SIRT1 activation by Taurine: in vitro evaluation, molecular docking and molecular dynamics simulation studies

Sirtuin1 (SIRT1) plays a major role in regulating different genes involved in several metabolic pathways. SIRT1 activators have protective role in several metabolic disorders. Taurine, a sulfur containing amino acid is involved in many physiological functions and has been reported as a beneficial molecule for regulating metabolic disorders. This study aims to investigate the effect of taurine on SIRT1 activation and its underlying mechanism. HepG2 cells were treated with different concentrations of Taurine. Subsequently, the cellular mRNA and protein expression and enzyme activity of SIRT1 were analyzed using quantitative real time and reverse transcriptase PCR, western blot and fluorescent assays. The effect of Taurine on key genes involved in lipid metabolism viz. PPAR-α, LXR-β, SREBP-1c and PGC-1α were analyzed using mRNA and protein expression data. The results showed a significant increase in SIRT1 protein expression and its activity levels (P<.05) in the cells treated with Taurine. PPAR-α, LXR-β, PGC-1α mRNA and protein levels were increased and SREBP-1c expression was decreased after treatment. Molecular docking and molecular dynamic simulation studies were carried out to understand the binding of taurine to SIRT1 protein with resveratrol as reference molecule. Molecular docking and simulation studies endorse the role of taurine in SIRT1 activation.  In conclusion, our data collectively establishes Taurine as a positive regulator of SIRT1.  The lipid lowering effect of Taurine via modulation of lipid metabolic genes may contribute to protection against metabolic disorders like obesity and age-related disease in humans.