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

Abstract

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.

Mediators of Amylin Action in Metabolic Control

“…In other words, depletion of the CTR in the VMN rendered a more DIO-like phenotype in the DR rats and led to increased adiposity [105]. Other studies lend support to the important role of CTR signaling on leptin responsive hypothalamic neurons for metabolic control [167,168]. The discovery that leptin receptor deficient db/db mice have less CTR expression in the AP adds to these findings [95], but they cannot easily be translated to humans because primary leptin receptor deficiency is not the cause of common obesity.…”

The role of ghrelin in normal and pathological conditions

“…Эксперименты на мышах с блокированием как самого Г [13,14], так и его рецептора [15] показали, что отсутствие влияния Г может защитить от раннего ожирения. Рецептор Г ранее назывался рецептор стимуляции секреции ГР.…”