Weight Loss and Endothelial Function in Obesity

Endothelial dysfunction, a pathologic feature of obesity, predicts the occurrence of cardiovascular disease (1,2), and is felt to mediate the increased cardiovascular risk associated with a number of classical and nonclassical risk factors. However, the pathogenesis of endothelial dysfunction in obesity remains uncertain. In this field, the major questions center on the relative roles of insulin resistance, fatty acids, or adipocyte-associated cytokines on endothelial function. For example, a number of groups have demonstrated the ability of acute increases in circulating nonesterified fatty acids to induce insulin resistance at both the cellular and whole-body levels (3,4). The observation that such interventions also induce vascular dysfunction (5) has hinted at the mechanism of obesity-associated endothelial dysfunction, but many questions remain.

We are beginning to see studies of the effects of weight loss, achieved through a variety of means, on endothelial function in obesity. These studies are welcome for two reasons: information regarding further benefits of weight loss can help support arguments for better funding, access, and support of weight loss programs by various payors; also, there is a clear opportunity for such studies to contribute materially to our understanding of the pathogenesis of endothelial dysfunction in obesity. Weight loss is generally associated with beneficial changes in variables associated independently with endothelial dysfunction, such as blood pressure and HDL cholesterol, and such studies can therefore provide clues to the pathogenesis of endothelial dysfunction in this setting. This is something of a minefield, however, because the therapeutic lifestyle interventions usually recommended to achieve weight loss include exercise, a confounder that has well-recognized effects on endothelial function. Conversely, pharmacologically assisted weight loss must account for possible direct effects of the medication on endothelial function independent of its effects …