.abstractMyocardial ischemia/reperfusion (I/R) injury leads to significant impairment of cardiac function and remains the leading cause of morbidity and mortality worldwide. Activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) confers cardioprotection via pleiotropic effects including antioxidant and anti-inflammatory actions; however, the underlying mechanisms are not yet fully elucidated. The aim of this study was to investigate the effect of PPARβ/δ activation on myocardial mitochondrial respiratory function and link this effect with cardioprotection after ischemia/reperfusion (I/R). For this purpose, rats were treated with the PPARβ/δ agonist GW0742 and/or antagonist GSK0660 in vivo. Mitochondrial respiration and ROS production rates were determined using high-resolution fluororespirometry. Activation of PPARβ/δ did not alter mitochondrial respiratory function in the healthy heart, however, inhibition of PPARβ/δ reduced fatty acid oxidation (FAO) and complex II-linked mitochondrial respiration and shifted the substrate dependence away from succinate-related energy production and towards NADH. Activation of PPARβ/δ reduced mitochondrial stress during in vitro anoxia/reoxygenation. Furthermore, it preserved FAO-dependent mitochondrial respiration and lowered ROS production at oxidative phosphorylation (OXPHOS)-dependent state during ex vivo I/R. PPARβ/δ activation was also followed by increased mRNA expression of components of FAO -linked respiration and of transcription factors governing mitochondrial homeostasis (carnitine palmitoyl transferase 1b and 2-CPT-1b and CPT-2, electron transfer flavoprotein dehydrogenase -ETFDH, peroxisome proliferator-activated receptor gamma co-activator 1 alpha- PGC-1α and nuclear respiratory factor 1-NRF-1). In conclusion, activation of PPARβ/δ stimulated both FAO-linked respiration and PGC-1α/NRF -1 signaling and preserved mitochondrial respiratory function during I/R. These effects are associated with reduced infarct size.en
dc.description.statusPeer reviewed
dc.format.extent6434724
dc.identifier.citationPapatheodorou, I, Makrecka-Kuka, M, Kuka, J, Liepinsh, E, Dambrova, M & Lazou, A 2022, 'Pharmacological activation of PPARβ/δ preserves mitochondrial respiratory function in ischemia/reperfusion via stimulation of fatty acid oxidation-linked respiration and PGC-1α/NRF-1 signaling', Frontiers in Endocrinology, vol. 13, 941822. https://doi.org/10.3389/fendo.2022.941822
dc.identifier.doi10.3389/fendo.2022.941822
dc.identifier.issn1664-2392
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/9675
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85136862089&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofFrontiers in Endocrinology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectcardioprotection
dc.subjectelectron transport system
dc.subjectfatty acid oxidation
dc.subjectischemia/reperfusion
dc.subjectmitochondrial respiration
dc.subjectPPARβ/δ
dc.subjectROS
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectEndocrinology, Diabetes and Metabolism
dc.subjectSDG 3 - Good Health and Well-being
dc.titlePharmacological activation of PPARβ/δ preserves mitochondrial respiratory function in ischemia/reperfusion via stimulation of fatty acid oxidation-linked respiration and PGC-1α/NRF-1 signalingen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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