Isotope Research Lab, Biological Engineering and Application Biology Department, Sichuan Agricultural University, Ya'an 625014, China.
Int J Mol Sci. 2023 Mar 2;24(5):4821. doi: 10.3390/ijms24054821.
(), a paralog of , is a newly identified gene in non-mammalian vertebrates. Limited studies in fish have evidenced its important role in food intake and energy balance modulation. However, little is known about its biological functions in birds. Using the chicken (c-) as a model, we cloned the full-length cDNA of by using RACE-PCR. It is 1189 base pair (bp) in length and predicted to generate a protein of 75 amino acids that contains a 14 amino acids mature peptide. Tissue distribution analysis showed that transcripts were detected in a wide array of tissues, with abundant expression in the pituitary, testis, and adrenal gland. was also observed to be ubiquitously expressed in chicken brain regions, with the highest expression in the hypothalamus. Its expression was significantly upregulated in the hypothalamus after 24 or 36 h of food deprivation, and the feeding behavior of chicks was obviously suppressed after peripheral injection with cSPX2. Mechanistically, further studies evidenced that cSPX2 acts as a satiety factor via upregulating cocaine and amphetamine regulated transcript () and downregulating agouti-related neuropeptide () in hypothalamus. Using a pGL4-SRE-luciferase reporter system, cSPX2 was demonstrated to effectively activate a chicken galanin II type receptor (cGALR2), a cGALR2-like receptor (cGALR2L), and a galanin III type receptor (cGALR3), with the highest binding affinity for cGALR2L. Collectively, we firstly identified that serves as a novel appetite monitor in chicken. Our findings will help clarify the physiological functions of in birds as well as its functional evolution in vertebrates.
()是一种新鉴定的非哺乳动物脊椎动物基因的旁系同源物。在鱼类中的有限研究表明其在食物摄入和能量平衡调节中具有重要作用。然而，关于其在鸟类中的生物学功能知之甚少。我们使用鸡（c-）作为模型，通过 RACE-PCR 克隆了全长 cDNA 的 。它长 1189 个碱基对（bp），预测生成一个含有 75 个氨基酸的蛋白质，其中包含 14 个氨基酸成熟肽。组织分布分析表明，在广泛的组织中检测到 转录本，在垂体、睾丸和肾上腺中表达丰富。还观察到 在鸡脑区广泛表达，在下丘脑表达最高。在 24 或 36 小时饥饿后，下丘脑的表达明显上调，而外周注射 cSPX2 后雏鸡的进食行为明显受到抑制。从机制上讲，进一步的研究表明 cSPX2 通过上调可卡因和安非他命调节转录物（）和下调刺鼠相关神经肽（）在下丘脑作为一种饱腹感因子发挥作用。使用 pGL4-SRE-荧光素酶报告系统，证明 cSPX2 可有效激活鸡甘丙肽 II 型受体（cGALR2）、cGALR2 样受体（cGALR2L）和甘丙肽 III 型受体（cGALR3），与 cGALR2L 的结合亲和力最高。总的来说，我们首次鉴定出 作为鸡的一种新型食欲监测器。我们的研究结果将有助于阐明 在鸟类中的生理功能及其在脊椎动物中的功能进化。
