27-基胆固醇作用于受体α,由弧形核中的POMC神经元表达,以调节养行为
Hui Ye1,2, Xiaohua Yang2,3, Bing Feng4
1School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 639798, Singapore.
Science advances
|July 12, 2024
概括
胆固醇代谢物27-胆固醇 (27HC) 通过激活大脑雌激素受体 (ERα) 和POMC神经元来降低食欲. 这一途径抑制食物摄入,作为高胆固醇水平的反机制.
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
- 胆固醇的新陈代谢
背景情况:
- 氧化醇,胆固醇代谢物,调节胆固醇平衡.
- 27-胆固醇 (27HC) 是一种丰富的氧胆固醇,可以穿过血脑屏障.
- 27HC作为一种内源性选择性雌激素受体调节剂.
研究的目的:
- 调查27HC与大脑雌激素受体α (ERα) 结合,以调节能量平衡的假设.
- 阐明27HC影响食物摄入和神经元活动的机制.
主要方法:
- 在动物模型中,直接向大脑输送27HC.
- 评估食物摄入量和神经元激活 (POMC).
- 利用ERα抑制,POMC神经元中的ERα删除和POMCARH神经元的化学遗传抑制.
- 研究小导电激活 (SK) 通道的作用.
主要成果:
- 大脑输送的27HC减少了食物摄入量,并以ERα依赖的方式激活了POMCARH神经元.
- 大脑ERα或POMCARH神经元的抑制消除了27HC的厌食性作用.
- 27HC通过抑制SK通道来刺激POMCARH神经元.
结论:
- 27HC通过ERα中心作用,减少食物摄入量.
- 在POMCARH神经元中的27HC-ERα-SK通道通路调节能量平衡.
- 这一途径代表了对高循环胆固醇的负反机制.
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