The relation of adipose tissue to cardiometabolic risk.

Adipose tissue is an active and complex endocrine organ that secretes numerous bioactive substances, including hormones, growth factors, and cytokines. Central obesity, one of the components of metabolic syndrome, is a cardiometabolic risk factor associated with a state of chronic inflammation and coagulation, one in which the expression of certain adipocytokines, including tumor necrosis factor-alpha (TNF-(alpha), interleukin (IL)-6, and plasminogen activator inhibitor-1 (PAI-1) is more abundantly increased, while adiponectin expression is decreased. TNF-alpha initiates and organizes inflammatory changes in vascular tissue. IL-6, an inflammatory cytokine directly implicated in atherogenesis, exerts pleiotropic effects on a variety of tissues. An increased concentration of PAI-1, an important regulator of the endogenous fibrinolytic system, promotes continued clotting. Adiponectin, on the other hand, has potent vasculoprotective, angiogenic, anti-inflammatory, and antiatherogenic properties. Adiponectin levels are low in obese individuals and increase when weight is lost, thereby serving as a marker for cardioprotection. Weight loss has long been promoted as a means to reduce the risk of type 2 diabetes and cardiovascular disease; for example, exercise and a hypocaloric diet have been shown to decrease PAI-1 levels. Weight loss drugs, such as orlistat, a lipase inhibitor, and sibutramine, a serotonin and norepinephrine reuptake inhibitor, have both been shown to produce a decrease in C-reactive protein levels and an increase in serum adiponectin. Rimonabant, a selective cannabinoid 1 receptor antagonist in Phase III studies, also has been shown to increase adiponectin levels. These agents may play a role in the regulation of adipocytokines, which may directly affect the risk for cardiometabolic disease.