Discrete BDNF Neurons in the Paraventricular Hypothalamus Control Feeding and Energy Expenditure.
Discrete BDNF Neurons in the Paraventricular Hypothalamus Control Feeding and Energy Expenditure.
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DOI：
10.1016/j.cmet.2015.05.008
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发表时间：
2015-07-07
期刊：
影响因子：
29
通讯作者：
Xu B
中科院分区：
文献类型：
--
作者：
An JJ;Liao GY;Kinney CE;Sahibzada N;Xu B
脑源性神经营养因子（BDNF）是能量平衡的关键调节因子;然而，其潜在机制仍不清楚。通过分析室旁下丘脑（PVH）中表达BDNF的神经元，我们发现了控制能量平衡的神经回路。PVH中的Bdnf基因主要在以前未定义的神经元中表达，其缺失导致摄食过多，运动活性降低，产热受损和严重肥胖。暴食症和减少运动活动与BDNF缺失在前PVH，而BDNF神经元在内侧和后部PVH驱动产热通过投射到脊髓和形成多突触连接到棕色脂肪组织。此外，BDNF在PVH的表达增加，冷暴露，其消融引起交感节前神经元萎缩。因此，PVH前部的BDNF神经元控制能量摄入和运动活动，而PVH中部和后部的BDNF神经元通过将BDNF释放到脊髓中以促进交感神经流出来促进产热。
Brain-derived neurotrophic factor (BDNF) is a key regulator of energy balance; however, its underlying mechanism remains unknown. By analyzing BDNF-expressing neurons in paraventricular hypothalamus (PVH), we have uncovered neural circuits that control energy balance. The Bdnf gene in the PVH was mostly expressed in previously undefined neurons, and its deletion caused hyperphagia, reduced locomotor activity, impaired thermogenesis, and severe obesity. Hyperphagia and reduced locomotor activity were associated with Bdnf deletion in anterior PVH, whereas BDNF neurons in medial and posterior PVH drive thermogenesis by projecting to spinal cord and forming polysynaptic connections to brown adipose tissues. Furthermore, BDNF expression in the PVH was increased in response to cold exposure, and its ablation caused atrophy of sympathetic preganglionic neurons. Thus, BDNF neurons in anterior PVH control energy intake and locomotor activity, whereas those in medial and posterior PVH promote thermogenesis by releasing BDNF into spinal cord to boost sympathetic outflow.
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