Chemerin Is the Adipokine Linked with Endothelin-Dependent Vasoconstriction in Human Obesity

<b>Background/Objectives</b>: The remodeling of adipose tissue occurring in obesity is associated with dysregulated production of various adipokines with vasoactive properties. Among the local mediators physiologically involved in vascular homeostasis, the endothelin (ET-1) system is upregulated in obesity, leading to vasoconstriction and vascular damage. We hypothesized that in human obesity, a link might exist between changed circulating levels of vasoactive adipokines and ET-1-dependent vasoconstriction; <b>Methods</b>: We compared plasma concentrations of selected adipokines (Luminex assay) and the vasoactive response to blockade of endothelin type A receptors (ET_A) by BQ-123 (strain-gauge plethysmography) in lean and obese individuals; <b>Results</b>: Plasma levels of adipokines with deleterious vascular actions, such as chemerin, visfatin, adipsin, and leptin, were higher in obese than in lean subjects (all <i>p</i> < 0.05). In contrast, circulating adiponectin, an adipokine with vasoprotective properties, showed no difference between groups (<i>p</i> > 0.05). The blood flow response to BQ-123 was greater in obese subjects than in lean subjects (<i>p</i> < 0.001), indicating an obesity-associated enhancement in ET-1-mediated vasoconstriction. In the entire population, circulating chemerin showed a direct correlation with the vasodilator response to BQ-123 (r = 0.30; <i>p</i> = 0.01). In contrast, no significant correlation was observed between concentrations of other adipokines and the response to BQ-123 (all <i>p</i> > 0.05). <b>Conclusions</b>: In human obesity, a direct link exists between increased circulating chemerin and augmented ET-1-mediated vasoconstriction. This observation contributes to explaining the detrimental vascular actions of chemerin and supports the view that targeting this adipokine might help prevent obesity-related vasculopathy.