Metabolically active hormones derived from the musculoskeletal system

由于FBN1或FBN2的大多数突变导致身材苗条，皮下脂肪少，因此纤原蛋白被认为在代谢和体脂调节中发挥作用。profibrin -1的c端裂解产物作为一种空腹诱导的糖原蛋白激素，调节肝脏葡萄糖释放，为这些临床发现提供了一种机制解释。最近，我们发现了一种新的控制肌骨骼组织中asprosin-1寡聚化状态的分子机制。我们还进一步开发了新的可靠的临床样品中asprosin-1的灵敏检测方法。在本项目中，我们将研究调节asprosin-1及其同源异构体asprosin-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释放肌肉、软骨和骨骼的碎片来影响代谢健康。因此，我们的项目不仅有可能为结缔组织疾病开辟新的治疗途径，也有可能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.