| First Author | Fujima S | Year | 2020 |
| Journal | Neurosci Lett | Volume | 738 |
| Pages | 135335 | PubMed ID | 32891671 |
| Mgi Jnum | J:298697 | Mgi Id | MGI:6477161 |
| Doi | 10.1016/j.neulet.2020.135335 | Citation | Fujima S, et al. (2020) CAPS2 deficiency induces proopiomelanocortin accumulation in pituitary and affects food intake behavior in mice. Neurosci Lett 738:135335 |
| abstractText | Proopiomelanocortin (POMC) is a neuropeptide precursor produced in the anterior and intermediate pituitary lobes, the hypothalamic arcuate nucleus (ARC), and solitary tract nucleus. Alpha-melanocyte-stimulating hormone (alpha-MSH) is a cell type specific POMC derivative that is essential for regulating feeding, and energy homeostasis. However, the molecular mechanism underlying POMC/alpha-MSH secretion remains unclear. Ca(2+)-dependent activator protein for secretion 2 (CAPS2) is a regulatory protein involved in the exocytosis of dense-core vesicles containing neuropeptides. We previously reported CAPS2 localization in the intermediate pituitary lobe and reduced body weights in Caps2-knockout (Caps2-KO) mice, compared to control mice. Here, we aimed to investigate CAPS2 expression in POMC-expressing neurons and the effects of CAPS2 deficiency on the secretion of POMC-related peptides and feeding behavior phenotype. CAPS2 was localized in the POMC-expressing neurons of the intermediate pituitary lobe, hypothalamic ARC, and the paraventricular nucleus, which is innervated by hypothalamic neurons. POMC protein levels in the intermediate pituitary lobe of Caps2-KO mice were significantly higher than that in the control mice, suggesting a possible accumulation of POMC-derived peptides in the intermediate pituitary lobe of Caps2-KO mice. Moreover, administration of low-dose melanotan-2, an alpha-MSH receptor (MC4R) agonist, decreased food intake per body weight in Caps2-KO mice; no such effect was observed in the wildtype mice. Collectively, these results suggest that CAPS2 is involved in regulating the secretion of POMC-derived peptides, including alpha-MSH, is partially associated with feeding, and affects energy metabolism. |
