Izawa Shuntaro, Yoneshiro Takeshi, Kondoh Kunio, Nakagiri Shohei, Okamatsu-Ogura Yuko, Terao Akira, Minokoshi Yasuhiko, Yamanaka Akihiro, Kimura Kazuhiro
Laboratory of Biochemistry, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan.
Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, 464-8601, Japan.
J Physiol. 2022 Feb;600(4):815-827. doi: 10.1113/JP281241. Epub 2021 May 13.
Melanin-concentrating hormone (MCH) neuron-ablated mice exhibit increased energy expenditure and reduced fat weight. Increased brown adipose tissue (BAT) activity and locomotor activity-independent energy expenditure contributed to body weight reduction in MCH neuron-ablated mice. MCH neurons send inhibitory input to the medullary raphe nucleus to modulate BAT activity.
Hypothalamic melanin-concentrating hormone (MCH) peptide robustly affects energy homeostasis. However, it is unclear whether and how MCH-producing neurons, which contain and release a variety of neuropeptides/transmitters, regulate energy expenditure in the central nervous system and peripheral tissues. We thus examined the regulation of energy expenditure by MCH neurons, focusing on interscapular brown adipose tissue (BAT) activity. MCH neuron-ablated mice exhibited reduced body weight, increased oxygen consumption, and increased BAT activity, which improved locomotor activity-independent energy expenditure. Trans-neuronal retrograde tracing with the recombinant pseudorabies virus revealed that MCH neurons innervate BAT via the sympathetic premotor region in the medullary raphe nucleus (MRN). MRN neurons were activated by MCH neuron ablation. Therefore, endogenous MCH neuron activity negatively modulates energy expenditure via BAT inhibition. MRN neurons might receive inhibitory input from MCH neurons to suppress BAT activity.
黑色素聚集激素（MCH）神经元消融的小鼠表现出能量消耗增加和脂肪重量减轻。褐色脂肪组织（BAT）活性增加以及与运动活动无关的能量消耗导致MCH神经元消融小鼠体重减轻。MCH神经元向延髓中缝核发送抑制性输入以调节BAT活性。
下丘脑黑色素聚集激素（MCH）肽强烈影响能量稳态。然而，尚不清楚含有并释放多种神经肽/递质的产生MCH的神经元是否以及如何在中枢神经系统和外周组织中调节能量消耗。因此，我们研究了MCH神经元对能量消耗的调节，重点关注肩胛间褐色脂肪组织（BAT）的活性。MCH神经元消融的小鼠体重减轻、耗氧量增加且BAT活性增加，这改善了与运动活动无关的能量消耗。用重组伪狂犬病病毒进行的跨神经元逆行示踪显示，MCH神经元通过延髓中缝核（MRN）中的交感运动前区支配BAT。MRN神经元因MCH神经元消融而被激活。因此，内源性MCH神经元活性通过抑制BAT对能量消耗产生负调节作用。MRN神经元可能接收来自MCH神经元的抑制性输入以抑制BAT活性。
