Emerging roles of Sirtuins in alleviating alcoholic liver Disease: A comprehensive review

Sirtuins (SIRTs), a NAD+ family of dependent deacetylases, are involved in the regulation of various human diseases. Recently, accumulating evidence has uncovered number of substrates and crucial roles of SIRTs in the pathogenesis of alcoholic liver disease (ALD). However, systematic reports are still lacking, so this review provides a comprehensive profile of the crucial physiological functions of SIRTs and its role in attenuating ALD, including alcoholic liver steatosis, steatohepatitis, and fibrosis. SIRTs play beneficial roles in energy/lipid metabolism, oxidative stress, inflammatory response, mitochondrial homeostasis, autophagy and necroptosis of ALD via regulating multiple signaling transduction pathways such as AMPK, LKB1, SREBP1, Lipin1, PGC-1α, PPARα/γ, FoxO1/3a, Nrf2/p62, mTOR, TFEB, RIPK1/3, HMGB1, NFATc4, NF-κB, TLR4, NLRP3, P2X7R, MAPK, TGF1β/Smads and Wnt/β-catenin. In addition, the mechanism and clinical application of natural/ synthetic SIRTs agonists in ALD are summarized, which provide a new idea for the treatment of ALD and basic foundation for further studies into target drugs.