The role of class I histone deacetylase (HDAC) on gluconeogenesis in liver

► A novel class I HDAC inhibitor decreased hepatic PEPCK mRNA and gluconeogenesis. ► Inhibition of HDAC decreased PEPCK by reducing HNF4α expression and FoxO1 activity. ► siRNA knockdown of HDAC1 in HepG2 cells reduced the expression of PEPCK and HNF4α. ► Inhibition of class I HDAC improves glucose homeostasis in HFD mice.