果糖的过度消费会损害肝脏的平衡和氨的处置
Jian-Hui Shi1, Yu-Xia Chen1, Yingying Feng1,2
1National Key Laboratory of Immunity & Inflammation and Department of Pathophysiology, Naval Medical University, Shanghai, China.
Nature communications
|December 1, 2023
概括
在小鼠中,高果糖摄入量会破坏肝脏的 (Mn) 水平和氨清除. 这通过ChREBP/Slc30a10通路发生,这表明饮食中的果糖限制可能有助于管理超血.
科学领域:
- 生物化学 生物化学
- 代谢途径 代谢途径
- 毒理学 毒理学 毒理学
背景情况:
- 阿基因酶对于肝脏中氨的处置至关重要.
- 果糖对 (Mn) 和氨代谢的影响尚不清楚.
- 肝脏Mn平衡对于肝脏功能至关重要.
研究的目的:
- 调查果糖过度消费对肝脏Mn稳态和氨代谢的影响.
- 阐明结合果糖,Mn和氨的分子机制.清除氨.
- 探索饮食中果糖限制对高氨血的治疗潜力.
主要方法:
- 使用过度暴露于果糖的雄性小鼠模型.
- 评估肝脏的Mn含量,阿基纳酶活性和Mn-SOD活性.
- 在肝功能障碍条件下研究了氨清除.
- 检查了Mn出口商Slc30a10.10的基因转录
- 采用了Slc30a10和ChREBP的肝细胞特异性基因删除.
主要成果:
- 过度摄入果糖显著降低了肝脏的Mn含量和酶/Mn-SOD活性.
- 在患有肝功能障碍的果糖暴露的小鼠中观察到血液氨清除受损.
- 果糖通过一种依赖于ChREBP的机制在肝脏中激活了Slc30a10基因转录.
- 过度表达Slc30a10模仿果糖效应;Slc30a10或ChREBP的删除阻止了这些效应.
结论:
- 果糖消费对肝脏的Mn稳态和氨排放有负面影响.
- ChREBP/Slc30a10通路调解果糖对和氨代谢的影响.
- 饮食中的果糖限制被提议作为预防和治疗高氨血症的策略.
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