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中间前视区域FoxO1以性二态的方式控制代谢适应

Pei Luo^1,2, Xiaohua Yang^1,2, Qi Xu^1,3

¹Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Illinois Chicago, Chicago, IL, 60612, USA.

bioRxiv : the preprint server for biology

|July 16, 2025

概括

在中部前视区域 (MPOA) 的叉头转录因子O1 (FoxO1) 调节代谢适应. 在女性中,减少的FoxO1可以防止肥胖,增强发热和能源消耗.

科学领域:

神经内分泌学神经内分泌学
代谢调节代谢调节代谢调节
热调节热调节热调节

背景情况:

中间前视区域 (MPOA) 对于代谢适应环境压力因素至关重要.
控制MPOA在代谢适应中的作用的分子机制尚未完全理解.
叉头转录因子O1 (FoxO1) 是已知的压力适应的调解者.

研究的目的:

研究MPOA中FoxO1在对温度和营养挑战的代谢反应中的作用.
阐明FoxO1在代谢适应中的性别特异性作用.

主要方法:

在MPOA神经元中利用了FoxO1的特定删除 (FoxO1-KO^MPOA) 或构成激活 (FoxO1-CA^MPOA) 的小鼠模型.
评估的新陈代谢参数包括体重,身体成分,食物摄入量和高脂肪饮食 (HFD) 和寒冷暴露 (6°C) 的能量消耗.
研究了卵巢切除 (OVX) 和17β-雌激素对FoxO1-介导的防治饮食引起的肥胖 (DIO) 的影响.

主要成果:

在雌性小鼠的MPOA中,HFD挑战降低了FoxO1表达,但不是雄性小鼠.
在MPOA神经元中FoxO1删除 (FoxO1-KO^MPOA) 保护雌性小鼠免受HFD诱导的肥胖症 (DIO),增加瘦质量,热生成和能量消耗,同时减少食物摄入量.
通过卵巢切除 (OVX) 取消了这种保护,并且独立于雌激素.
在MPOA神经元中FoxO1的构成性激活 (FoxO1-CA^MPOA) 在两性中都加剧了DIO易感性.
FoxO1-KO^MPOA在6°C的女性中增强了感冒诱导的热生成,而在热中性 (30°C) 时则没有这种效果.

结论:

在MPOA中的FoxO1在协调新陈代谢适应营养和温度挑战方面发挥着关键的,性别特异性的作用.
在MPOA中减少的FoxO1通过雌激素独立机制在雌性小鼠中提供了对DIO的保护.
FoxO1^MPOA是热生成和能量平衡的关键调节者,特别是在女性对环境压力因素的反应中.

关键词:

在FoxO1中,FoxO1是FoxO1的第一个代号.这就是MPOAA.性别差异的性别差异.

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