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下丘脑腹内侧核中Nesfatin-1对胃功能的抑制作用及其受伏隔核的调节

The Inhibitory Effects of Nesfatin-1 in Ventromedial Hypothalamus on Gastric Function and Its Regulation by Nucleus Accumbens.

作者信息

Gao Shengli, Guo Feifei, Sun Xiangrong, Zhang Nana, Gong Yanling, Xu Luo

机构信息

Department of Pathophysiology, School of Basic Medicine, Qingdao University Qingdao, China.

Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University Qingdao, China.

出版信息

Front Physiol. 2017 Jan 5;7:634. doi: 10.3389/fphys.2016.00634. eCollection 2016.

DOI:10.3389/fphys.2016.00634
PMID:28105016
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5213809/
Abstract

The aim of this study was to investigate the effect of nesfatin-1 signaling in the ventromedial hypothalamus (VMH) on gastric functions, as well as the regulation of these effects by nucleus accumbens (NAc) projections to VMH. The expression of c-fos in nesfatinergic VMH neurons induced by gastric distension (GD) was measured using the double fluoro-immunohistochemical staining. The firing rates of neurons were monitored with single-unit extracellular electric discharge recording. The projection of nesfatinergic neurons from NAc to VMH was observed by fluorogold retrograde tracer combined with fluoro-immunohistochemical staining. The effect of nesfatin-1 in VMH or electric stimulation in NAc on gastric function was studied by measuring food intake, gastric acid output, gastric motility, and gastric emptying, and the ability of the melanocortin-3/4 receptor antagonist SHU9119 or the anti-nesfatin-1 antibody to block nesfatin-1 in the VMH was assessed. Expression of c-fos was observed in VMH nesfatinergic neurons following GD in rats. Further, nesfatin-1 delivery to single GD-responsive neurons changed the firing rates of these neurons in the VMH. In awake, behaving rats, intra-VMH administration of nesfatin-1 inhibited food intake, gastric acid output, gastric motility, and gastric emptying. These effects were abolished by SHU9119. Fluorogold retrograde tracing showed nesfatinergic neural projection from the NAc to the VMH. Electrical stimulation of NAc modified the firing rates of the VMH neurons and inhibited food intake and gastric functions. The pretreatment with an anti-nesfatin-1 antibody in the VMH reversed the effects of NAc electrical stimulation on the VMH neuronal firing rates and gastric function. Nesfatin-1 in the VMH inhibited food intake, gastric acid output, gastric motility, and gastric emptying. A nesfatinergic pathway between NAc and VMH transmitted metabolism-regulating signals.

摘要

本研究旨在探讨腹内侧下丘脑（VMH）中nesfatin-1信号对胃功能的影响，以及伏隔核（NAc）向VMH投射对这些影响的调节作用。采用双荧光免疫组织化学染色法检测胃扩张（GD）诱导的nesfatin能VMH神经元中c-fos的表达。通过单单位细胞外放电记录监测神经元的放电频率。采用荧光金逆行示踪剂结合荧光免疫组织化学染色观察NAc中nesfatin能神经元向VMH的投射。通过测量食物摄入量、胃酸分泌量、胃动力和胃排空，研究VMH中nesfatin-1或NAc电刺激对胃功能的影响，并评估促黑素皮质素-3/4受体拮抗剂SHU9119或抗nesfatin-1抗体阻断VMH中nesfatin-1的能力。在大鼠GD后，观察到VMH nesfatin能神经元中c-fos表达。此外，将nesfatin-1传递至单个GD反应性神经元可改变VMH中这些神经元的放电频率。在清醒、行为活跃的大鼠中，VMH内注射nesfatin-1可抑制食物摄入、胃酸分泌量、胃动力和胃排空。这些作用被SHU9119消除。荧光金逆行追踪显示有从NAc到VMH的nesfatin能神经投射。电刺激NAc可改变VMH神经元的放电频率，并抑制食物摄入和胃功能。VMH中预先用抗nesfatin-1抗体处理可逆转NAc电刺激对VMH神经元放电频率和胃功能的影响。VMH中的nesfatin-1抑制食物摄入、胃酸分泌量、胃动力和胃排空。NAc和VMH之间的nesfatin能通路传递代谢调节信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd7/5213809/353cd5cc5b23/fphys-07-00634-g0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd7/5213809/7c743a135611/fphys-07-00634-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd7/5213809/dfc41121a6ce/fphys-07-00634-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd7/5213809/353cd5cc5b23/fphys-07-00634-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd7/5213809/a9aa5d7072ac/fphys-07-00634-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd7/5213809/55a2b4c90ef4/fphys-07-00634-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd7/5213809/9388951200dc/fphys-07-00634-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd7/5213809/5e0b0ced7ed1/fphys-07-00634-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd7/5213809/7c743a135611/fphys-07-00634-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd7/5213809/dfc41121a6ce/fphys-07-00634-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afd7/5213809/353cd5cc5b23/fphys-07-00634-g0007.jpg

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本文引用的文献

[1]
Direct hypothalamic and indirect trans-pallidal, trans-thalamic, or trans-septal control of accumbens signaling and their roles in food intake.

Front Syst Neurosci. 2015-2-13

[2]
Nesfatin-1 suppresses gastric contractions and inhibits interdigestive migrating contractions in conscious dogs.

Dig Dis Sci. 2015-6

[3]
The effects of nesfatin-1 in the paraventricular nucleus on gastric motility and its potential regulation by the lateral hypothalamic area in rats.

J Neurochem. 2015-2

[4]
Acute oral metformin enhances satiation and activates brainstem nesfatinergic neurons.

Obesity (Silver Spring). 2014-12

[5]
Effects of exogenous nesfatin-1 on gastric distention-sensitive neurons in the central nucleus of the amygdala and gastric motility in rats.

Neurosci Lett. 2014-10-17

[6]
Expression of gastrointestinal nesfatin-1 and gastric emptying in ventromedial hypothalamic nucleus- and ventrolateral hypothalamic nucleus-lesioned rats.

World J Gastroenterol. 2014-6-14

[7]
Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.

Lancet. 2014-5-29

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Opioid hedonic hotspot in nucleus accumbens shell: mu, delta, and kappa maps for enhancement of sweetness "liking" and "wanting".

J Neurosci. 2014-3-19

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Central nesfatin-1 influences the excitability of ghrelin-responsive gastric distension neurons in the arcuate nucleus and reduces gastric motility in rats.

Eur J Neurosci. 2013-9-23

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Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks.

J Clin Invest. 2013-11-15

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