Molecular exploration of the diurnal alteration of glycogen structural fragility and stability in time-restricted-feeding mouse liver
Document Type
Journal Article
Publication Title
International Journal of Biological Macromolecules
Volume
277
Publisher
Elsevier
School
Centre for Precision Health / School of Medical and Health Sciences
Funders
National Natural Science Foundation of China / Research Foundation for Advanced Talents of Guandong Provincial People's Hospital / Hubei Provincial Natural Science Foundation
Grant Number
32171281, KY012023293, 2022CFB092
Abstract
The structure of glycogen α particles in healthy mouse liver has two states: stability and fragility. In contrast, glycogen α particles in diabetic liver present consistent fragility, which may exacerbate hyperglycemia. Currently, the molecular mechanism behind glycogen structural alteration is still unclear. In this study, we characterized the fine molecular structure of liver glycogen α particles in healthy mice under time-restricted feeding (TRF) mode during a 24-h cycle. Then, differentially expressed genes (DEGs) in the liver during daytime and nighttime were revealed via transcriptomics, which identified that the key downregulated DEGs were mainly related to insulin secretion in daytime. Furthermore, GO annotation and KEGG pathway enrichment found that negative regulation of the glycogen catabolic process and insulin secretion process were significantly downregulated in the daytime. Therefore, transcriptomic analyses indicated that the structural stability of glycogen α particles might be correlated with the glycogen degradation process via insulin secretion downregulation. Further molecular experiments confirmed the significant upregulation of glycogen phosphorylase (PYGL), phosphorylated PYGL (p-PYGL), and glycogen debranching enzyme (AGL) at the protein level during the daytime. Overall, we concluded that the downregulation of insulin secretion in the daytime under TRF mode facilitated glycogenolysis, contributing to the structural stability of glycogen α-particles.
DOI
10.1016/j.ijbiomac.2024.134225
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Comments
Ma, Z. W., Mou, J. Y., Yuan, Q., Wang, Z. Y., Liu, Q. H., Deng, B., ... & Wang, L. (2024). Molecular exploration of the diurnal alteration of glycogen structural fragility and stability in time-restricted-feeding mouse liver. International Journal of Biological Macromolecules, 277, 134225. https://doi.org/10.1016/j.ijbiomac.2024.134225