AMPK在心房代谢恒温和基质偏好的作用
bioRxiv : the preprint server for biology
|September 11, 2024
概括
在心房中AMP激活蛋白激酶 (AMPK) 损失会破坏脂肪酸氧化,促进pyruvate的使用,并可能导致心房动. 这种代谢转变凸显了AMPK在维持心房平衡中的作用.
科学领域:
- 心血管生理学心血管生理学
- 代谢调节 代谢调节 代谢调节
- 线粒体生物学 线粒体生物学
背景情况:
- 心房动 (AF) 是一种与代谢压力相关的常见心律失常.
- AMP激活蛋白激酶 (AMPK) 是一个关键的代谢传感器.
- 在小鼠中,心房特异性的AMPK缺失导致心房重塑和AF,这表明它在维持心房电气和结构稳定性方面的作用.
研究的目的:
- 为了调查心房基质对线粒体氧化物的偏好.
- 阐明AMPK在调节心房代谢中的作用.
- 了解AMPK删除如何影响心房代谢通路和恒温.
主要方法:
- 使用液体染色学-并联质谱法 (LC-MS/MS).
- 在有意识的小鼠中给药稳定同位素标记物 ([13C6]葡萄糖和[13C4]β-基酸盐).
- 进行了蛋白质组学分析和量化了乙-CoAs和基因转录表达.
主要成果:
- 对心房AMPK的条件删除将线粒体代谢从脂肪酸氧化转移到酸氧化.
- 心房长链乙基-CoA和低调脂肪酸吸收/氧化蛋白 (LPL,CD36,FABP3) 的降低.
- 减少PGC1-α和下游PGC1-α/PPARα/RXR调节基因的表达;在禁食时增加葡萄糖摄取和GLUT1表达.
结论:
- 心房AMPK对于维持心房代谢平衡至关重要.
- 对心房AMPK的损失导致PGC1-α/PPARα通路的降低调节和代谢重编程,有利于比脂肪酸更喜欢pyruvate.
- 这种从脂肪酸氧化转移的代谢转移可能会导致心房重塑和心房的发展.
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