人类半蛋白3种变体与黑色皮质蛋白电路的发展和能量平衡的联系
Agatha A van der Klaauw1, Sophie Croizier2, Edson Mendes de Oliveira1
1University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Cell
|January 22, 2019
概括
对于调节人体体重的脑电路的发展至关重要. SEMA3通路基因的遗传变异与严重肥胖有关,影响能量稳态.
科学领域:
- 神经科学
- 遗传学
- 代谢过程
背景情况:
- 低垂体黑色皮质神经元是体重的关键调节者.
- 半素3 (SEMA3) 信号通路影响神经电路的发展.
研究的目的:
- 调查SEMA3信号在下丘脑黑色素电路的发展中的作用.
- 确定SEMA3通路基因变异与严重肥胖之间的关联.
主要方法:
- 在肥胖个体和对照中对SEMA3A-G及其受体 (PLXNA1-4;NRP1-2) 的遗传分析.
- 斑马鱼的突变性查以评估Semaforin 3通路基因干扰对生长和脂肪的影响.
- 鼠标模型研究涉及删除Pro-opiomelanocortin神经元中的Neuropilin-2,以评估对神经元投射,能量消耗和体重的影响.
主要成果:
- 在严重肥胖的个体中发现了40种SEMA3通路基因的罕见变异,与对照个体相比,病例的丰富程度显著.
- 斑马鱼中Semaforin 3信号的破坏导致体质生长和/或脂肪增加.
- 在小鼠的Pro-opiomelanocortin神经元中删除Neuropilin-2导致对腹腔核投射的弧度受损,能量消耗减少和体重增加.
结论:
- 通过SEMA3传递信号对于下丘脑的黑色素回路的正常发育至关重要.
- 通过影响能量恒温,SEMA3信号的干扰有助于肥胖的发病.
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