Heparin Increases Food Intake through AgRP Neurons.

Heparin Increases Food Intake through AgRP Neurons.
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DOI:
10.1016/j.celrep.2017.08.049
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发表时间:
2017-09-05
期刊:
影响因子:
8.8
通讯作者:
Shu G
Shu G
中科院分区:
生物学1区
文献类型:
--
作者:
Zhu C;Xu P;He Y;Yuan Y;Wang T;Cai X;Yu L;Yang L;Wu J;Wang L;Zhu X;Wang S;Gao P;Xi Q;Zhang Y;Xu Y;Jiang Q;Shu G

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虽然广泛使用的抗凝药物肝素已被证明有许多其他的生物功能,独立于其抗凝作用,其对能量稳态的影响是未知的。在这里,我们证明了肝素水平与营养状态呈负相关,肝素治疗增加了食物摄入量和体重增加。通过使用电生理学、药理学、分子生物学和化学遗传学方法,我们提供了肝素通过刺激AgRP神经元和增加AgRP释放来增加食物摄入的证据。我们的研究结果支持一种模型,即肝素竞争与胰岛素的胰岛素受体结合的AgRP神经元,并通过这样做,它抑制FoxO1活性,促进AgRP的释放和喂养。肝素可能是一个潜在的药物靶点,用于食物摄入调节和体重控制。Zhu等人证明,肝素与胰岛素竞争结合AgRP神经元上的胰岛素受体,并通过这样做抑制FoxO1活性以促进AgRP释放和进食。肝素被确定为调节食物摄入和控制体重的潜在药物靶点。
Although the widely used anticoagulant drug heparin has been shown to have many other biological functions independent of its anticoagulant role, its effects on energy homeostasis are unknown. Here, we demonstrate that heparin level is negatively associated with nutritional states and that heparin treatment increases food intake and body weight gain. By using electrophysiological, pharmacological, molecular biological, and chemogenetic approaches, we provide evidence that heparin increases food intake by stimulating AgRP neurons and increasing AgRP release. Our results support a model whereby heparin competes with insulin for insulin receptor binding on AgRP neurons, and by doing so it inhibits FoxO1 activity to promote AgRP release and feeding. Heparin may be a potential drug target for food intake regulation and body weight control. Zhu et al. demonstrate that heparin competes with insulin for insulin receptor binding on AgRP neurons, and by doing so it inhibits FoxO1 activity to promote AgRP release and feeding. Heparin is identified as a potential drug target for food intake regulation and body weight control.
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