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The purpose of this work was to assess changes in protein <jats:italic>O<\/jats:italic>\u2010GlcNAc levels, regulatory enzymes and metabolites during the first periods of life and decipher the impact of <jats:italic>O<\/jats:italic>\u2010GlcNAcylation on cardiac proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Heart, brain and liver were harvested from rats before and after birth (D\u20101 and D0), in suckling animals (D12), after weaning with a standard (D28) or a low\u2010carbohydrate diet (D28F), and adults (D84). <jats:italic>O<\/jats:italic>\u2010GlcNAc levels and regulatory enzymes were evaluated by western blots. Mass spectrometry (MS) approaches were performed to quantify levels of metabolites regulating <jats:italic>O<\/jats:italic>\u2010GlcNAc and identify putative cardiac <jats:italic>O<\/jats:italic>\u2010GlcNAcylated proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Protein <jats:italic>O<\/jats:italic>\u2010GlcNAc levels decrease drastically and progressively from D\u20101 to D84 (13\u2010fold, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05) in the heart, whereas the changes were opposite in liver and brain. <jats:italic>O<\/jats:italic>\u2010GlcNAc levels were unaffected by weaning diet in any tissues. Changes in expression of enzymes and levels of metabolites regulating <jats:italic>O<\/jats:italic>\u2010GlcNAc were tissue\u2010dependent. MS analyses identified changes in putative cardiac <jats:italic>O<\/jats:italic>\u2010GlcNAcylated proteins, namely those involved in the stress response and energy metabolism, such as ACAT1, which is only <jats:italic>O<\/jats:italic>\u2010GlcNAcylated at D0.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that protein <jats:italic>O<\/jats:italic>\u2010GlcNAc levels are not linked to dietary intake and regulated in a time and tissue\u2010specific manner during postnatal development. We have identified by untargeted MS putative proteins with a particular <jats:italic>O<\/jats:italic>\u2010GlcNAc signature across the development process suggesting specific role of these proteins.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13566","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T22:09:28Z","timestamp":1602022168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Protein <i>O<\/i>\u2010GlcNAcylation levels are regulated independently of dietary intake in a tissue and time\u2010specific manner during rat postnatal development"],"prefix":"10.1111","volume":"231","author":[{"given":"Thomas","family":"Dupas","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Nantes CHU Nantes CNRS INSERM, l\u2019institut du thorax Nantes 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