Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding.,Cell Metabolism

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Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding.
Cell Metabolism ( IF 27.7 ) Pub Date : 2020-01-16 , DOI: 10.1016/j.cmet.2019.12.012
Wenwen Cheng ₁ , Ian Gonzalez ₂ , Warren Pan ₃ , Anthony H Tsang ₄ , Jessica Adams ₅ , Ermelinda Ndoka ₁ , Desiree Gordian ₁ , Basma Khoury ₆ , Karen Roelofs ₆ , Simon S Evers ₆ , Andrew MacKinnon ₁ , Shuangcheng Wu ₇ , Henriette Frikke-Schmidt ₆ , Jonathan N Flak ₁ , James L Trevaskis ₈ , Christopher J Rhodes ₈ , So-Ichiro Fukada ₉ , Randy J Seeley ₆ , Darleen A Sandoval ₁₀ , David P Olson ₂ , Clemence Blouet ₄ , Martin G Myers ₁₁

Affiliation

Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48105, USA.
Division of Endocrinology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48105, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA.
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48105, USA; Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48105, USA.
MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK.
Division of Endocrinology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48105, USA.
Department of Surgery, University of Michigan, Ann Arbor, MI 48105, USA.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA.
Cardiovascular, Renal and Metabolic Diseases, AstraZenica LLC, Gaithersburg, MD 20878, USA.
Laboratory of Molecular and Cellular Physiology, Osaka University, Osaka 565-0871, Japan.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA; Department of Surgery, University of Michigan, Ann Arbor, MI 48105, USA.
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48105, USA; Division of Endocrinology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48105, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA; Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48105, USA.

To understand hindbrain pathways involved in the control of food intake, we examined roles for calcitonin receptor (CALCR)-containing neurons in the NTS. Ablation of NTS Calcr abrogated the long-term suppression of food intake, but not aversive responses, by CALCR agonists. Similarly, activating CalcrNTS neurons decreased food intake and body weight but (unlike neighboring CckNTS cells) failed to promote aversion, revealing that CalcrNTS neurons mediate a non-aversive suppression of food intake. While both CalcrNTS and CckNTS neurons decreased feeding via projections to the PBN, CckNTS cells activated aversive CGRPPBN cells while CalcrNTS cells activated distinct non-CGRP PBN cells. Hence, CalcrNTS cells suppress feeding via non-aversive, non-CGRP PBN targets. Additionally, silencing CalcrNTS cells blunted food intake suppression by gut peptides and nutrients, increasing food intake and promoting obesity. Hence, CalcrNTS neurons define a hindbrain system that participates in physiological energy balance and suppresses food intake without activating aversive systems.

中文翻译：

小鼠孤束核中的降钙素受体神经元通过非厌恶性抑制进食控制能量平衡。

为了了解参与控制食物摄入的后脑通路，我们检查了 NTS 中含有降钙素受体 (CALCR) 的神经元的作用。NTS Calcr 的消融消除了 CALCR 激动剂对食物摄入的长期抑制，但不是厌恶反应。同样，激活 CalcrNTS 神经元可减少食物摄入和体重，但（与邻近的 CckNTS 细胞不同）未能促进厌恶，这表明 CalcrNTS 神经元介导了对食物摄入的非厌恶抑制。虽然 CalcrNTS 和 CckNTS 神经元都通过投射到 PBN 的方式减少了进食，但 CckNTS 细胞激活了厌恶的 CGRPPBN 细胞，而 CalcrNTS 细胞激活了不同的非 CGRP PBN 细胞。因此，CalcrNTS 细胞通过非厌恶性、非 CGRP PBN 目标抑制进食。此外，使CalcrNTS细胞沉默减弱了肠道肽和营养物质对食物摄入的抑制，增加了食物摄入并促进了肥胖。因此，CalcrNTS 神经元定义了一个后脑系统，该系统参与生理能量平衡并在不激活厌恶系统的情况下抑制食物摄入。

更新日期：2020-01-17

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