2025-11-21 中国科学院(CAS)
<関連情報>
- https://english.cas.cn/newsroom/research_news/life/202511/t20251124_1133085.shtml
- https://www.cell.com/cell-reports/fulltext/S2211-1247(25)01349-X
白色脂肪組織におけるグリコーゲン合成酵素1の阻害は、UDPGによるJAK2の阻害を介して重度の火傷後の代謝亢進を軽減する Blocking glycogen synthase 1 in white adipose tissue alleviates hypermetabolism following severe burn injury through inhibition of JAK2 by UDPG
Shixuan Zhuo ∙ Zinan Wang ∙ Lanzexin Yang ∙ Yixuan Yuan ∙ Dahai Hu ∙ Yan Chen
Cell Reports Published:November 18, 2025
DOI:https://doi.org/10.1016/j.celrep.2025.116577
Graphical abstract
Highlights
- Deletion of Gys1 suppresses burn-induced thermogenesis in WAT and mitigates fatty liver
- Gys1 deletion elevates UDPG, which attenuates signaling of interleukin-6 after burn injury
- UDPG directly interacts with JAK2 and inhibits STAT3 phosphorylation
- Administration of a small-molecule inhibitor of GYS1 suppresses post-burn hypermetabolism
Summary
Browning of white adipose tissue (WAT) contributes to the sustained hypermetabolism observed in patients with burns. How glycogen metabolism in WAT is linked to burn-induced hypermetabolism remains unknown. We discover that burn-induced UCP1 expression in subcutaneous WAT is accompanied by elevation of glycogen synthase 1 (GYS1). Adipose tissue-specific deletion of Gys1 suppresses burn-induced UCP1 expression. Gys1 deletion inhibits WAT lipolysis and mitigates hepatic steatosis. Mechanistically, the effects of Gys1 deletion on burn-induced hypermetabolism are mediated by an increase in uridine diphosphate glucose (UDPG), the substrate of GYS1. Both Gys1 deletion and UDPG administration attenuate signaling of interleukin-6. UDPG directly interacts with JAK2 and inhibits STAT3 phosphorylation. Administration of MZ-101, a small-molecule inhibitor of GYS1, suppresses post-burn hypermetabolism and improves the survival rate of mice. Our findings uncover the regulatory role of the GYS1-UDPG-JAK2-STAT3 cascade in WAT during post-burn hypermetabolism and underscore the potential of GYS1 inhibition as a therapeutic strategy for burn injury.
