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.

Proopiomelanocortin（POMC）是垂体前叶和垂体中叶，下丘脑弓状核（ARC）和孤立道核中产生的一种神经肽前体。α-黑素细胞刺激激素（α-MSH）是特定于细胞类型的POMC衍生物，对于调节进食和能量稳态至关重要。然而，POMC /α-MSH分泌的分子机制尚不清楚。Ca ²⁺依赖性分泌蛋白2（CAPS2）是一种调节蛋白，参与含有神经肽的致密囊泡的胞吐作用。先前我们报道了CAPS2在垂体中叶的局部化和Caps2敲除（Caps2-KO）小鼠，与对照小鼠相比。在这里，我们旨在调查CAPS2在表达POMC的神经元中的表达以及CAPS2缺乏对POMC相关肽的分泌和进食行为表型的影响。CAPS2位于下垂体中叶，下丘脑ARC和下丘脑旁神经元的表达POMC的神经元中。Caps2- KO小鼠的脑垂体中叶中的POMC蛋白水平显着高于对照小鼠，这表明Caps2- KO小鼠的脑垂体中叶中可能存在POMC衍生肽的积累。此外，在Caps2中服用低剂量的melanotan-2（一种α-MSH受体（MC4R）激动剂）可减少单位体重的食物摄入量-KO小鼠；在野生型小鼠中未观察到这种作用。总的来说，这些结果表明CAPS2参与调节POMC衍生肽（包括α-MSH）的分泌，与进食部分相关，并影响能量代谢。