Metabolically active hormones derived from the musculoskeletal system

来自肌肉骨骼系统的代谢活性激素

• 批准号: 407162893
• 负责人: Professor Dr. Jörg Dötsch
• 金额: --
• 依托单位: Klinik und Poliklinik für Kinder- und Jugendmedizin
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/407162893?language=en
• 关键词: Metabolically; active; hormones; derived; musculoskeletal

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.

由于 FBN1 或 FBN2 的大多数突变都会导致苗条的体型和很少的皮下脂肪，因此原纤维蛋白被认为在新陈代谢和身体脂肪的调节中发挥作用。 Profibrillin-1 的 C 末端裂解产物可作为空腹诱导的生糖蛋白激素，调节肝葡萄糖释放，这一发现为这些临床发现提供了机制解释。最近，我们发现了一种控制肌肉骨骼组织中asprosin-1寡聚状态的新分子机制。我们还进一步开发了新的可靠方法，用于灵敏检测临床样本中的 asprosin-1。在这个项目中，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开辟新的治疗途径，而且还为更常见的代谢性疾病开辟新的治疗途径。