Chemogenetic activation ofarcuate nucleus NPY and NPY/AgRP neurons increases feeding behaviour in mice

IF 2.5 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Neda Rafiei , Caitlin S. Mitchell , Caitlin R. Tedesco , Jessica Chen , Eun A. Choi , Stephanie Roughley , Philip Jean-Richard-dit-Bressel , Natasha N. Kumar , Gavan P. McNally , Herbert Herzog , Denovan P. Begg
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引用次数: 0

Abstract

Neuropeptide Y (NPY) plays a crucial role in controlling energy homeostasis and feeding behaviour. The role of NPY neurons located in the arcuate nucleus of the hypothalamus (Arc) in responding to homeostatic signals has been the focus of much investigation, but most studies have used AgRP promoter-driven models, which do not fully encompass Arc NPY neurons. To directly investigate NPY-expressing versus AgRP-expressing Arc neurons function, we utilised chemogenetic techniques in NPY-Cre and AgRP-Cre animals to activate Arc NPY or AgRP neurons in the presence of food and food-related stimuli. Our findings suggest that chemogenetic activation of the broader population of Arc NPY neurons, including AgRP-positive and AgRP-negative NPY neurons, has equivalent effects on feeding behaviour as activation of Arc AgRP neurons. Our results demonstrate that these Arc NPY neurons respond specifically to caloric signals and do not respond to non-caloric signals, in line with what has been observed in AgRP neurons. Activating Arc NPY neurons significantly increases food consumption and influences macronutrient selection to prefer fat intake.

用化学方法激活阿尔卡特核NPY和NPY/AgRP神经元可增加小鼠的摄食行为
神经肽 Y(NPY)在控制能量平衡和摄食行为方面起着至关重要的作用。位于下丘脑弓状核(Arc)的 NPY 神经元在响应平衡信号中的作用一直是研究的重点,但大多数研究都使用了 AgRP 启动子驱动的模型,这并不能完全涵盖 Arc NPY 神经元。为了直接研究表达 NPY 与表达 AgRP 的弧神经元的功能,我们在 NPY-Cre 和 AgRP-Cre 动物中利用化学遗传技术,在食物和食物相关刺激下激活弧 NPY 或 AgRP 神经元。我们的研究结果表明,化学基因激活更广泛的弧 NPY 神经元群(包括 AgRP 阳性和 AgRP 阴性 NPY 神经元)对摄食行为的影响与激活弧 AgRP 神经元的影响相当。我们的研究结果表明,这些弧 NPY 神经元对热量信号有特异性反应,而对非热量信号没有反应,这与在 AgRP 神经元中观察到的结果一致。激活弧 NPY 神经元可显著增加食物消耗量,并影响宏量营养素的选择,使其更倾向于脂肪摄入。
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来源期刊
Neuropeptides
Neuropeptides 医学-内分泌学与代谢
CiteScore
5.40
自引率
6.90%
发文量
55
审稿时长
>12 weeks
期刊介绍: The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.
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