Unconventional protein secretion from adipocytes

Abstract

Endocrine function of the adipose tissue plays a major role in maintaining energy balance and glucose homeostasis by releasing a large number of bioactive proteins. Any dysfunction of the endocrine function of the adipose tissue caused due to obesity will initiate pathophysiological changes and hasten disease progression. In this thesis, I focus on the secretion of leaderless proteins from the primary cells of the adipose tissue, the adipocytes. This secretion process is called unconventional protein secretion (UPS) and as shown here for the first time, our results indicate that the UPS is highly regulated and a variety of proteins are secreted upon the adipocyte receiving a lipolytic stimuli. To characterize the UPS, we followed the secretion pathway of unconventionally secreted adipocyte fatty acid binding protein (FABP4). FABP4 is one of the majorly expressed protein in mature adipocytes whose intracellular function is lipid storage and trafficking. Increasing evidence indicates that FABP4 has multiple functions extracellularly and is strongly associated with metabolic disease progression. Our results elucidate the regulation and mechanism of UPS/FABP4 secretion pathway. Unraveling the role of UPS proteins in the circulation and integrating them as a systemic response will be central to our understanding of the balance between healthy and unhealthy states. Such a study will be more insightful in predicting metabolic diseases than analyzing different individual marker proteins in the blood stream at a time for various pathologies.