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O‐GlcNAc signaling orchestrates metabolic adaptation to prolonged fasting
Author(s) -
Li Mindian,
Liu Jiayu,
Sehgal Raghav,
Wu Jing,
Zhang Pei,
Han Weiping,
Jha Abhishek,
Yang Xiaoyong
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.488.9
Subject(s) - catabolism , gluconeogenesis , metabolic pathway , purine metabolism , purine , metabolism , pentose phosphate pathway , biochemistry , citric acid cycle , biology , beta oxidation , urea cycle , endocrinology , medicine , glycolysis , amino acid , arginine , enzyme
Prolonged fasting reprograms metabolic pathways to foster stress resistance. O‐ linked b‐D‐ N‐ acetylglucosamine ( O‐ GlcNAc) glycosylation is essential in metabolic regulation and stress resistance. It is unknown whether and how O‐GlcNAc signaling catalyzed by O‐GlcNAc transferase (OGT) reprograms metabolic pathways during prolonged fasting. Here we report that OGT coordinates purine, lipid, amino acid and carbohydrate metabolism during prolonged fasting. Unbiased metabolomic profiling of mouse livers after 48‐hour fasting reveals that hepatic ablation of OGT impedes fasting‐associated changes in purine metabolism, phospholipid degradation and fatty acid oxidation. Loss of OGT also impedes amino acid catabolism through reduced flux through the urea cycle and reduced aspartate‐argininosuccinate shunt. Notably, the citric acid cycle is also inhibited in part through inhibition of succinate dehydrogenase activity, which is consistent with decreased oxygen consumption and energy production. These catabolic defects are correlated with reduced gluconeogenesis. Together, these results define OGT as a master regulator of metabolic adaptation during prolonged fasting in liver. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .