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

FGF 23（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，它调节磷酸盐的肾重吸收和1，25（OH）2D 3（生物活性维生素D）的形成。这些内分泌效应由膜受体介导，需要跨膜蛋白Klotho作为共受体。虽然FGF 23在临床医学中作为疾病生物标志物具有高度相关性，因为肾脏和心血管疾病与血浆FGF 23的早期激增相关，但Klotho是一种强大的抗衰老因子。同样在产蛋鸡中，检测到两种蛋白质，其中FGF 23在肝脏中表达，Klotho在肾脏中表达。与哺乳动物相似，它们参与磷酸盐稳态的调节。然而，细节远不如哺乳动物的特征。该项目旨在表征（i）在产蛋性能高的情况下补充肌醇对产蛋鸡中磷酸盐代谢调节剂Klotho和FGF 23的影响，（ii）Klotho和FGF 23在产蛋鸡中的作用，由于矿物质P缺乏，（iii）产蛋鸡的Klotho和FGF 23的遗传背景在磷缺乏中的意义，以及（iv）产蛋鸡中Klotho和FGF 23表达对甲状旁腺激素1，25（OH）2D 3的依赖性，血浆Ca 2 +/磷酸盐水平（项目3）、炎症（项目7）、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产蛋鸡体内磷平衡的调节。这可能会导致更好的动物福利以及更低的磷酸盐暴露环境。

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.