Adipose tissue and adipokines: for better or worse
In recent years, it has been recognized that adipose tissue (WAT) secretes a number of bioactive peptides and proteins, collectively termed “adipokines”. These WAT-derived factors play a central role in whole body homeostasis by influencing a variety of biological and physiological processes, including food intake, regulation of energy balance, insulin action, lipid and glucose metabolism, angiogenesis and vascular remodeling, regulation of blood pressure and coagulation. The present review is focused on a restricted number of adipokines, which have been implicated in vascular (angiotensinogen, PAI-1) and energy and glucose homeostasis (ASP, TNFα, IL-6, resistin, leptin, adiponectin).
As a secretory tissue, WAT displays several unusual characteristics. First, instead of being confined at a specific location, WAT is found throughout the whole organism in individual pads that are not physically connected. How adipose secretion is coordinated between depots, through humoral or nervous pathways, is still unclear. Second, WAT is constituted of distinct cell types, including mature adipocytes, pre-adipocytes, fibroblasts and macrophages, all of which participate, to a greater or lesser extent, in WAT secretory function. Third, WAT is heterogeneous in term of metabolic capacities, depending upon the visceral or subcutaneous localization of fat depots. Similarly, certain depots might contribute more actively than others to the production of specific adipokines [1, 2]. Fourth, some adipokines are also secreted by non-adipose tissues and thus it is not always straightforward to determine the specific contribution of WAT to circulating levels of these factors. Finally, little is known regarding the molecular mechanisms involved in the biosynthesis and exocytosis of adipokines, although there is evidence that regulated and constitutive secretory pathways exist in adipose cells .
It is well known that WAT mass increases greatly in obesity or, conversely, substantially shrinks in lipoatrophic syndromes. The amounts of triglyceride stored within individual adipose cells is a major determinant of WAT weight. Virtually all known adipokines are markedly dysregulated in response to alteration of WAT mass, although the molecular link between the size of adipose stores and the rate of production a specific adipokine remains, in most cases, largely speculative. Both obesity and lipoatrophy are pathologic conditions highly associated with metabolic disorders, including hyperlipidemia, insulin resistance and type 2 diabetes (T2DM), and with increased risk of cardiovascular diseases. Thus, the idea has emerged that WAT might be instrumental in the pathogenesis of these complications, by virtue of its secreted factors. This review will discuss the arguments implicating adipokines in disease states linked to altered WAT mass, which provide a rationale for therapeutic strategies targeting adipose secreted factors in obesity or lipodystrophy.