在巨细胞编程和元炎症中的营养感应生长激素分泌剂受体
Da Mi Kim1, Jong Han Lee2, Quan Pan1
1Department of Nutrition, Texas A&M University, College Station, TX 77843, USA.
Molecular metabolism
|December 13, 2023
概括
巨细胞生长激素分泌受体 (GHSR) 驱动着与肥胖相关的炎症和胰岛素抵抗. 阻止巨细胞中的GHSR减少炎症并改善代谢健康,这表明GHSR是治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢性疾病研究研究
- 内分泌学 在内分泌学.
背景情况:
- 肥胖相关的慢性炎症或超级炎症是导致肥胖相关并发症的主要原因之一.
- 生长激素分泌受体 (GHSR) 影响营养感知,食物摄入和脂肪沉积.
- 之前的研究表明,全球GHSR剥离可以防止饮食引起的炎症和胰岛素抵抗,但具体的细胞机制尚不清楚.
研究的目的:
- 在肥胖引起的元炎症的背景下,研究GHSR在巨细胞中的作用.
- 确定巨细胞中GHSR对炎症和胰岛素抵抗有所贡献的机制.
主要方法:
- 产生的骨髓特异性Ghsr淘汰赛小鼠 (LysM-Cre;Ghsr).
- 用高脂肪饮食 (HFD) 进行5个月的治疗,以诱导肥胖.
- 进行了体内代谢分析,葡萄糖/胰岛素耐受性测试和组织分析 (腹膜巨细胞,脂肪组织,肝脏).
- 使用骨髓衍生的巨细胞 (BMDMs) 进行了ex vivo研究,并使用巨细胞细胞系进行了体外研究.
主要成果:
- 吃HFD养的LysM-Cre;Ghsrf/f小鼠显示系统性炎症和胰岛素耐药性降低,而体重或食物摄入量没有变化.
- 宏细胞特异性GHSR缺陷降低了脂肪组织和肝脏中促炎性宏细胞的透和激活.
- 在体外,缺乏 Ghsr 的巨细胞表现出减少的炎症性两极分化,降低糖解和增加脂肪酸氧化.
- 发现GHSR通过PKA-CREB-IRS2-AKT2信号通路来调节巨细胞极化.
结论:
- 巨细胞GHSR是元炎症病变发生的关键调解者.
- 巨细胞中的GHSR促进巨细胞的透和促炎性两极分化.
- 向巨细胞GHSR为肥胖和相关代谢障碍提供了一个潜在的新型免疫治疗策略.
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