Sirtuins Link Inflammation and Metabolism

Abstract

Sirtuins (SIRT), first discovered in yeast as NAD+ dependent epigenetic and metabolic regulators, have comparable activities in human physiology and disease. Mounting evidence supports that the seven-member mammalian sirtuin family (SIRT1–7) guard homeostasis by sensing bioenergy needs and responding by making alterations in the cell nutrients. Sirtuins play a critical role in restoring homeostasis during stress responses. Inflammation is designed to “defend and mend” against the invading organisms. Emerging evidence supports that metabolism and bioenergy reprogramming direct the sequential course of inflammation; failure of homeostasis retrieval results in many chronic and acute inflammatory diseases. Anabolic glycolysis quickly induced (compared to oxidative phosphorylation) for ROS and ATP generation is needed for immune activation to “defend” against invading microorganisms. Lipolysis/fatty acid oxidation, essential for cellular protection/hibernation and cell survival in order to “mend,” leads to immune repression. Acute/chronic inflammations are linked to altered glycolysis and fatty acid oxidation, at least in part, by NAD+ dependent function of sirtuins. Therapeutically targeting sirtuins may provide a new class of inflammation and immune regulators. This review discusses how sirtuins integrate metabolism, bioenergetics, and immunity during inflammation and how sirtuin-directed treatment improves outcome in chronic inflammatory diseases and in the extreme stress response of sepsis.

MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-κB and AKT Pathways

“…SIRT1 shows strong anti-inflammation activity [38]. In sepsis, SIRT1 may promote the termination of the NF-κB-dependent transcription by its deacetylation effect of p65 and thus play a role in sepsis protection [6,39]. Additionally, SIRT1 directly or indirectly regulates the AKT pathway, [40,41].…”

Reduced expression of SIRT1 and SOD-1 and the correlation between these levels in various regions of the brains of patients with Alzheimer's disease

“…Interestingly, silent information regulators (SIRTs) (sirtuin or silent mating-type information regulator 2 (Sir2) proteins) are evolutionarily conserved NAD + -dependent deacetylases that have beneficial effects in connexion with age-related disorders,10 as well as being involved in resistance to stress and metabolic regulation 11. Their important role in the detoxification of ROS generated by hypoxia and certain cytotoxic drugs has been reported 12.…”

Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and <em>in Vitro </em>Testing

“…Sirtuins are nicotinamide adenine dinucleotide (NAD + )-dependent class III histone deacetylases that have been linked to the pathogenesis of numerous diseases such as HIV, metabolic disorders, neurodegeneration (including Alzheimer's disease and Parkinson's disease) and cancer [21][22][23][24][25][26][27][28]. Since the p-ANAPL library consists of compounds with a broad range of already reported activities, e.g.…”