Hexosamine biosynthetic pathway and O-GlcNAc-processing enzymes regulate daily rhythms in protein O-GlcNAcylation

Xianhui Liu, Ivana Blaženović, Adam J. Contreras, Thu M. Pham, Christine A. Tabuloc, Ying H. Li, Jian Ji, Oliver Fiehn and Joanna C. Chiu ()
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Xianhui Liu: College of Agricultural and Environmental Sciences, University of California
Ivana Blaženović: West Coast Metabolomics Center, University of California
Adam J. Contreras: College of Agricultural and Environmental Sciences, University of California
Thu M. Pham: College of Agricultural and Environmental Sciences, University of California
Christine A. Tabuloc: College of Agricultural and Environmental Sciences, University of California
Ying H. Li: College of Agricultural and Environmental Sciences, University of California
Jian Ji: School of Food Science, State Key Laboratory of Food Science and Technology, National Engineering Research Center for Functional Foods, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University
Oliver Fiehn: West Coast Metabolomics Center, University of California
Joanna C. Chiu: College of Agricultural and Environmental Sciences, University of California

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract The integration of circadian and metabolic signals is essential for maintaining robust circadian rhythms and ensuring efficient metabolism and energy use. Using Drosophila as an animal model, we show that cellular protein O-GlcNAcylation exhibits robust 24-hour rhythm and represents a key post-translational mechanism that regulates circadian physiology. We observe strong correlation between protein O-GlcNAcylation rhythms and clock-controlled feeding-fasting cycles, suggesting that O-GlcNAcylation rhythms are primarily driven by nutrient input. Interestingly, daily O-GlcNAcylation rhythms are severely dampened when we subject flies to time-restricted feeding at unnatural feeding time. This suggests the presence of clock-regulated buffering mechanisms that prevent excessive O-GlcNAcylation at non-optimal times of the day-night cycle. We show that this buffering mechanism is mediated by the expression and activity of GFAT, OGT, and OGA, which are regulated through integration of circadian and metabolic signals. Finally, we generate a mathematical model to describe the key factors that regulate daily O-GlcNAcylation rhythm.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24301-7

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DOI: 10.1038/s41467-021-24301-7

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