Abstract
Evidence shows that both poor physical fitness and obesity are linked to low-grade inflammation and inflammatory diseases. However, their relative roles on inflammation and underlying mechanisms remain unclear. Given the inhibitory effect of catecholamines on inflammatory cytokine production, we speculated that compromised responsiveness of immune cells' beta adrenergic receptors (β-ARs) to agonists may be associated with constitutively elevated levels of inflammatory cytokines. We examined circulating levels of inflammatory cytokines TNF, IL-1β, IL-6 and β-AR sensitivity of, 70 overweight or obese compared to 26 normal-weight, otherwise healthy individuals in order to investigate the associations among obesity, physical fitness, and low-grade inflammation and to examine the role of β-ARs in these relationships. Cardiorespiratory fitness was determined by VO2peak (ml/kg/min) via a treadmill exercise. Beta-AR sensitivity was evaluated by measuring the degree of inhibition in lipopolysaccharides-stimulated monocytic intracellular TNF production by isoproterenol. In all participants, BMI, which was initially a predictor of IL-1β and IL-6 levels independent of demographic characteristics, no longer significantly predicted them after controlling for fitness levels. Among the overweight or obese participants, greater cardiorespiratory fitness was a strong predictor of lower levels of TNF and IL-1β after controlling for the covariates. When β-AR sensitivity was controlled for, however, fitness was no longer a significant predictor of those cytokines. Monocytic β-AR sensitivity was negatively associated with inflammatory marker levels and diminished in obese individuals; however, when fitness was controlled for, the significant weight group differences in β-AR sensitivity disappeared. Our findings indicate that better cardiorespiratory fitness protects against obesity-related low-grade inflammation and β-AR desensitization. Given the significance of β-AR function in pathogenesis of various diseases, clinical implications of its role in the fitness-inflammation association among the obese are profound.