Noradrenaline-mediated inhibition of inflammatory cytokines is altered in macrophages from obese Zucker rats: effect of habitual exercise.

The obese Zucker rat (fa/fa) (ObZ) is a good animal model for Metabolic Syndrome (MS)-associated neuroendocrine and inflammatory disorders. The aim of the present investigation was to evaluate the effect of noradrenaline (NA) on the release of IL-1β, IL-6 and TNFα by macrophages from ObZ, as well as the effect of habitual exercise (running, 5days/week for 35 min at 35cm/s for 14week); all of them using lean Zucker rats (Fa/fa) (LZ) as reference values. Cytokines were determined by ELISA in the supernatants of macrophages cultured for 24h (37°C, 5% CO2 and 100% RH) in presence or absence of 10(-5)M NA. Both the spontaneous and NA-induced release of IL-1β and IL-6 were higher in sedentary obese (ObSZ) rats than in healthy LZ rats (a significant lower spontaneous production of TNFα was also found in the ObSZ rats). While the NA-induced release of IL-1β was higher in the exercised obese (ObTZ) rats, the NA-induced production of IL-6 was lower compared with ObSZ rats. In addition, NA has an inhibitory role on the release of IL-1β and TNFα (with respect to the spontaneous release) in both lean and obese (sedentary and exercised) rats. However, NA inhibits the IL-6 production by macrophages from lean and exercised obese animals, but promotes IL-6 release in the sedentary obese rats. In conclusion, an altered inflammatory response of macrophages mediated by NA is underlying in MS, and this regulation is improved after regular exercise, particularly on IL-6.