CAPS2 deficiency induces proopiomelanocortin accumulation in pituitary and affects food intake behavior in mice.

Shuhei Fujima, Natsuki Amemiya, Tomoki Arima, Yoshitake Sano, Teiichi Furuichi

Neuroscience letters 2020 Nov 01

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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 (α-MSH) is a cell type specific POMC derivative that is essential for regulating feeding, and energy homeostasis. However, the molecular mechanism underlying POMC/α-MSH secretion remains unclear. Ca2+-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 α-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 α-MSH, is partially associated with feeding, and affects energy metabolism. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Shuhei Fujima, Natsuki Amemiya, Tomoki Arima, Yoshitake Sano, Teiichi Furuichi. CAPS2 deficiency induces proopiomelanocortin accumulation in pituitary and affects food intake behavior in mice. Neuroscience letters. 2020 Nov 01;738:135335