A Small Potassium Current in AgRP/NPY Neurons Regulates Feeding Behavior and Energy Metabolism.
A Small Potassium Current in AgRP/NPY Neurons Regulates Feeding Behavior and Energy Metabolism.
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DOI：
10.1016/j.celrep.2016.10.044
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发表时间：
2016-11-08
期刊：
影响因子：
8.8
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
He Y;Shu G;Yang Y;Xu P;Xia Y;Wang C;Saito K;Hinton A Jr;Yan X;Liu C;Wu Q;Tong Q;Xu Y
共同表达刺鼠相关肽（AgRP）和神经肽Y（NPY）的神经元对于正常的摄食行为是必不可少的。AgRP/NPY神经元的放电活动受能量状态的动态调节，并协调适当的摄食行为以满足营养需求。然而，在进食至禁食过渡期间调节AgRP/NPY神经活动的内在机制尚未完全了解。我们发现，在饱食小鼠的AgRP/NPY神经元表达高水平的小电导钙激活钾通道3（SK 3），并抑制SK 3介导的钾电流;另一方面，食物剥夺抑制SK 3在AgRP/NPY神经元的表达，减少SK 3介导的电流有助于禁食诱导激活这些神经元。SK 3基因突变，特别是在AgRP/NPY神经元导致增加的敏感性，饮食诱导的肥胖，与慢性暴食症和减少能量消耗。我们的研究结果确定SK 3作为一个关键的内在介质，协调营养状况与AgRP/NPY神经活动和动物的摄食行为和能量代谢。AgRP/NPY神经元的放电活动对于能量稳态是必不可少的。Heet al.证明SK 3介导的电流抑制饱足小鼠中的AgRP/NPY神经元，并且降低的SK 3表达有助于禁食诱导的这些神经元的激活。因此，动态SK 3功能协调营养状态与AgRP/NPY神经活动和动物的能量平衡。
Neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons are dynamically regulated by energy status and coordinate appropriate feeding behavior to meet nutritional demands. However, intrinsic mechanisms that regulate AgRP/NPY neural activities during the fed-to-fasted transition are not fully understood. We found that AgRP/NPY neurons in satiated mice express high levels of the small-conductance calcium-activated potassium channel 3 (SK3) and are inhibited by SK3-mediated potassium currents; on the other hand, food deprivation suppresses SK3 expression in AgRP/NPY neurons, and the decreased SK3-mediated currents contribute to fasting-induced activation of these neurons. Genetic mutation of SK3 specifically in AgRP/NPY neurons leads to increased sensitivity to diet-induced obesity, associated with chronic hyperphagia and decreased energy expenditure. Our results identify SK3 as a key intrinsic mediator that coordinates nutritional status with AgRP/NPY neural activities and animals’ feeding behavior and energy metabolism. Firing activities of AgRP/NPY neurons are essential for energy homeostasis. Heet al. demonstrate that SK3-mediated currents inhibit AgRP/NPY neurons in satiated mice and decreased SK3 expression contributes to fasting-induced activation of these neurons. Thus, dynamic SK3 functions coordinate nutritional status with AgRP/NPY neural activities and animals’ energy balance.
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影响因子：
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