Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

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

Authors: Liu, Xianhui; Blaženović, Ivana; Contreras, Adam J; Pham, Thu M; Tabuloc, Christine A; Li, Ying H; Ji, Jian; Fiehn, Oliver; Chiu, Joanna C

Published In Nat Commun, (2021 Jul 07)

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.

PubMed ID: 34234137 Exiting the NIEHS site

MeSH Terms: Acetylglucosamine/metabolism; Animals; Animals, Genetically Modified; Biosynthetic Pathways/genetics; Circadian Clocks/genetics; Circadian Rhythm/genetics*; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster; Feeding Behavior/physiology; Female; Gene Expression Profiling; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/genetics; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/metabolism*; Hexosamines/biosynthesis*; Male; Models, Animal; N-Acetylglucosaminyltransferases/genetics; N-Acetylglucosaminyltransferases/metabolism*; Period Circadian Proteins/genetics; Period Circadian Proteins/metabolism; Protein Processing, Post-Translational/physiology*

Back
to Top