From Adipose Tissue Protein Secretion to Adipopharmacology of Disease

An extensive research in the last few years has identified about hundred adipose tissue-secreted proteins, named adipokines or adipocytokines. However, our knowledge of the structures and molecules involved in the intracellular secretory pathway (synthesis, translocation, folding, targeting, sorting, storage, and exocytosis) of adipokines is at present limited. Relatively more is known about insulin-responsive trafficking of glucose transporters (GLUTs). Adipokines have multiple biological functions beyond lipid and carbohydrate metabolism, whereas GLUT4 is the major glucose transporter of adipocytes and skeletal muscles. Adipokines play an important role in the pathogenesis of a wide variety of diseases, and dysregulation of GLUT4 transport is implicated in insulin resistance and related disorders. Conceptually, adipobiology of disease has emerged as a novel field of studies in basic and clinical medicine. Here we present a state-ofthe- science on some aspects of these studies with a special reference to the intracellular secretory pathway, focusing on adiponectin, GLUT4, and nerve growth factor (NGF), and suggesting that each step of this pathway may be a potential drug target. Given the beneficial effects of adiponectin, NGF and GLUT4 on various metabolic, vascular and inflammatory processes, a hypothesis of metabotrophic factor deficit in the pathogenesis of adipose-linked diseases is discussed. Adipopharmacological evaluation of this hypothesis may provide novel targets for drug development.