Emerging Role of Sirtuin 2 in the Regulation of Mammalian Metabolism. (November 2015)

• Record Type: Journal Article
• Authors: Gomes, Pedro; Fleming Outeiro, Tiago; Cavadas, Cláudia
• Is Part Of: Trends in pharmacological sciences. Volume 36:Number 11(2015)
• Page Start: 756
• Page End: 768
• Publication Date: 2015-11
• Subjects: Pharmacology -- Periodicals; Pharmacology -- trends -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Electronic journals; Periodicals; 615.1
• DOI: 10.1016/j.tips.2015.08.001
• Languages: English
• ISSNs: 0165-6147

Abstract

Abstract : Sirtuins are an evolutionarily conserved family of NAD + -dependent deacylases that display diversity in subcellular localization and function. SIRT2, the predominantly cytosolic sirtuin, is among the least understood of the seven mammalian sirtuin isoforms described (SIRT1–7). The purpose of this review is to summarize the most recent findings about the potential roles and effects of SIRT2 in mammalian metabolic homeostasis. We discuss the different functions and targets of SIRT2 in various physiological processes, including adipogenesis, fatty acid oxidation, gluconeogenesis, and insulin sensitivity. We also cover the role of SIRT2 in inflammation and oxidative stress due to the possible implications for metabolic disorders. Finally, we consider its potential as a therapeutic target for the prevention and treatment of type 2 diabetes. Trends: Several SIRT2 deacetylation targets play important roles in metabolic homeostasis. SIRT2 inhibits adipogenesis by deacetylating FOXO1 and thus may protect against insulin resistance. SIRT2 sensitizes cells to the action of insulin by physically interacting with and activating Akt and downstream targets. SIRT2 mediates mitochondrial biogenesis by deacetylating PGC-1α, upregulates antioxidant enzyme expression by deacetylating FOXO3a, and thereby reduces ROS levels. SIRT2 suppresses inflammatory responses in mice through p65 deacetylation and inhibition of NF-κB activity.