在胰岛素耐药状态下,线粒体体氧化受损
Elric Zweck1, Sarah Piel2, Johannes W Schmidt2
1Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Munich, Neuherberg, Germany; Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; CARID, Cardiovascular Research Institute Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
使用体的线粒体功能在2型糖尿病和肥胖等胰岛素抵抗状态下降. 这种受损的体氧化突显了代谢不灵活性,并为疾病评估提供了新的指标.
科学领域:
- 生物化学 生物化学
- 代谢生理学 代谢生理学
- 线粒体生物学 线粒体生物学
背景情况:
- 线粒体呼吸功能减少与代谢障碍有关,如2型糖尿病 (T2D),肥胖和代谢功能障碍相关的脂肪性肝病 (MASLD).
- 这些情况与胰岛素耐药性和代谢灵活性受损有关.
- 体 (KBs),如β-基酸盐 (HBA) 和乙酸盐 (ACA) 在推动这些状态中的线粒体氧化酸化 (OXPHOS) 的作用尚未完全理解.
研究的目的:
- 研究HBA和ACA对关键代谢器官中OXPHOS容量的差异性贡献.
- 在T2D,肥胖和MASLD的人类和小鼠模型中评估KB驱动的OXPHOS.
- 为了确定KB氧化是否反映了胰岛素抵抗条件下的线粒体代谢灵活性受损.
主要方法:
- 使用高分辨率的有针对性的呼吸计协议.
- 分析了心脏,骨肌肉,脏和肝脏组织中的OXPHOS容量.
- 在不同的人类和小鼠队伍中比较KB利用率,代表T2D,肥胖和MASLD.
主要成果:
- 与对照人群相比,KB驱动的OXPHOS容量在患有T2D的人群中明显较低 (心脏中约30%,骨肌肉中约25%相对).
- 肥胖小鼠对脏OXPHOS的绝对和相对KB贡献降低 (~15%).
- 患有肝硬化症的肥胖人群表现出29%较低的肝脏HBA驱动OXPHOS容量.
结论:
- 线粒体KB驱动的OXPHOS在胰岛素抵抗状态下,在各种器官的绝对和相对值中受到损害.
- 这种损伤可能反映了线粒体代谢灵活性减少.
- KB呼吸计可以作为T2D,肥胖和MASLD中线粒体功能障碍的敏感指标.
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