To investigate the impact of ketogenesis, we subjected 3-month-old mice with either a ketogenic diet (KD) or a control diet (Ctrl) group for 9 weeks. Similar to previous studies, KD led to a significantly decreased mice weight (Fig. 1b). Furthermore, adherence to a KD dramatically elevated blood β-OHB <<28877458/28877456>> and decreased blood glucose <33838492> (Fig. 1c, d). To investigate how KD affected mice liver proteomes post-translationally, we probed the liver tissues with various pan-PTM antibodies. KD dramatically increased the global levels of Kbhb, acetylation (Kac), and O-GlcNAcylation, with the level of Kbhb increased most (6 fold relative to control). On the other hand, KD led to the decreased levels of lactylation and succinylation, but did not alter the levels of phosphorylation, ubiquitination and sumoylation.For label-free proteomic and β-hydroxybutyrylomic quantifications, 6 liver samples of Ctrl or KD mice were pooled into two samples, and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). For metabolomic profilling, 6 liver samples from Ctrl or KD mice were also adopted for untargeted metabolomic profiling in Ctrl and KD mice, respectively.