Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
Peptides. 2021 Jul;141:170551. doi: 10.1016/j.peptides.2021.170551. Epub 2021 Apr 17.
Energy homeostasis is is determined by food intake and energy expenditure, which are partly regulated by the cross-talk between central and peripheral hormonal signals. Phoenixin (PNX) is a recently discovered pleiotropic neuropeptide with isoforms of 14 (PNX-14) and 20 (PNX-20) amino acids. It is a potent reproductive peptide in vertebrates, regulating the hypothalamo-pituitary-gonadal axis (HPG). It has been identified as a regulator of food intake during light phase when injected intracerebroventricularly in rats. In addition, plasma levels of PNX also increased after food intake in rats, suggesting that it might have possible roles in energy homeostasis. We hypothesized that gut is a source and site of action of PNX in mice. Immunoreactivity for PNX and its putative receptor, super-conserved receptor expressed in brain (SREB3; also known as the G-protein coupled receptor 173/GPR 173) was found in the stomach and intestine of male C57/BL6 J mice, and in MGN3-1 (mouse stomach endocrine) cells and STC-1 (mouse enteroendocrine) cells. In MGN3-1 cells, PNX-20 significantly upregulated ghrelin (10 nM) and ghrelin-O-acyl transferase (GOAT) mRNAs (1000 nM) at 6 h. In STC-1 cells, it significantly suppressed CCK (100 nM) at 2 h. No effects were found on other intestinal hormones tested (glucagon like peptide-1, glucose dependent insulinotropic polypeptide, and peptide YY). Together, these results indicate that PNX-20 is produced in the gut, and it could act directly on gut cells to regulate metabolic hormones.
能量平衡由食物摄入和能量消耗决定,而这些部分受中枢和外周激素信号的相互作用调节。凤凰素(PNX)是一种最近发现的具有多功能的神经肽,有 14 个(PNX-14)和 20 个(PNX-20)氨基酸的同工型。它是脊椎动物中一种有效的生殖肽,调节下丘脑-垂体-性腺轴(HPG)。在大鼠的侧脑室注射时,它被鉴定为光周期期间食物摄入的调节剂。此外,在大鼠进食后,血浆中 PNX 的水平也增加,这表明它可能在能量平衡中具有潜在作用。我们假设肠道是 PNX 在小鼠中的来源和作用部位。在雄性 C57/BL6 J 小鼠的胃和肠道中,以及在 MGN3-1(小鼠胃内分泌)细胞和 STC-1(小鼠肠内分泌)细胞中,发现了 PNX 及其假定受体超级保守脑表达受体(SREB3;也称为 G 蛋白偶联受体 173/GPR 173)的免疫反应性。在 MGN3-1 细胞中,PNX-20 在 6 小时时显著上调了 ghrelin(10 nM)和 ghrelin-O-酰基转移酶(GOAT)mRNA(1000 nM)。在 STC-1 细胞中,它在 2 小时时显著抑制 CCK(100 nM)。在测试的其他肠激素(胰高血糖素样肽-1、葡萄糖依赖性胰岛素释放肽和肽 YY)中未发现作用。总之,这些结果表明 PNX-20 在肠道中产生,它可以直接作用于肠道细胞来调节代谢激素。