甲状腺激素通过在亚临床甲状腺功能低下症中触发巨细胞炎症来加剧胰岛素耐药性
Haihong Zhang1, Zekun Zeng1, Yan Liu1
1Department of Endocrinology and International Joint Research Center for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Experimental & molecular medicine
|June 16, 2025
概括
甲状腺刺激激素 (TSH) 通过促进巨细胞炎症来驱动胰岛素抵抗. 阻断髓状细胞中的TSH受体改善了代谢健康,揭示了亚临床甲状腺功能低下症的关键机制.
科学领域:
- 内分泌学 在内分泌学.
- 免疫学 免疫学 免疫学
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 亚临床甲状腺功能低下症与胰岛素抵抗有关,但潜在的机制尚不清楚.
- 巨细胞表达高水平的TSH受体 (TSHR),表明在调解TSH效应方面可能发挥作用.
研究的目的:
- 研究巨细胞中TSHR在胰岛素耐药性发展中的作用.
- 阐明TSH,巨细胞炎症和代谢功能障碍之间的机械联系.
主要方法:
- 建立了一个骨髓细胞特异性TSHR淘汰 (TshrMKO) 鼠标模型.
- 利用高脂肪饮食诱导的肥胖模型和与肝细胞,脂肪细胞和骨肌肉细胞的共同培养实验.
- 分析了巨细胞透,极化,细胞因子分泌和胰岛素信号通路.
主要成果:
- 与野生类型对照相比,TshrMKO小鼠的胰岛素敏感性得到改善,肥胖率降低.
- 巨细胞中TSHR缺陷降低了它们的M1极化和炎症性细胞因子 (IL-1α,IL-1β,IL-6) 分泌.
- 缺乏TSHR的巨细胞通过改善胰岛素信号来调节目标细胞中的葡萄糖代谢.
结论:
- 通过诱导巨细胞M1两极化和随后的炎症性细胞因子释放,TSH促进胰岛素耐药性,从而损害了目标组织中的胰岛素信号传递.
- 向巨细胞中的TSHR或阻断关键的炎症性细胞因子为与亚临床甲状腺功能低下症相关的代谢障碍提供了潜在的治疗策略.
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