Selective Survival of Sim1/MC4R Neurons in Diet-Induced Obesity.
Selective Survival of Sim1/MC4R Neurons in Diet-Induced Obesity.
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Sim1/MC4R 神经元在饮食引起的肥胖中的选择性存活。
DOI：
10.1016/j.isci.2020.101114
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发表时间：
2020
期刊：
影响因子：
5.8
通讯作者：
Baldini,Giulia
中科院分区：
文献类型：
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作者：
Nyamugenda,Eugene;Griffin,Haven;Russell,Susan;Cooney,KimberlyA;Kowalczyk,NicholasS;Islam,Ishrar;Phelan,KevinD;Baldini,Giulia
在黑皮质素途径中，黑皮质素-4受体（MC 4 R）的功能是控制能量稳态。MC 4 R在Sim 1神经元的亚群（Sim 1/MC 4 R神经元）中表达，并在下丘脑室旁核（PVN）中起控制食物摄入的作用。定位肥胖症患者下丘脑损伤的部位对于对抗这种疾病至关重要。在饮食诱导肥胖（DIO）的雄性和雌性小鼠的PVN中，存在神经元损失。然而，现有的PVN Sim 1/MC 4 R神经元亚群没有变化，但线粒体和MC 4 R蛋白丢失。在患有DIO的两种性别的小鼠中，通过饮食干预重建正常体重，可以恢复Sim 1/MC 4 R神经元中MC 4 R蛋白的丰度和PVN中的神经发生。然而，PVN中非Sim 1/MC 4 R神经元的数量继续减少。DIO后Sim 1/MC 4 R神经元的选择性存活和恢复表明这些神经元是恢复能量稳态和治疗肥胖的优先靶点。
In the melanocortin pathway, melanocortin-4 receptor (MC4R) functions to control energy homeostasis. MC4R is expressed in a sub-population of Sim1 neurons (Sim1/MC4R neurons) and functions in hypothalamic paraventricular nuclei (PVN) to control food intake. Mapping sites of hypothalamic injury in obesity is essential to counteract the disease. In the PVN of male and female mice with diet-induced obesity (DIO) there is neuronal loss. However, the existing subpopulation of PVN Sim1/MC4R neurons is unchanged, but has a loss of mitochondria and MC4R protein. In mice of both sexes with DIO, dietary intervention to re-establish normal weight restores abundance of MC4R protein in Sim1/MC4R neurons and neurogenesis in the PVN. However, the number of non-Sim1/MC4R neurons in the PVN continues to remain decreased. Selective survival and recovery of Sim1/MC4R neurons after DIO suggests these neurons as preferential target to restore energy homeostasis and of therapy against obesity.