SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance
Elisa Martino,
Anna Balestrieri,
Camilla Anastasio,
Martina Maione,
Luigi Mele,
Domenico Cautela,
Giuseppe Campanile,
Maria Luisa Balestrieri,
Nunzia D’Onofrio
Affiliations
Elisa Martino
Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy
Anna Balestrieri
Food Safety Department, Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute, 2, 80055 Portici, Italy
Camilla Anastasio
Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy
Martina Maione
Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy
Luigi Mele
Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Via Luciano Armanni 5, 80138 Naples, Italy
Domenico Cautela
Stazione Sperimentale per le Industrie delle Essenze e dei Derivati dagli Agrumi (SSEA)—Azienda Speciale CCIAA di Reggio Calabria, 89125 Reggio Calabria, Italy
Giuseppe Campanile
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy
Maria Luisa Balestrieri
Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy
Nunzia D’Onofrio
Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy
Emerging evidence indicates that defects in sirtuin signaling contribute to impaired glucose and lipid metabolism, resulting in insulin resistance (IR) and endothelial dysfunction. Here, we examined the effects of palmitic acid (PA) treatment on mitochondrial sirtuins (SIRT2, SIRT3, SIRT4, and SIRT5) and oxidative homeostasis in human endothelial cells (TeloHAEC). Results showed that treatment for 48 h with PA (0.5 mM) impaired cell viability, induced loss of insulin signaling, imbalanced the oxidative status (p p +) suppressed the PA-induced autophagy (mimic NC+PA) (p p < 0.01) mediated by the NLRP3/caspase-1 axis. Moreover, the unbalanced endothelial redox state induced by PA was counteracted by the antioxidant δ-valerobetaine (δVB), which was able to upregulate protein and mRNA expression of sirtuins, reduce reactive oxygen species (ROS) accumulation, and decrease cell death. Overall, results support the central role of SIRT3 in maintaining the endothelial redox homeostasis under IR and unveil the potential of the antioxidant δVB in enhancing the defense against IR-related injuries.
