Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Division of Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
Endocrinology. 2021 Jun 1;162(6). doi: 10.1210/endocr/bqab072.
The paraventricular nucleus of the hypothalamus (PVH) is a heterogeneous collection of neurons that play important roles in modulating feeding and energy expenditure. Abnormal development or ablation of the PVH results in hyperphagic obesity and defects in energy expenditure whereas selective activation of defined PVH neuronal populations can suppress feeding and may promote energy expenditure. Here, we characterize the contribution of calcitonin receptor-expressing PVH neurons (CalcRPVH) to energy balance control. We used Cre-dependent viral tools delivered stereotaxically to the PVH of CalcR2Acre mice to activate, silence, and trace CalcRPVH neurons and determine their contribution to body weight regulation. Immunohistochemistry of fluorescently-labeled CalcRPVH neurons demonstrates that CalcRPVH neurons are largely distinct from several PVH neuronal populations involved in energy homeostasis; these neurons project to regions of the hindbrain that are implicated in energy balance control, including the nucleus of the solitary tract and the parabrachial nucleus. Acute activation of CalcRPVH neurons suppresses feeding without appreciably augmenting energy expenditure, whereas their silencing leads to obesity that may be due in part due to loss of PVH melanocortin-4 receptor signaling. These data show that CalcRPVH neurons are an essential component of energy balance neurocircuitry and their function is important for body weight maintenance. A thorough understanding of the mechanisms by which CalcRPVH neurons modulate energy balance might identify novel therapeutic targets for the treatment and prevention of obesity.
下丘脑室旁核（PVH）是神经元的异质集合，在调节摄食和能量消耗方面发挥着重要作用。PVH 的异常发育或消融会导致多食性肥胖和能量消耗缺陷，而选择性激活特定的 PVH 神经元群可以抑制摄食，并可能促进能量消耗。在这里，我们描述了降钙素受体表达的 PVH 神经元（CalcRPVH）对能量平衡控制的贡献。我们使用 Cre 依赖性病毒工具通过立体定向递送至 CalcR2Acre 小鼠的 PVH 中，以激活、沉默和追踪 CalcRPVH 神经元，并确定它们对体重调节的贡献。荧光标记的 CalcRPVH 神经元的免疫组织化学显示，CalcRPVH 神经元在很大程度上与参与能量稳态的几个 PVH 神经元群不同；这些神经元投射到涉及能量平衡控制的后脑区域，包括孤束核和臂旁核。CalcRPVH 神经元的急性激活抑制摄食而不会明显增加能量消耗，而其沉默导致肥胖，部分原因可能是由于 PVH 黑皮质素-4 受体信号的丧失。这些数据表明，CalcRPVH 神经元是能量平衡神经回路的重要组成部分，它们的功能对于维持体重很重要。深入了解 CalcRPVH 神经元调节能量平衡的机制可能会为肥胖的治疗和预防确定新的治疗靶点。
