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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., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Molecular mechanisms behind structural alterations between fragile and stable glycogen α particles in liver are not clear yet. In this pilot study, we re-examined the diurnal alterations of glycogen structure from the perspective of liver tissue transcriptome. By comparing the structures of liver glycogen from mice at 12 am, 8 am, 12 pm, and 8 pm (light-on: 6 am; light-off: 6 pm), we re-confirmed that the liver glycogen was fragile at 12 am and 8 am and stable at 12 pm and 8 pm as previously reported. The structural differences of glycogen particles at 12 am and 12 pm were thoroughly compared via transcriptomics. Differentially expressed genes (DEGs) with statistical significance were identified, while expression level of the gene ppp1r3g (log 2 Fold_Change = -6.368, P-value = 2.89E-04) that encoded PPP1R3G with glycogen binding domain was most significantly changed, which provided preliminary clues to the structural alterations of glycogen α particles during the diurnal cycle., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Currently, there exist a variety of glycogen extraction methods, which either damage glycogen spatial structure or only partially extract glycogen, leading to the biased characterization of glycogen fine molecular structure. To understand the dynamic changes of glycogen structures and the versatile functions of glycogen particles in bacteria, it is essential to isolate glycogen with minimal degradation. In this study, a mild glycogen isolation method is demonstrated by using cold-water (CW) precipitation via sugar density gradient ultra-centrifugation (SDGU-CW). The traditional trichloroacetic acid (TCA) method and potassium hydroxide (KOH) method were also performed for comparison. A commonly used lab strain, Escherichia coli BL21(DE3), was used as a model organism in this study for demonstration purposes. After extracting glycogen particles using different methods, their structures were analyzed and compared through size exclusion chromatography (SEC) for particle size distribution and fluorophore-assisted capillary electrophoresis (FACE) for linear chain length distributions. The analysis confirmed that glycogen extracted via SDGU-CW had minimal degradation.

Human milk stands as the optimal natural source of nutrition for infants, harboring a plethora of complex nutrients including water, carbohydrates, lipids, minerals, proteins, and vitamins, as well as a diverse array of bioactive molecules such as oligosaccharides and growth factors, etc. These components facilitate and safeguard the growth and development of infants. Furthermore, the composition and concentration of human milk subtly evolve across different stages of breastfeeding, adapting to the specific requirements of infants. Therefore, attaining a more precise and comprehensive understanding of human milk composition holds significant value. In this study, a succinct overview of the primary constituents of human milk and their fluctuations during various lactation periods was provided. Then, existing research is critically examined concerning the existence of free glycogen in raw human milk because previous studies indicate the presence of glycogen in human milk but do not determine whether glycogen exists in free form. Glycogen within human milk may exert influence on the growth, development, and establishment of the immune system in infants, but precise mechanisms must be determined. Elucidation of the existing form of glycogen particles in human milk will not only update our understanding of human milk composition, but will also strengthen the roles of glycogen in infant development. Through our exploration, the presence of free glycogen in human milk appears plausible. However, further experiments are needed to confirm the claim via solid evidence. • Vital components of human milk at various lactational phases are outlined. • Physiological functions of glycogen in human milk is succinctly summarized. • Presence or absence of free glycogen in human milk is critically examined. [ABSTRACT FROM AUTHOR]

Growing evidence confirms associations between glycogen metabolic re-wiring and the development of liver cancer. Previous studies showed that glycogen structure changes abnormally in liver diseases such as cystic fibrosis, diabetes, etc. However, few studies focus on glycogen molecular structural characteristics during liver cancer development, which is worthy of further exploration. In this study, a rat model with carcinogenic liver injury induced by diethylnitrosamine (DEN) was successfully constructed, and hepatic glycogen structure was characterized. Compared with glycogen structure in the healthy rat liver, glycogen chain length distribution (CLD) shifts towards a short region. In contrast, glycogen particles were mainly present in small-sized β particles in DEN-damaged carcinogenic rat liver. Comparative transcriptomic analysis revealed significant expression changes of genes and pathways involved in carcinogenic liver injury. A combination of transcriptomic analysis, RT-qPCR, and western blot showed that the two genes, Gsy1 encoding glycogen synthase and Gbe1 encoding glycogen branching enzyme, were significantly altered and might be responsible for the structural abnormality of hepatic glycogen in carcinogenic liver injury. Taken together, this study confirmed that carcinogenic liver injury led to structural abnormality of hepatic glycogen, which provided clues to the future development of novel drug targets for potential therapeutics of carcinogenic liver injury. [Display omitted] [ABSTRACT FROM AUTHOR]

It has been reported that glycogen in Escherichia coli has two structural states, that is, fragility and stability, which alters dynamically. However, molecular mechanisms behind the structural alterations are not fully understood. In this study, we focused on the potential roles of two important glycogen degradation enzymes, glycogen phosphorylase (glgP) and glycogen debranching enzyme (glgX), in glycogen structural alterations. The fine molecular structure of glycogen particles in Escherichia coli and three mutants (Δ glgP , Δ glgX and Δ glgP /Δ glgX) were examined, which showed that glycogen in E. coli Δ glgP and E. coli Δ glgP /Δ glgX were consistently fragile while being consistently stable in E. coli Δ glgX , indicating the dominant role of GP in glycogen structural stability control. In sum, our study concludes that glycogen phosphorylase is essential in glycogen structural stability, leading to molecular insights into structural assembly of glycogen particles in E. coli. [Display omitted] [ABSTRACT FROM AUTHOR]