O-GlcNAc levels are regulated in a tissue and time specific manner during post-natal development, independently of dietary intake

Background O-GlcNAcylation is a well-preserved, ubiquitous, post-translational modification involved in response to stress, considered as a nutrient sensor. GlcNAc moiety is added and removed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. Metabolic sources vary from carbohydrate in utero, to fatty acid after birth then a mix once adult. Purpose Study the evolution of O-GlcNAc levels during the first period of life and decipher the impact of O-GlcNAc on cardiac proteins. Methods Heart and brain were harvested from Wistar rats before and after birth (D-1 and D0), in suckling animals (D12), after weaning (D28) with a standard or a carbohydrate free diet, and when adults (D84). O-GlcNAc levels, GFAT, OGT and OGA protein expression were evaluated by western blot. Mass spectrometry approaches were performed to (i) quantify known regulator of O-GlcNAc and (ii) identify cardiac O-GlcNAcylated proteins at D0 and D28. Results Cardiac protein O-GlcNAc levels decrease progressively from D-1 to D84 (13 fold, P Conclusion We demonstrate for the first time that O-GlcNAc levels are not linked to the dietary sources. Our results suggest that glutamine and UDP-GlcNAc are not the main regulatory element of O-GlcNAc levels. Proteins identified by untargeted mass spectrometry will need to be specifically studied to better understand the impact of O-GlcNAcylation during development, growth or stress response.