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化学遗传激活内源性血管加压素通过中枢 nesfatin-1/NucB2 通路发挥厌食作用。

Chemogenetic activation of endogenous arginine vasopressin exerts anorexigenic effects via central nesfatin-1/NucB2 pathway.

机构信息

Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.

Second Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.

出版信息

J Physiol Sci. 2021 Jun 16;71(1):18. doi: 10.1186/s12576-021-00802-4.

DOI:10.1186/s12576-021-00802-4
PMID:34134629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10717637/
Abstract

We examined whether the chemogenetic activation of endogenous arginine vasopressin (AVP) affects central nesfatin-1/NucB2 neurons, using a transgenic rat line that was previously generated. Saline (1 mL/kg) or clozapine-N-oxide (CNO, 1 mg/mL/kg), an agonist for hM3Dq, was subcutaneously administered in adult male AVP-hM3Dq-mCherry transgenic rats (300-370 g). Food and water intake were significantly suppressed after subcutaneous (s.c.) injection of CNO, with aberrant circadian rhythmicity. The percentages of Fos expression in nesfatin-1/NucB2-immunoreactive neurons were significantly increased in the hypothalamus and brainstem at 120 min after s.c. injection of CNO. Suppressed food intake that was induced by chemogenetic activation of endogenous AVP was ablated after intracerebroventricularly administered nesfatin-1/NucB2-neutralizing antibody in comparison with vehicle, without any alteration of water intake nor circadian rhythmicity. These results suggest that chemogenetic activation of endogenous AVP affects, at least in part, central nesfatin-1/NucB2 neurons and may exert anorexigenic effects in the transgenic rats.

摘要

我们使用之前生成的转基因大鼠品系，研究了内源性精氨酸加压素（AVP）的化学遗传激活是否会影响中枢 nesfatin-1/NucB2 神经元。在成年雄性 AVP-hM3Dq-mCherry 转基因大鼠（300-370g）中，皮下给予生理盐水（1ml/kg）或 clozapine-N-oxide（CNO，1mg/ml/kg），这是 hM3Dq 的激动剂。皮下注射 CNO 后，摄食量和饮水量明显减少，并出现异常的昼夜节律。在 CNO 皮下注射 120 分钟后，下丘脑和脑干中 nesfatin-1/NucB2 免疫反应性神经元中的 Fos 表达百分比显著增加。与载体相比，脑室注射 nesfatin-1/NucB2 中和抗体可消除化学遗传激活内源性 AVP 诱导的摄食抑制，而不改变水的摄入或昼夜节律。这些结果表明，内源性 AVP 的化学遗传激活至少部分影响中枢 nesfatin-1/NucB2 神经元，并可能在转基因大鼠中发挥厌食作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8713/10717637/27a286078450/12576_2021_802_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8713/10717637/e6d7d002d286/12576_2021_802_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8713/10717637/b63f299cc3a4/12576_2021_802_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8713/10717637/7ad895a1beff/12576_2021_802_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8713/10717637/9b79982990b4/12576_2021_802_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8713/10717637/27a286078450/12576_2021_802_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8713/10717637/e6d7d002d286/12576_2021_802_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8713/10717637/b63f299cc3a4/12576_2021_802_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8713/10717637/7ad895a1beff/12576_2021_802_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8713/10717637/9b79982990b4/12576_2021_802_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8713/10717637/27a286078450/12576_2021_802_Fig5_HTML.jpg

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引用本文的文献

[1]
Molecular Interaction Between Vasopressin and Insulin in Regulation of Metabolism: Impact on Cardiovascular and Metabolic Diseases.

Int J Mol Sci. 2024-12-11

[2]
Vasopressin and Breathing: Review of Evidence for Respiratory Effects of the Antidiuretic Hormone.

Front Physiol. 2021-10-26

本文引用的文献

[1]
Arginine vasopressin: Direct and indirect action on metabolism.

Peptides. 2021-8

[2]
Nucleobindin 2/nesfatin-1 expression and colocalisation with neuropeptide Y and cocaine- and amphetamine-regulated transcript in the human brainstem.

J Neuroendocrinol. 2020-9

[3]
Serotonergic Plasticity in the Dorsal Raphe Nucleus Characterizes Susceptibility and Resilience to Anhedonia.

J Neurosci. 2019-12-2

[4]
Chemogenetic manipulation of parasympathetic neurons (DMV) regulates feeding behavior and energy metabolism.

Neurosci Lett. 2019-8-27

[5]
The circadian regulation of food intake.

Nat Rev Endocrinol. 2019-7

[6]
The Network Mechanism of the Central Circadian Pacemaker of the SCN: Do AVP Neurons Play a More Critical Role Than Expected?

Front Neurosci. 2019-2-25

[7]
Activation of endogenous arginine vasopressin neurons inhibit food intake: by using a novel transgenic rat line with DREADDs system.

Sci Rep. 2017-11-16

[8]
Nesfatin-1 regulates the lateral hypothalamic area melanin-concentrating hormone-responsive gastric distension-sensitive neurons and gastric function via arcuate nucleus innervation.

Metabolism. 2017-2

[9]
Vagal neurocircuitry and its influence on gastric motility.

Nat Rev Gastroenterol Hepatol. 2016-7

[10]
Nesfatin-1 signaling in the basom edial amygdala modulates the gastric distension-sensitive neurons discharge and decreases gastric motility via melanocortin 3/4 receptors and modified by the arcuate nucleus.

Eur J Pharmacol. 2015-10-5

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