| Blocking glycogen synthase 1 in white adipose tissue alleviates hypermetabolism following severe burn injury through inhibition of JAK2 by UDPG |
| 論文作者 |
Zhuo, SX; Wang, ZN; Yang, LZX; Yuan, YX; Hu, DH; Chen, Y |
| 期刊/會(huì)議名稱 |
CELL REPORTS |
| 論文年度 |
2025 |
| 論文類別 |
|
| 摘要 |
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. |
| 卷 |
44 |
| 影響因子 |
6.9 |
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