Changes in transcriptomic landscape with macronutrients intake switch are independent from O-GlcNAcylation levels in heart throughout postnatal development in rats.

ABSTRACT

Background: Dietary intake and metabolism variations are associated with molecular changes and more particularly in the transcriptome. O-GlcNAcylation is a post-translational modification added and removed respectively by OGT and OGA. The UDP-GlcNAc, the substrate of OGT, is produced by UAP1 and UAP1L1. O-GlcNAcylation is qualified as a metabolic sensor and is involved in the modulation of gene expression. We wanted to unveil if O-GlcNAcylation is linking metabolic transition to transcriptomic changes and to highlight modifications of O-GlcNAcylation during the postnatal cardiac development. Methods: Hearts were harvested from rats at birth (D0), before (D12) and after suckling to weaning transition with normal (D28) or delayed weaning diet from D12 to D28 (D28F). O-GlcNAcylation levels and proteins expression were evaluated by Western blot. Cardiac transcriptomes were evaluated via 3'SRP analysis. Results: Cardiac O-GlcNAcylation levels and nucleocytoplasmic OGT (ncOGT) were decreased at D28 while full length OGA (OGA) was increased. O-GlcNAcylation levels did not changed with delayed weaning diet while ncOGT and OGA were respectively increased and decreased. Uapl1 was the only O-GlcNAcylation-related gene identified as differentially expressed throughout postnatal development. Conclusion: Macronutrients switch promotes changes in the transcriptome landscape that are independent from O-GlcNAcylation levels. UAP1 and UAP1L1 are not the main regulator element of O-GlcNAcylation throughout postnatal development.