在PKM2寡合状态的转变指示脂肪细胞的炎症潜力
Michelle Sma Damen1,2, Pablo C Alarcon1,2,3,4, Calvin C Chan1,2,3,5,6
1Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
JCI insight
|November 24, 2025
概括
I型干扰素 (IFN-I) 通过改变白色脂肪细胞代谢来驱动肥胖的炎症. 向酸盐激酶M2 (PKM2) 减少了这种炎症和代谢疾病的严重程度在肥胖的小鼠和人类.
科学领域:
- 代谢性疾病是一种代谢性疾病.
- 免疫学 免疫学 免疫学
- 脂肪细胞生物学 脂肪细胞生物学
背景情况:
- 白色脂肪细胞的炎症功能尚未完全理解.
- 肥胖与增加的全身和组织炎症有关.
研究的目的:
- 研究I型干扰素 (IFN-I) 在脂肪细胞代谢和炎症中的作用.
- 探索pyruvate kinase异酶M2 (PKM2) 作为治疗肥胖相关炎症的治疗点.
主要方法:
- 研究了IFN-I对脂肪细胞糖解,NAD+利用和PKM2功能的影响.
- 利用化学和遗传抑制糖解,NAD+救援途径和PKM2在体外和体内.
- 从具有和没有代谢疾病的个体的白色脂肪组织中分析了基因表达.
- 在肥胖小鼠和初级人类脂肪细胞中测试了PKM2的小分子向.
主要成果:
- IFN-I信号促进脂肪细胞糖解,NAD+利用和PKM2功能,有助于炎症.
- 抑制糖解,NAD+救援或PKM2降低了IFN-I诱导的炎症性细胞因子的产生.
- 在体内准PKM2可降低肥胖小鼠的炎症和代谢疾病严重程度.
- 患有肥胖和代谢疾病的人类脂肪组织显示炎症基因表达增加.
- 抑制PKM2可降低原始人体脂肪细胞中的IFN-I驱动的炎症.
结论:
- IFN-I/PKM2轴与脂肪细胞炎症和肥胖中的代谢功能障碍有关.
- 向PKM2为调节与肥胖相关的炎症提供了潜在的治疗策略.
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