Inflammatory Responses Underlying the Microvascular Dysfunction Associated with Obesity and Insulin Resistance

Obesity is a growing health care problem that is increasing the incidence and morbidity of cardiovascular diseases. Emerging evidence suggests that obesity is associated with a systemic inflammatory response that is characterized by endothelial cell dysfunction, oxidative stress, and the activation of circulating immune cells. Adipocytes produce and release a variety of cytokines (IL-1, TNF-alpha) and cytokine-like substances (leptin, resistin) that appear to mediate the inflammatory response that accompanies obesity. The abrogating influence of weight loss on the inflammatory response supports this contention. The insulin resistance that often accompanies obesity may also contribute to this inflammatory phenotype. Studies in experimental animals and clinical studies suggest that the microvascular dysfunction associated with pathological states, such as sepsis, is greatly exacerbated by obesity. Although the microvasculature appears to be a major target for the deleterious inflammatory consequences of obesity, relatively little attention has been devoted to characterizing the effects of obesity on inflammatory responses in different regional vascular beds and to defining the mechanisms that underlie the resultant microvascular dysfunction.