School of Psychology, University of New South Wales, Australia; School of Pharmacy, University of Sydney, Australia.
School of Psychology, University of New South Wales, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Australia.
Neuropeptides. 2024 Oct;107:102454. doi: 10.1016/j.npep.2024.102454. Epub 2024 Jul 3.
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.
神经肽 Y（NPY）在控制能量平衡和进食行为方面发挥着关键作用。位于下丘脑弓状核（Arc）的 NPY 神经元对体内平衡信号的反应作用一直是许多研究的焦点，但大多数研究都使用 AgRP 启动子驱动的模型，这些模型不能完全包含 Arc NPY 神经元。为了直接研究表达 NPY 的与表达 AgRP 的 Arc 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，在存在食物和与食物相关的刺激时激活 Arc NPY 或 AgRP 神经元。我们的研究结果表明，化学遗传激活更广泛的 Arc NPY 神经元群体，包括 AgRP 阳性和 AgRP 阴性 NPY 神经元，对进食行为的影响与激活 Arc AgRP 神经元的影响相当。我们的结果表明，这些 Arc 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 神经元中观察到的一致。激活 Arc NPY 神经元可显著增加食物消耗，并影响宏量营养素选择，以优先摄入脂肪。
