通过GPR84介导的信号传导通过促进棕色脂肪细胞活性来影响代谢功能
Xue-Nan Sun1, Yu A An1,2, Vivian A Paschoal1
1Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
The Journal of clinical investigation
|October 19, 2023
概括
G蛋白结合受体84 (GPR84) 在棕色脂肪组织 (BAT) 活性中起着关键作用. 其缺乏会损害线粒体功能,导致代谢问题,但GPR84激活可能具有治疗潜力.
科学领域:
- 代谢研究的研究.
- 脂肪组织生物学 脂肪组织生物学
- 线粒体功能 线粒体功能
背景情况:
- G蛋白结合受体84 (GPR84),一种中链脂肪酸受体,与代谢条件有关.
- GPR84在代谢调节中的特定作用和机制尚未完全理解.
研究的目的:
- 研究GPR84在棕色脂肪组织 (BAT) 功能中的作用.
- 阐明GPR84影响BAT活动和能量代谢的机制.
主要方法:
- 使用了GPR84淘汰赛 (GPR84-KO) 的小鼠和野生型 (WT) 的 littermates.
- 使用原始棕色脂肪细胞进行了体外研究.
- 评估的BAT是脂质积累,发热基因表达,氧气消耗和细胞内水平.
- 使用一个GPR84激动剂 (6-n-octylaminouracil,6-OAU).
主要成果:
- GPR84-KO小鼠显示了BAT脂质积累的增加,BAT活性降低,以及对寒冷的敏感性增加.
- 来自GPR84-KO小鼠的初级棕色脂肪细胞表现出降低了发热基因表达和减少了氧气消耗.
- 在实验室中,GPR84激动剂 (6-OAU) 治疗恢复了棕色脂肪细胞的活性.
- GPR84激活增加了细胞内Ca2+水平,影响了线粒体呼吸.
结论:
- 在棕色脂肪组织中,GPR84具有强烈的表达和功能意义.
- 线粒体功能障碍是GPR84缺乏小鼠的BAT异常的基础.
- GPR84调节线粒体Ca2+水平和呼吸,影响BAT活动.
- GPR84代表了代谢障碍的潜在治疗标.
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