在脂肪组织和肝脏中由骨质松丁驱动的T细胞积累和功能促进了胰岛素抵抗和MAFLD
Frédéric Soysouvanh1, Déborah Rousseau1, Stéphanie Bonnafous2
1Université Côte d'Azur, INSERM, U1065, C3M, Nice, France.
Obesity (Silver Spring, Md.)
|September 19, 2023
概括
骨质松丁 (SPP1) 通过调节T细胞积累和两极分化来驱动与肥胖相关的炎症和胰岛素抵抗. 向SPP1可能为代谢功能障碍和脂肪肝疾病提供治疗益处.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢疾病 代谢疾病
- 分子生物学分子生物学
背景情况:
- 肥胖会引发脂肪组织炎症,胰岛素抵抗 (IR),以及与代谢相关的脂肪肝疾病 (MAFLD).
- 在与肥胖相关的代谢功能障碍期间,骨质松丁/分泌蛋白1 (SPP1) 在调解T细胞反应中的作用尚未完全理解.
研究的目的:
- 为了研究SPP1对T细胞调节在肥胖驱动的脂肪组织炎症的贡献.
- 评估SPP1对巨细胞透,IR和MAFLD发展的影响.
主要方法:
- 在人类脂肪组织和肝脏样本中评估了SPP1和T细胞标志物表达,这些样本来自肥胖,2型糖尿病和MAFLD患者.
- 利用高脂肪饮食中的Spp1-knockout小鼠评估SPP1在T细胞功能和代谢参数中的作用.
主要成果:
- 在患有肥胖的人群中,SPP1升高与T细胞标志物 (CD4,CD8A) 和IR增加相关. 减肥减少了SPP1和CD8A的表达.
- 在小鼠中,SPP1缺乏改善了脂肪组织的IR,通过防止炎症前的T细胞积累和促进调节性T细胞.
- 缺乏SPP1减少了T细胞向Th1的偏向,并显著改善了与肥胖相关的肝硬化和炎症.
结论:
- SPP1关键调节T细胞积累和两极分化,启动肥胖驱动的慢性炎症.
- 在疾病过程的早期针对SPP1可能是对IR和MAFLD的有希望的治疗策略.
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