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

大鼠出生后发育过程中,转录组景观随宏量营养素摄入量变化的变化与心脏 O-GlcNAc 糖基化水平无关

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作者:Antoine Persello, Thomas Dupas, Amandine Vergnaud, Angélique Blangy-Letheule, Virginie Aillerie, Angélique Erraud, Yannick Guilloux, Manon Denis, Benjamin Lauzier

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.

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.

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.

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