A role for VGF in the hypothalamic arcuate and paraventricular nuclei in the control of energy homeostasis

The arcuate nucleus is the main receptive area of the brain for peripheral and central metabolic cues and its integrity is essential for the maintenance of energy homeostasis. In the arcuate nucleus, different neuronal populations process metabolic signals and transmit this information to other nuclei of the hypothalamus by means of neurotransmitters and a combination of neuropeptides whose expression is modulated by the nutritional status. Here we investigated the changes in expression and synthesis of the polypeptide VGF in the arcuate nucleus of rats, in relation to the two main categories of neurons that show colocalization with VGF: the orexigenic NPY-expressing cells and the anorexigenic POMC-expressing cells. The results show that fasting is the most important stimulus for VGF expression, and that the up-regulation of VGF mRNA is restricted to the NPY area of the arcuate nucleus. POMC neurons express VGF under all feeding conditions, but especially in ad libitum-fed and fasted-refed animals. We also show that VGF arcuate neurons project to the pre-autonomic neurons of the paraventricular nucleus of the hypothalamus, providing anatomical evidence suggesting VGF as a central modulator of the autonomic nervous system.