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WFS1-ZnT3-Zn2+轴调节肥胖和抑郁症的恶性循环
Mengting Gong1, Yulin Fang1, Kaijiang Yang1
1Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|September 11, 2024
概括
神经沃尔夫拉明类内细胞网膜蛋白1 (WFS1) 缺乏会使肥胖和抑郁症恶化. WFS1调节神经 (Zn2+) 稳态,而瑞卢可以通过向WFS1-ZnT3-Zn2+轴来逆转这些情况.
科学领域:
- 神经科学是一个神经科学.
- 代谢障碍 代谢障碍 代谢障碍
- 细胞生物学 细胞生物学
背景情况:
- 肥胖和抑郁症是全球重要的健康问题,神经连接的理解不佳.
- 神经沃尔夫拉明类内质网膜蛋白1 (WFS1) 在肥胖和抑郁之间的相互作用中发挥作用.
研究的目的:
- 为了阐明连接肥胖和抑郁的神经机制.
- 调查WFS1在这种关联中的作用.
- 为了探索riluzole的治疗潜力.
主要方法:
- 使用高脂肪饮食 (HFD) 的小鼠模型,具有神经特异性WFS1缺乏.
- 使用人类多能干细胞 (hESCs) 进行神经分化和大脑器官形成.
- 评估了神经原生细胞 (NPC) 中的 (Zn2+) 稳态,亡和脂毒性.
- 研究了瑞卢对ZnT3表达和NPC存活率的影响.
主要成果:
- 神经WFS1缺陷加剧了HFD小鼠的肥胖-抑郁循环.
- 发现WFS1通过在脂质代谢失调下抑制ZnT3来调节Zn2+稳态和NPC亡.
- 利卢调节ZnT3表达,维持的平衡,并保护NPC免受脂毒性.
- 里卢在体内给药改善了HFD诱导的肥胖和相关的抑郁症.
结论:
- 一个WFS1-ZnT3-Zn2+轴在肥胖和抑郁的恶性循环中至关重要.
- 缺少WFS1会破坏神经平衡,并促进NPC的亡.
- 利鲁通过准这一轴,显示出逆转肥胖和抑郁症的潜力.
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