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在白色脂肪组织棕色化过程中,通过ATF4-MTHFD2轴调节回氧稳态

Rehna Paula Ginting¹, Hoang-Anh Pham-Bui¹, Choijamts Munkhzul²

¹Department of Integrated Biomedical Science, Soonchunhyang University, Cheonan, 31151, South Korea.

|June 14, 2025

概括

寒冷暴露会在白色脂肪中线粒体生长之前触发热生成激活. 通过MTHFD2,ATF4蛋白通过MTHFD2维持氧化还原平衡,这对冷诱导的色和能量恒温至关重要.

科学领域:

线粒体生物学线粒体生物学
脂肪细胞的功能
代谢调节代谢调节代谢调节

背景情况:

氧化还原平衡对于线粒体健康至关重要.
白色脂肪细胞色涉及显著的线粒体变化.
在棕色化过程中控制线粒体氧化还原的机制在很大程度上是未知的.

研究的目的:

研究综合应激反应 (ISR) 信号在冷引起的白色脂肪细胞色中的作用.
在这个过程中阐明控制线粒体氧化还原平衡的机制.
为了确定热生成和脂肪组织中的能量消耗的关键调节者.

主要方法:

在具有脂肪细胞特异性ATF4删除的小鼠中,冷暴露模型.
对线粒体应激和ISR信号 (ATF4表达) 的分析.
评估能量消耗,核心体温和炎症.
使用特定抑制剂 (DS18561882) 和抗氧化剂 (MitoQ) 来研究MTHFD2的表达和功能.

主要成果:

热生成激活在寒冷诱导的色过程中先于线粒体生物发生.
暴露于寒冷会增加ATF4的表达,从而激活ISR信号.
矛盾的是,脂肪细胞特有的ATF4删除会增加能量消耗,但会降低体温并加剧炎症.
抗氧化剂MitoQ可以逆转ATF4缺乏的影响.
ATF4调节MTHFD2,这是NADPH生成和线粒体氧化还原恒温的关键酶.
抑制MTHFD2会损害冷气诱导的线粒体呼吸,模仿ATF4的损失.

结论:

在冷诱导iWAT棕色化过程中,ATF4对于通过MTHFD2维持氧化还原平衡至关重要.
ATF4-MTHFD2轴在调节线粒体功能和能量恒温中发挥着至关重要的作用.
向ATF4或MTHFD2可以为代谢障碍提供治疗策略.

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