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多个 NTS 神经元群体累积抑制摄食。

Multiple NTS neuron populations cumulatively suppress food intake.

机构信息

Department of Internal Medicine, University of Michigan, Ann Arbor, United States.

Department of Surgery, University of Michigan, Ann Arbor, United States.

出版信息

Elife. 2023 Dec 7;12:e85640. doi: 10.7554/eLife.85640.


DOI:10.7554/eLife.85640
PMID:38059498
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10781422/
Abstract

Several discrete groups of feeding-regulated neurons in the nucleus of the solitary tract (; NTS) suppress food intake, including avoidance-promoting neurons that express (NTS cells) and distinct - and -expressing neurons (NTS and NTS cells, respectively) that suppress food intake without promoting avoidance. To test potential synergies among these cell groups, we manipulated multiple NTS cell populations simultaneously. We found that activating multiple sets of NTS neurons (e.g. NTS plus NTS [NTS], or NTS plus NTS [NTS]) suppressed feeding more robustly than activating single populations. While activating groups of cells that include NTS neurons promoted conditioned taste avoidance (CTA), NTS activation produced no CTA despite abrogating feeding. Thus, the ability to promote CTA formation represents a dominant effect but activating multiple non-aversive populations augments the suppression of food intake without provoking avoidance. Furthermore, silencing multiple NTS neuron groups augmented food intake and body weight to a greater extent than silencing single populations, consistent with the notion that each of these NTS neuron populations plays crucial and cumulative roles in the control of energy balance. We found that silencing NTS neurons failed to blunt the weight-loss response to vertical sleeve gastrectomy (VSG) and that feeding activated many non-NTS neurons, however, suggesting that as-yet undefined NTS cell types must make additional contributions to the restraint of feeding.

摘要

孤束核(NTS)中的几个离散的进食调节神经元群抑制摄食,包括促进回避的神经元(表达神经降压素的 NTS 细胞)和表达神经降压素受体 1 和神经肽 Y 的神经元(分别为 NTS 和 NTS 细胞,它们抑制摄食而不促进回避)。为了测试这些细胞群之间的潜在协同作用,我们同时操纵多个 NTS 细胞群体。我们发现,激活多个 NTS 神经元群(例如 NTS 加 NTS[NTS],或 NTS 加 NTS[NTS])比激活单个群体更能有效地抑制摄食。虽然激活包括 NTS 神经元的细胞群会促进条件性味觉回避(CTA),但 NTS 的激活不会引起 CTA,尽管它会抑制摄食。因此,促进 CTA 形成的能力代表了一种主要效应,但激活多个非厌恶性群体在不引起回避的情况下增强了对食物摄入的抑制。此外,沉默多个 NTS 神经元群体比沉默单个群体更能显著增加食物摄入和体重,这与以下观点一致,即这些 NTS 神经元群体中的每一个都在能量平衡的控制中发挥着关键和累积的作用。我们发现,沉默 NTS 神经元并不能削弱垂直袖状胃切除术(VSG)引起的体重减轻反应,而且进食激活了许多非 NTS 神经元,这表明尚未定义的 NTS 细胞类型必须对摄食的抑制做出额外的贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/73c1afa98370/elife-85640-fig6-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/6bd3b82afb3f/elife-85640-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/bef9d3ba3deb/elife-85640-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/f98bf5bf089a/elife-85640-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/b86332790483/elife-85640-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/f850637fb9f9/elife-85640-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/bd5b59557a8c/elife-85640-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/80623e565881/elife-85640-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/00215c8b32bf/elife-85640-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/9b22b6686bba/elife-85640-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/ef582c06b1b9/elife-85640-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/51b6c2bcc98a/elife-85640-fig6-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/73c1afa98370/elife-85640-fig6-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/6bd3b82afb3f/elife-85640-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/bef9d3ba3deb/elife-85640-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/f98bf5bf089a/elife-85640-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/b86332790483/elife-85640-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/f850637fb9f9/elife-85640-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/bd5b59557a8c/elife-85640-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/80623e565881/elife-85640-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/00215c8b32bf/elife-85640-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/9b22b6686bba/elife-85640-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/ef582c06b1b9/elife-85640-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/51b6c2bcc98a/elife-85640-fig6-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e07/10781422/73c1afa98370/elife-85640-fig6-figsupp3.jpg

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本文引用的文献

[1]
Hindbrain circuits in the control of eating behaviour and energy balance.

Nat Metab. 2022-7

[2]
NTS Prlh overcomes orexigenic stimuli and ameliorates dietary and genetic forms of obesity.

Nat Commun. 2021-8-30

[3]
Examining the Rates of Obesity and Bariatric Surgery in the United States.

Obes Surg. 2021-11

[4]
Single-Cell Mapping of GLP-1 and GIP Receptor Expression in the Dorsal Vagal Complex.

Diabetes. 2021-9

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A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing.

Mol Metab. 2021-11

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Nat Metab. 2021-4

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Neuron. 2021-2-3

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A Leptin-Mediated Neural Mechanism Linking Breathing to Metabolism.

Cell Rep. 2020-11-10

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Nutrient sensing in the nucleus of the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons.

Mol Metab. 2020-12

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Leptin receptor-expressing nucleus tractus solitarius neurons suppress food intake independently of GLP1 in mice.

JCI Insight. 2020-4-9

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