Paraventricular Calcitonin Receptor Expressing Neurons Modulate Energy Homeostasis in Male Mice.

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 (CalcR PVH) to energy balance control. We used Cre-dependent viral tools delivered stereotaxically to the PVH of CalcR 2Acre mice to activate, silence and trace CalcR PVH neurons and determine their contribution to body weight regulation. Immunohistochemistry of fluorescently-labelled CalcR PVH neurons demonstrates that CalcR PVH 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 CalcR PVH 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 (MC4R) signaling. These data show that CalcR PVH 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 CalcR PVH neurons modulate energy balance might identify novel therapeutic targets for the treatment and prevention of obesity.