FFAR4驱动干细胞的命运向脂质和铁储存肠细胞,保护人类肠体免受铁灭
Mona Farhadipour1, Hui Leng1, Theo Thijs1
1Gut Peptide Research Lab, Translational Research for Gastrointestinal Disorders (TARGID), KU Leuven, Gasthuisberg O&N1, P. O. Box 701, Leuven, 3000, Belgium.
Stem cell research & therapy
|December 2, 2025
概括
在肠干细胞 (ISC) 中的自由脂肪酸受体4 (FFAR4) 激活促进正常体重个体的脂质处理,但在肥胖中受损. 这突显了FFAR4的价值.
科学领域:
- 胃肠病学 胃肠病学
- 干细胞生物学 干细胞生物学
- 代谢研究研究 代谢研究
背景情况:
- 肠干细胞 (ISC) 的命运受到通过表面受体的微环境线索的影响.
- 脂质感应受体FFAR4在ISC调节中的作用尚未完全理解.
- 在肥胖的高脂环境中,FFAR4功能可能会发生变化.
研究的目的:
- 研究FFAR4在调节ISC命运中的功能作用.
- 为了确定肥胖患者的FFAR4功能是否受损.
主要方法:
- 人类小肠器官 (肠体) 来自正常体重的捐赠者和肥胖患者.
- 在这些类动物中研究了FFAR4激活.
主要成果:
- 在正常体重的体体中,FFAR4激活促进了吸收性体细胞分化,增加了脂质液滴的形成和铁的储存,降低了ferroptosis的易受性.
- 肥胖患者的肠膜中FFAR4的激活未能改变上皮质的组成或功能,这表明信号受损.
- 素产生没有受到影响,但MEK1/2抑制阻断了FFAR4诱导的变化.
结论:
- 干细胞上的化学感知受体显著影响肠道上皮质的组成和功能.
- 在ISC分化和脂质代谢中,FFAR4起着关键作用.
- 肥胖症中FFAR4信号受损可能导致肠道上皮功能改变.
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