Adipokines as novel biomarkers and regulators of the metabolic syndrome

Over the past two decades our view of adipose tissue has undergone a dramatic change from an inert energy storage tissue to an active endocrine organ. Adipose tissue communicates with other central and peripheral organs by synthesis and secretion of a host of molecules that we generally refer to as adipokines. The levels of some adipokines correlate with specific metabolic states and have the potential to impact directly upon the metabolic homeostasis of the system. A dysregulation of adipokines has been implicated in obesity, type 2 diabetes, hypertension, cardiovascular disease, and an ever-growing larger list of pathological changes in a number of organs. Here, we review the recent progress regarding the synthesis, secretion, and physiological function of adipokines with perspectives on future directions and potential therapeutic goals. Adipose tissue has been recognized as an active endocrine organ in addition to its role as the main storage depot for triglycerides.1 An increasing number of adipocyte-derived secretory factors ("adipokines") are described in the literature,2,3 highlighting the central role of adipose tissue in regulating whole body energy homeostasis, not only by partitioning lipids into various depots, but also through adipokine-mediated modulation of a number of signaling cascades in target tissues. It is well-established that individuals that are obese and/or suffer from the metabolic syndrome display a characteristic imbalance of their adipokine profile. This altered adipokine profile leads to profound changes in insulin sensitivity and other biochemical alterations of metabolites, making an individual more prone to metabolic disorders. Through their autocrine, paracrine, and endocrine functions, adipokines influence a number of organs critical for energy homeostasis. The changes in each individual adipokine are the result of a coordinated change of specific transcriptional programs that affect entire groups of adipocyte gene products as well as posttranslational mechanisms that affect the release of specific proteins differentially. Among these adipokines, adiponectin is one of the most potent molecules with respect to its insulin-sensitizing activity. However, unlike the vast majority of adipocyte-derived factors, the levels of adiponectin in circulation display an inverse correlation with adiposity. Given the established beneficial roles of adiponectin on whole body metabolism and its profound protective effects against many chronic diseases, a better understanding of the regulation of adiponectin secretion is very important. Here, we focus on the regulation of adiponectin secretion from the adipocyte as a paradigm of protein release from the secretory pathway of the adipocyte and the changes it undergoes in the context of obesity and other pathological settings. Beyond the mechanics of protein release, we will extend the discussion to other recent developments in the area of adipokines and their effects on metabolism.