Proteino-Glcnacylation Levels Are Regulated Independently Of Dietary Intake In A Tissue And Time-Specific Manner During Rat Postnatal Development

Aim Metabolic sources switch from carbohydratesin utero, to fatty acids after birth and then a mix once adults.O-GlcNAcylation (O-GlcNAc) is a post-translational modification considered as a nutrient sensor. The purpose of this work was to assess changes in proteinO-GlcNAc levels, regulatory enzymes and metabolites during the first periods of life and decipher the impact ofO-GlcNAcylation on cardiac proteins. Methods Heart, brain and liver were harvested from rats before and after birth (D-1 and D0), in suckling animals (D12), after weaning with a standard (D28) or a low-carbohydrate diet (D28F), and adults (D84).O-GlcNAc levels and regulatory enzymes were evaluated by western blots. Mass spectrometry (MS) approaches were performed to quantify levels of metabolites regulatingO-GlcNAc and identify putative cardiacO-GlcNAcylated proteins. Results ProteinO-GlcNAc levels decrease drastically and progressively from D-1 to D84 (13-fold,P < .05) in the heart, whereas the changes were opposite in liver and brain.O-GlcNAc levels were unaffected by weaning diet in any tissues. Changes in expression of enzymes and levels of metabolites regulatingO-GlcNAc were tissue-dependent. MS analyses identified changes in putative cardiacO-GlcNAcylated proteins, namely those involved in the stress response and energy metabolism, such as ACAT1, which is onlyO-GlcNAcylated at D0. Conclusion Our results demonstrate that proteinO-GlcNAc levels are not linked to dietary intake and regulated in a time and tissue-specific manner during postnatal development. We have identified by untargeted MS putative proteins with a particularO-GlcNAc signature across the development process suggesting specific role of these proteins.