Alimentary myo-inositol and low phosphate in two contrasting high-yielding laying hen strains: role of alpha-Klotho/fibroblast growth factor 23 (FGF23)

FGF23(成纤维细胞生长因子23)是在哺乳动物中发现的，主要在骨骼中产生。作为一种激素，它调节肾脏对磷酸盐的重吸收和1，25(OH)2D3的形成，即生物活性维生素D。这些内分泌作用是由需要跨膜蛋白Klotho作为辅助受体的膜受体介导的。虽然FGF23作为一种疾病生物标志物在临床医学中具有很高的相关性，因为肾脏和心血管疾病与血浆FGF23的早期激增有关，但Klotho是一种强大的抗衰老因素。在蛋鸡中也检测到这两种蛋白，FGF23在肝脏表达，Klotho在肾脏表达。与哺乳动物类似，它们也参与了磷酸盐稳态的调节。然而，这些细节远没有哺乳动物的特征那么明显。本项目旨在研究(I)在高产蛋性能条件下添加肌醇对蛋鸡磷酸盐代谢调节因子Klotho和FGF23的影响，(Ii)Klotho和FGF23在因矿物质磷缺乏而被迫提高植酸(InsP6)利用率的蛋鸡中的作用，(Iii)Klotho和FGF23在缺磷蛋鸡中的遗传背景的意义，以及(Iv)Klotho和FGF23在蛋鸡对甲状旁腺激素、1，25(OH)2D3、血浆钙/磷水平(方案3)、炎症(方案7)的依赖关系AMPK和胰岛素(项目5)以及线粒体异质性(项目8)。这些研究将有助于更好地了解蛋鸡体内磷酸盐稳态的调节。这可能会带来更好的动物福利以及环境中较低的磷酸盐暴露。

FGF23 (fibroblast growth factor 23) was discovered in mammals and is mainly produced in bone. As a hormone, it regulates renal reabsorption of phosphate and formation of 1,25(OH)2D3, biologically active vitamin D. These endocrine effects are mediated by a membrane receptor requiring transmembrane protein Klotho as a co-receptor. While FGF23 is of high relevance in clinical medicine as a disease biomarker due to kidney and cardiovascular diseases being associated with early surges in plasma FGF23, Klotho is a powerful anti-aging factor. Also in laying hens, both proteins were detected with FGF23 being expressed in liver and Klotho in kidney. Similar to mammals, they are involved in the regulation of phosphate homeostasis. However, the details are far less characterized than in mammals. The project seeks to characterize (i) the impact of myo-inositol supplementation at high egg production performance on regulators of phosphate metabolism, Klotho and FGF23 in laying hens, (ii) the role of Klotho and FGF23 in laying hens forced to enhance phytic acid (InsP6) utilization due to mineral P deficiency, (iii) the significance of the genetic background of laying hens for Klotho and FGF23 in phosphorus deficiency, and (iv) the dependence of Klotho and FGF23 expression in laying hens on parathyroid hormone, 1,25(OH)2D3, plasma Ca2+/phosphate levels (project 3), inflammation (project 7), AMPK and insulin (project 5) as well as mitochondrial heteroplasmy (project 8). The investigations will contribute to a better understanding of the regulation of phosphate homeostasis in laying hens. This will likely result in better welfare of animals as well as lower phosphate exposure of the environment.