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肝脏ASPG介导的lysophosphatidylinositol催化作用会影响胰岛素信号转导

Feiyan Li¹, Hua-Sheng Huang², Qingwen Zhao³

¹Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences; Fudan University, 200032, Shanghai, China.

The EMBO journal

|August 4, 2025

概括

阿斯帕拉金合成酶 (ASPG) 调节脂肪酸处理和胰岛素敏感性. 降低ASPG通过改变生物活性脂质来改善胰岛素敏感性,为代谢疾病提供新的治疗点.

科学领域:

生物化学生物化学
代谢性疾病研究研究.
脂质代谢脂质代谢是一种

背景情况:

生物活性甘油脂 (GLPs) 导致与代谢功能障碍相关的脂肪性肝病 (MASLD) 和肥胖.
将GLP与胰岛素信号改变联系在一起的机制尚未完全理解.

研究的目的:

确定全身脂肪酸处理和胰岛素信号传递的新型调节剂.
研究阿斯巴拉金酶 (ASPG) 在代谢功能障碍和胰岛素耐药性中的作用.

主要方法:

对人类肝脏ASPG表达和胰岛素敏感性的相关分析.
在MASLD小鼠模型中对Aspg的基因操纵.
在体外和体内生化分析以确定ASPG的酶活性.
细胞内脂质积累和信号通路调节的分析.

主要成果:

肝脏ASPG表达与人体胰岛素敏感性相反相关.
在MASLD小鼠中,Aspg缺乏通过改变肝脏肝激素分泌来增强全身胰岛素敏感性.
ASPG 显示了对 lysophosphatidylinositol (LPI) 的 lysophospholipase 活性.
Aspg 缺乏导致LPI积累,PTP1B 抑制,并减少SEPP1分泌,促进胰岛素敏感性.

结论:

ASPG是生物活性脂质代谢和胰岛素信号的关键调节者.
通过ASPG控制LPI水平影响PTP1B活动和FOXO1依赖的SEPP1表达.
这一途径代表了一种将脂质代谢与全身胰岛素敏感性联系起来的新机制,并为葡萄糖平衡障碍提供治疗潜力.

关键词:

这是ASPG和ASPG.胰岛素信号传递 Lysophosphatidylinositol 的使用方法 lysophospholipase 是一种光脂酶.这就是PTP1B.

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