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Sepsis in the young population, which is particularly at risk, is rarely studied. O -GlcNAcylation is a post-translational modification involved in cell survival, stress response and metabolic regulation. O -GlcNAc stimulation is beneficial in adult septic rats. This modification is physiologically higher in the young rat, potentially limiting the therapeutic potential of O -GlcNAc stimulation in young septic rats. The aim is to evaluate whether O -GlcNAc stimulation can improve sepsis outcome in young rats. Endotoxemic challenge was induced in 28-day-old rats by lipopolysaccharide injection ( E. Coli O111:B4, 20 mg·kg -1 ) and compared to control rats (NaCl 0.9%). One hour after lipopolysaccharide injection, rats were randomly assigned to no therapy, fluidotherapy (NaCl 0.9%, 10 mL·kg -1 ) ± NButGT (10 mg·kg -1 ) to increase O -GlcNAcylation levels. Physiological parameters and plasmatic markers were evaluated 2h later. Finally, untargeted mass spectrometry was performed to map cardiac O -GlcNAcylated proteins. Lipopolysaccharide injection induced shock with a decrease in mean arterial pressure and alteration of biological parameters ( p &lt; 0.05). NButGT, contrary to fluidotherapy, was associated with an improvement of arterial pressure ( p &lt; 0.05). ATP citrate lyase was identified among the O -GlcNAcylated proteins. In conclusion, O -GlcNAc stimulation improves outcomes in young septic rats. Interestingly, identified O -GlcNAcylated proteins are mainly involved in cellular metabolism.

An O-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat