In living organisms and individual cells, post-translational modifications (PTMs) of proteins are crucial for regulation diverse cellular functions, such as DNA replication, transcription, tissue differentiation, apoptosis, inflammation and so on (Berdasco and Esteller, 2010; Lee, 2013). To date, more than 500 discrete types of PTMs across all 20 protein amino acids have been identified (Keenan et al., 2021). In addition to extensive studies of common PTMs, like phosphorylation and acetylation (Acetyllysine, KAc) (Verdin and Ott, 2015), several novel protein acetylation, such as, Lysine malonylation (Malonyllysine, KMal) (Xie et al., 2012), Lysine succinylation (Succinyllysine, KSu) (Xie et al., 2012), Lysine lactylation (Lactyllysine, KLa) (Qin et al., 2019), Lysine propionylation (Propionyllysine, KPr) (Chen et al., 2007), Lysine butyrylation (Butyryllysine, KBu) (Chen et al., 2007), Lysine β-hydroxybutyrylation (β-hydroxybutyryllysine, KHb) (Xie et al., 2016), Lysine glutarylation (Glutaryllysine, KGl) (Tan et al., 2014) and Lysine crotonylation (Crotonyllysine, KCr) (Tan et al., 2011) have been discovered in recent years. Moreover, these acylations have been associated with cellular metabolism (Sabari et al., 2017). Among aforementioned lysine acylations, KCr is involved in the diverse physiopathologic processes of some diseases, such as, neuropsychiatric disorder, acute kidney injury, mouse spermatogenesis, Alzheimer’s disease (AD) and cancers (Liu et al., 2017; Sun et al., 2020; Wan et al., 2019; Wang et al., 2019b). Although Lysine crotonylome reveals many studies of histone crotonylation and non-histone crotonylation (Wu et al., 2017), however, whether the levels of protein KCr could be affected in HFD-induced diseases have not yet been fully addressed.
High-fat diet (HFD), known as the western diet, has been associated with neuroinflammation, apoptosis, necrosis and cognitive deficits in distinct brain regions (Keshk et al., 2020; Pistell et al., 2010). Recent studies indicates that protein acylation modifications associated with HFD and obesity in brain mainly focus on acetylation (Cai et al., 2020; Chen et al., 2015; Gonçalves et al., 2017). On the other hand, while many studies about lysine crotonylation have been reported since 2011, the influence of short-term HFD on protein KCr in cerebral cortex remains relatively under explored. In this study, our preliminary research shows that the total KCr levels of cerebral cortex among nine types of lysine acylations are significantly increased after 7 and 21 days HFD compared with chow diet. Meanwhile, current results highlight that KCr modification might become a potential intervention target to fight against HFD-related brain diseases.