@article{Wang2026, 
author = {Ziyi Wang and Shasha He and Bi Fang and Renjie Feng and Wenshao Li and Liang Wang and Chaoxin Man and Huifan Yu and Fei Li and Mitchell A. Sullivan and Na Wang and Robert G. Gilbert and Peng Cao},
title = {Glycogen Architecture Dysregulation in Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Therapeutic Avenue via Glycogen Homeostasis},
year = {2026},
journal = {Food Science and Human Wellness},
keywords = {Glycogen, MASH, MASLD, polyphenols},
url = {https://www.sciopen.com/article/10.26599/FSHW.2026.9251296},
doi = {10.26599/FSHW.2026.9251296},
abstract = {Metabolic dysfunction-associated steatohepatitis (MASH) is the inflammatory phase of the metabolic dysfunction-associated steatotic liver disease (MASLD) spectrum, and can progress to fibrosis and even carcinoma; currently, there are few effective therapies. The complex branched glucose polymer glycogen is found in significant quantities in the liver; it comprises “β particles”, ~20 nm in size, bound as aggregate “α particles”, up to hundreds of nm in size. The role of liver glycogen in MASLD and MASH is unknown. Size-exclusion chromatography, fluorophore-assisted carbohydrate electrophoresis and transmission electron microscopy show that, compared with healthy controls, MASLD livers exhibited a higher β-particle content (32.6% vs 40.7%, P <0.05) and a 5 % longer average chain length (ACL); MASH amplified these defects: β-particle fraction rose to 46.1% (P <0.001 vs. control) and ACL to 26 % (P <0.0001 vs. control), indicating this is an early, shared disruption in different stages of MASLD. The glycogen-related proteins (AGL, GBE, GYS, PYGL and PPP1R3B) exhibit opposite trajectories in MASLD and MASH. Therapeutic dietary polyphenols, despite disparate effects on individual glycogen-related enzymes, all reversed aberrant glycogen architecture by increasing α-particle proportions and decreasing chain lengths. Our findings offer a mechanistic blueprint whereby glycogen structure characterization might guide clinical therapeutic strategy.}
}