Scholarlink

<p>MASH is a leading cause of liver transplantation. Here, we investigated formoterol, a long-acting β2 adrenergic receptor agonist (LABA), in MASH. Mice treated with a high-fat diet (HFD) for sixteen weeks developed liver steatosis and were treated with formoterol or vehicle for four weeks. Steatosis largely resolved following formoterol treatment. To investigate mechanism, we evaluated mitochondrial biogenesis and found in HFD mice treated with formoterol versus vehicle that: PGC1α levels and electron transport chain components were significantly higher; mitochondrial number was increased; and lipids were decreased. Human HepaRG liver cells were then exposed to free fatty acids and/or formoterol. Formoterol attenuated lipid accumulation and increased ATP-linked basal and maximal respiration. Finally, a retrospective analysis of 59,644 patients with MASH showed that patients taking LABAs had fewer complications of advanced liver disease and lower mortality. Together, these data raise the possibility that LABAs, especially formoterol, could be a novel MASH treatment.</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

Beta 2 adrenergic receptor agonists as a treatment for metabolic dysfunction-associated steatohepatitis (MASH)

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月25日

查看全文
  • Brennan S. Winkler,
  • Kristina M. Stayer,
  • Abhinav K. Rao,
  • Ehtesham Arif,
  • Tsultrim T. Mendenhall,
  • Kristy L. Thomas,
  • Kylie R. Driggers,
  • Xiaofeng Zuo,
  • Wayne Fitzgibbon,
  • Peifeng Deng,
  • Yanhui Su,
  • Yujing Dang,
  • Marie Gerges,
  • Daniel Kagan,
  • Vishwajeeth Pasham,
  • Bethany Wolf,
  • Don C. Rockey,
  • Jessica H. Hartman,
  • Joshua H. Lipschutz

摘要

MASH is a leading cause of liver transplantation. Here, we investigated formoterol, a long-acting β2 adrenergic receptor agonist (LABA), in MASH. Mice treated with a high-fat diet (HFD) for sixteen weeks developed liver steatosis and were treated with formoterol or vehicle for four weeks. Steatosis largely resolved following formoterol treatment. To investigate mechanism, we evaluated mitochondrial biogenesis and found in HFD mice treated with formoterol versus vehicle that: PGC1α levels and electron transport chain components were significantly higher; mitochondrial number was increased; and lipids were decreased. Human HepaRG liver cells were then exposed to free fatty acids and/or formoterol. Formoterol attenuated lipid accumulation and increased ATP-linked basal and maximal respiration. Finally, a retrospective analysis of 59,644 patients with MASH showed that patients taking LABAs had fewer complications of advanced liver disease and lower mortality. Together, these data raise the possibility that LABAs, especially formoterol, could be a novel MASH treatment.