Metabolically active hormones derived from the musculoskeletal system

由于FBN 1或FBN 2中的大多数突变导致具有很少皮下脂肪的苗条体型，因此已提出原纤维蛋白在代谢和体脂调节中发挥作用。这些临床结果的机制解释是发现proglycin-1的C-末端裂解产物作为一种空腹诱导的生糖蛋白激素，调节肝脏葡萄糖释放。最近，我们发现了一个新的控制肌肉骨骼组织中白色脂肪肽-1寡聚化状态的分子机制。我们还进一步开发了新的和可靠的方法，用于灵敏地检测临床样品中的白色脂肪肽-1。在这个项目中，我们将研究调节白色脂肪肽-1及其同源异构体白色脂肪肽-2的生物利用度和细胞反应的分子机制。在这里，我们的中心假设是，肌肉骨骼系统通过从肌肉、软骨和骨骼释放碎片来影响代谢健康。因此，我们的项目有可能不仅为结缔组织疾病，而且为更常见的代谢疾病开辟新的治疗途径。

Since most mutations in FBN1 or FBN2 result in a slender habitus with little subcutaneous fat, fibrillins have been proposed to play in a role in metabolism and the regulation of body fat. A mechanistic explanation for these clinical findings was provided by the discovery that the C-terminal cleavage product of profibrillin-1 serves as a fasting-induced glucogenic protein hormone that modulates hepatic glucose release. Recently, we have uncovered a new molecular mechanism controlling the oligomerization state of asprosin-1 in musculoskeletal tissues. We also further developed new and reliable methods for the sensitive detection of asprosin-1 in clinical samples. In this project, we will investigate the molecular mechanisms that regulate the bioavailability and cellular responses of asprosin-1 and its homologous isoform asprosin-2. Here, our central hypothesis is that the musculoskeletal system impacts metabolic health by releasing fragments from muscle, cartilage and bone. Thus, our project has the potential to open up new therapeutic avenues not only for connective tissue disorders, but also for more common metabolic disorders.