Neuropeptide Y and α-melanocyte-stimulating hormone reciprocally regulate nesfatin-1 neurons in the paraventricular nucleus of the hypothalamus

Nesfatin-1 is an 82 amino acids peptide processed from its precursor nucleobindin-2 (NUCB2). Accumulating evidences have shown that the nesfatin-1/NUCB2 localized in the paraventricular nucleus (PVN) of the hypothalamus regulates food intake and energy metabolism. However, the factors that regulate nesfatin-1/NUCB2 neurons in PVN are less defined. In the hypothalamic feeding center, the second-order neurons in PVN are extensively projected by the first-order neurons in the arcuate nucleus (ARC), the representatives of which are orexigenic neuropeptide Y (NPY) and anorexigenic alpha-melanocyte-stimulating hormone (alpha-MSH) neurons. The present study explored whether NPY and alpha-MSH regulate the PVN nesfatin-1/NUCB2 neurons. This was achieved by cytosolic Ca2+ ([Ca2+](i)) imaging, followed by nesfatin-1/NUCB2 immunostaining in single neurons isolated from PVN. The moderate increase in [Ca2+](i) with 5mM glucose was suppressed by NPY, but further increased by alpha-MSH in the PVN neurons that were shown to be immunoreactive to nesfatin-1/NUCB2. The majority (60%) of nesfatin-1/NUCB2 neurons in PVN responded to NPY and/or alpha-MSH. Confocal immunohistochemical images showed that both NPY and alpha-MSH neuronal terminals contacted nesfatin-1/NUCB2 neurons in PVN. These data show that NPY inhibits and alpha-MSH activates PVN nesfatin-1/NUCB2 neurons, presenting dual and reciprocal neuro-circuits from ARC to PVN, possibly contributing toward the balanced regulation of feeding. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.