Ketone ester alleviates sepsis-associated liver injury through β-hydroxybutyrylation of STAT1

This study tested whether lysine beta-hydroxybutyrylation (Kbhb) of STAT1 at K679 mediates the protection of ketone ester (KE) against LPS-induced liver injury, using STAT1 p.K679R knock-in mice and cell models. In wild-type mice, KE pretreatment alleviated liver histopathological injury, reduced serum ALT and AST, and decreased the Bax/Bcl-2 ratio, and these effects were significantly attenuated in K679R mice. KE also reduced hepatic M1 macrophage markers, IL-6 and IL-12 expression and STAT1 Ser727 phosphorylation in wild-type mice, and these effects were attenuated by K679R.