Endothelial Cell IL-8, a New Target for Adiponectin

dipose tissue is no longer considered an inert energy storage tissue, but an active participant contributing to physiological and pathological processes associated with inflammation, immunity, appetite, insulin sensitivity, endocrine and reproductive systems, bone metabolism, and endothelial function.1,2 Adipose tissue synthesizes and secretes proinflammatory and antiinflammatory metabolically-and hormonally-active substances, collectively called adipokines or adipocytokines and include leptin, adiponectin, resistin, and visfatin.3,4 Adipose tissue also produces cytokines and chemokines, such as tissue necrosis factor (TNF)-1␣, interleukin (IL)-1␤, IL-6, IL-8, IL-10, transforming growth factor (TGF)-␤, nerve growth factor and the acutephase response plasminogen activator inhibitor-1, haptoglobin, and serum amyloid.1,2,5 Although adipose tissue produces various polypeptide and non-protein factors, only leptin, adiponectin, resistin, adipsin, and visfatin are primarily synthesized by adipocytes.3,4 Whereas leptin plays a role mainly in appetite regulation, 6 resistin induces insulin resistance and is proinflammatory 7 whereas visfatin acts as an insulinmimetic and is antiapoptotic.8 Of all the adipokines, adiponectin is found in highest concentrations in the circulation.9 It is secreted specifically from adipocytes and it regulates insulin sensitivity.10 Low serum levels are causally linked to insulin resistance, obesity, and type 2 diabetes and are predictive for development of diabetes and cardiovascular disease.11,12 Obesity is associated with decreased adiponectin levels, and adiponectin is now being considered a putative therapeutic agent in the management of obesity.13,14 Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice.15,16 Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes.17,18 This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase 19 and peroxisome proliferator-activated receptor-␥ (PPAR-␥).20 Emerging evidence indicates that adiponectin has functions beyond insulin modulation.Recent studies demonstrated that adiponectin is synthesized and secreted not only by adipo-The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.