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Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis [Neuroscience]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2021-01-26 , DOI: 10.1073/pnas.2017218118
Jessica Houtz 1 , Guey-Ying Liao 1 , Juan Ji An 1 , Baoji Xu 2
Affiliation  

Mutations in the TrkB neurotrophin receptor lead to profound obesity in humans, and expression of TrkB in the dorsomedial hypothalamus (DMH) is critical for maintaining energy homeostasis. However, the functional implications of TrkB-fexpressing neurons in the DMH (DMHTrkB) on energy expenditure are unclear. Additionally, the neurocircuitry underlying the effect of DMHTrkB neurons on energy homeostasis has not been explored. In this study, we show that activation of DMHTrkB neurons leads to a robust increase in adaptive thermogenesis and energy expenditure without altering heart rate or blood pressure, while silencing DMHTrkB neurons impairs thermogenesis. Furthermore, we reveal neuroanatomically and functionally distinct populations of DMHTrkB neurons that regulate food intake or thermogenesis. Activation of DMHTrkB neurons projecting to the raphe pallidus (RPa) stimulates thermogenesis and increased energy expenditure, whereas DMHTrkB neurons that send collaterals to the paraventricular hypothalamus (PVH) and preoptic area (POA) inhibit feeding. Together, our findings provide evidence that DMHTrkB neuronal activity plays an important role in regulating energy expenditure and delineate distinct neurocircuits that underly the separate effects of DMHTrkB neuronal activity on food intake and thermogenesis.



中文翻译:


下丘脑背内侧表达 TrkB 的离散神经元调节摄食和产热 [神经科学]



TrkB 神经营养蛋白受体的突变会导致人类严重肥胖,而下丘脑背内侧 (DMH) 中 TrkB 的表达对于维持能量稳态至关重要。然而,DMH 中表达 TrkB 的神经元 (DMH TrkB ) 对能量消耗的功能影响尚不清楚。此外,DMH TrkB神经元对能量稳态影响的神经回路尚未被探索。在这项研究中,我们表明,DMH TrkB神经元的激活会导致适应性产热和能量消耗的强劲增加,而不会改变心率或血压,而沉默 DMH TrkB神经元则会损害产热。此外,我们还揭示了调节食物摄入或生热作用的 DMH TrkB神经元在神经解剖学和功能上的不同群体。投射到苍白中缝 (RPa) 的 DMH TrkB神经元的激活会刺激生热作用并增加能量消耗,而将侧支循环发送到室旁下丘脑 (PVH) 和视前区 (POA) 的 DMH TrkB神经元会抑制摄食。总之,我们的研究结果提供了证据,表明 DMH TrkB神经元活动在调节能量消耗中发挥着重要作用,并描绘了不同的神经回路,这些神经回路是 DMH TrkB神经元活动对食物摄入和生热作用的单独影响的基础。

更新日期:2021-01-20
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