The adipocyte as a secretory organ: Mechanisms of vesicle transport and secretory pathways

Obesity is a common problem in western society that is directly linked to s everal disease processes and is associated with significant morbidity and m ortality. Adipocytes - the primary site for energy storage (as triglyceride s) and release - were long suspected to have an active role in regulating b ody weight homeostasis and energy balance. As a result, many studies have f ocused on finding abnormalities in adipocyte physiology and metabolism An e ver-increasing body of evidence indicates that, in addition to serving as a repository for energy reserves, adipocytes secrete a myriad of factors tha t comprise a complex network of endocrine, autocrine, and paracrine signals . Very little is known regarding the molecular mechanisms utilized by the a dipocyte in regulating the biosynthesis and exocytosis of these secreted pr oducts. In order to gain a better understanding of these processes, we have examined the two classical secretory pathways: regulated and constitutive. Using leptin as a model adipocyte-secretory protein, this review focuses p rimarily on the latter pathway. This includes regulation of leptin synthesi s and secretion by insulin and glucocorticoids and, more recently, the find ing that the orexigenic neuropeptide, melanin-concentrating hormone (MCH), can stimulate leptin synthesis and secretion, This chapter also incorporate s new data describing the partial purification and effect of insulin on lep tin-containing vesicles in rat adipocytes. These data indicate that the maj ority of leptin trafficking occurs via a constitutive secretory pathway and that the primary acute insulin effect on leptin secretion is to increase l eptin protein content. In addition, we describe the identification and char acterization of the vesicle-associated protein, pantophysin, which may play a multifunctional role in vesicle biogenesis and transport.