Department of Neurocircuit Development and Function, German Institute of Human Nutrition https://ror.org/05xdczy51, Nuthetal, Germany.
NeuroCure Cluster of Excellence, Charité-Universitätsmedizin, Berlin, Germany.
Life Sci Alliance. 2024 Aug 6;7(10). doi: 10.26508/lsa.202402754. Print 2024 Oct.
The brain controls energy homeostasis by regulating food intake through signaling within the melanocortin system. Whilst we understand the role of the hypothalamus within this system, how extra-hypothalamic brain regions are involved in controlling energy balance remains unclear. Here we show that the melanocortin 3 receptor (MC3R) is expressed in the paraventricular nucleus of the thalamus (PVT). We tested whether fasting would change the activity of MC3R neurons in this region by assessing the levels of c-Fos and pCREB as neuronal activity markers. We determined that overnight fasting causes a significant reduction in pCREB levels within PVT-MC3R neurons. We then questioned whether perturbation of MC3R signaling, during fasting, would result in altered refeeding. Using chemogenetic approaches, we show that modulation of MC3R activity, during the fasting period, does not impact body weight regain or total food intake in the refeeding period. However, we did observe significant differences in the pattern of feeding-related behavior. These findings suggest that the PVT is a region where MC3R neurons respond to energy deprivation and modulate refeeding behavior.
大脑通过黑皮质素系统内的信号调节食物摄入来控制能量稳态。虽然我们了解了下丘脑在该系统中的作用，但额外的下丘脑外脑区如何参与控制能量平衡仍不清楚。在这里，我们表明黑皮质素 3 受体（MC3R）在丘脑室旁核（PVT）中表达。我们通过评估作为神经元活动标记物的 c-Fos 和 pCREB 的水平来测试禁食是否会改变该区域 MC3R 神经元的活性。我们确定隔夜禁食会导致 PVT-MC3R 神经元内 pCREB 水平的显著降低。然后，我们询问禁食期间 MC3R 信号的干扰是否会导致再喂养的改变。使用化学遗传方法，我们表明禁食期间 MC3R 活性的调节不会影响再喂养期间的体重恢复或总食物摄入量。然而，我们确实观察到与进食相关的行为模式存在显著差异。这些发现表明，PVT 是一个 MC3R 神经元对能量剥夺作出反应并调节再喂养行为的区域。
