Inhibition of PGC-1α activity by Sirt6 occurs via deacetylation of GCN5, increasing its acetyltransferase activity, which is a form of histone acetylation and thereby increases the acetylation of PGC-1α which leads to inhibition of hepatic gluconeogenesis and thereby hyperglycemia (Figure 3: Schematic representation of molecular mechanism of Sirt6 in various diseases) (Jeninga et al., 2010; Satoh and Imai, 2014; Sharabi et al., 2017; Kanwal and Dsouza, 2019; Singh et al., 2019). Here, PPARGC1A is linked to Hyperglycemia.