O-GlcNAc stimulation is beneficial in sepsis in the young rat, involvement of the ATP-citrate lyase

Introduction The young population, particularly at risk of septic shock, is rarely studied. The O-GlcNAcylation is a post-translational modification involved in cell survival, metabolism and stress response. We have shown that O-GlcNAc stimulation at the early phase of septic shock is beneficial in adult rats. Considering that O-GlcNAc levels are higher in the young, the impact of O-GlcNAc stimulation on sepsis in the young should be tested. Objective Evaluate if O-GlcNAc stimulation could improve sepsis outcomes in young. Method Endotoxemic shock was induced in 28 days old rats by injection of LPS (O111 :B4, 20 mg.kg−1–LPS) and compared to control rats (injection of saline–CTRL). One hour after LPS injection rats were randomly assigned to no therapy (LPS), fluidotherapy (saline, 10 mL.kg−1–LPS + R) ± NButGT (10 mg.kg−1–NButGT) to increase O-GlcNAc levels (n = 11 per group). Physiological functions and plasmatic markers were evaluated 2 hours later. Impact of treatment was evaluated with an adapted Pediatric RISk of Mortality score (PRISM score) and mortality was evaluated over 36 hours (n = 16 per group). Untargeted mass spectrometry was performed to identify cardiac O-GlcNAcylated proteins. Results LPS induced a shock (mean arterial pressure (MAP): CTRL: 67.2 ± 1.9; LPS: 50.7 ± 2.1 mmHg; P  Conclusion O-GlcNAc stimulation acutely improves outcome in young septic shock rat. The impact of O-GlcNAcylation on ACLY is a potential issue to decipher the role of this protein during sepsis.