VPA reduced transcriptional activity of FoxO1 via acetylation. HepG2 cells were co-transfected with expression vectors for wild-type (wt) FoxO1, AA-mutant FoxO1, RR-mutant FoxO1, or QQ-mutant FoxO1, as well as luciferase vectors conjugated with G6P promoter (A) or PCK1 promoter (B). VPA administration decreased hyperglycemia-induced promoter activity in HepG2 cells transfected with wild-type FoxO1, but not mutant FoxO1. The graphs show the mean ± SEM of three independent experiments (** p < 0.01 vs. wt FoxO1 in 5.5 mmol/L glucose; #
p < 0.05, ##
p < 0.01 vs. wt FoxO1 in 30 mmol/L glucose); (C) VPA administration under hyperglycemic conditions resulted in increased FoxO1 acetylation in HepG2 cells transfected with wt FoxO1, but not mutant FoxO1.