Scholarlink

<p>Severe burn injury induces a prolonged hypermetabolic state that is associated with undesirable metabolic consequences. Heat shock factor 1 (HSF1) is the predominant transcription factor that responds to thermal stress and has been reported to orchestrate the browning gene program of subcutaneous white adipose tissue (sWAT), thereby promoting energy expenditure. However, the role of sWAT HSF1 in the pathogenesis of burn injury remains unclear. In this study, we report that burn injury notably upregulates the expression of HSF1 in sWAT. Moreover, the genetic ablation of HSF1 in adipose tissues attenuated the burn-induced sWAT browning and lipolysis, circulating lipid dysfunction, and liver injury. Conversely, specific overexpression of the active form of HSF1 in sWAT exacerbated these phenotypes. Notably, we found that burn injury largely suppressed sWAT smooth muscle-related gene programs and shifted toward browning gene programs. Mechanistically, HSF1, in cooperation with PRDM16, drives this phenotypic switch by directly inhibiting the expression of Myh11, which is the smooth muscle marker for sWAT reprogramming. Furthermore, the pharmacological inhibition of HSF1 with DTHIB ameliorated burn injury. Overall, these findings highlight that sWAT HSF1 is a key mediator of pathological hypermetabolism following severe burn injury.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

HSF1 inhibits smooth muscle gene program to enhance white fat browning and hypermetabolism after burn injury

  • 期刊论文

  • 发表日期：

    2026年5月7日

查看全文
  • Yankang Zhang,
  • Yuhan Zheng,
  • Bin Chen,
  • Xinqian Li,
  • Ting Zhang,
  • Lingyan Xu,
  • Jing Ma,
  • Xinran Ma,
  • Yu Li

摘要

Severe burn injury induces a prolonged hypermetabolic state that is associated with undesirable metabolic consequences. Heat shock factor 1 (HSF1) is the predominant transcription factor that responds to thermal stress and has been reported to orchestrate the browning gene program of subcutaneous white adipose tissue (sWAT), thereby promoting energy expenditure. However, the role of sWAT HSF1 in the pathogenesis of burn injury remains unclear. In this study, we report that burn injury notably upregulates the expression of HSF1 in sWAT. Moreover, the genetic ablation of HSF1 in adipose tissues attenuated the burn-induced sWAT browning and lipolysis, circulating lipid dysfunction, and liver injury. Conversely, specific overexpression of the active form of HSF1 in sWAT exacerbated these phenotypes. Notably, we found that burn injury largely suppressed sWAT smooth muscle-related gene programs and shifted toward browning gene programs. Mechanistically, HSF1, in cooperation with PRDM16, drives this phenotypic switch by directly inhibiting the expression of Myh11, which is the smooth muscle marker for sWAT reprogramming. Furthermore, the pharmacological inhibition of HSF1 with DTHIB ameliorated burn injury. Overall, these findings highlight that sWAT HSF1 is a key mediator of pathological hypermetabolism following severe burn injury.