Metabolically active hormones derived from the musculoskeletal system

点击翻译按钮获取中文摘要

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.