The interleukin-6 and noradrenaline mediated inflammation-stress feedback mechanism is dysregulated in metabolic syndrome: Effect of exercise

BACKGROUND: Metabolic syndrome (MS) is a metabolic disorder associated with obesity, type-II diabetes, and "low grade inflammation", with the concomitant increased risk of cardiovascular events. Removal of the inflammatory mediator signals is a promising strategy to protect against insulin resistance, obesity, and other problems associated with MS such as cardiovascular disease. The aim of the present investigation was to determine the "inflammatory and stress status" in an experimental model of MS, and to evaluate the effect of a program of habitual exercise and the resulting training-induced adaptation to the effects of a single bout of acute exercise. METHODS: Obese Zucker rats (fa/fa) were used as the experimental model of MS, and lean Zucker rats (Fa/fa) were used for reference values. The habitual exercise (performed by the obese rats) consisted of treadmill running: 5 days/week for 14 weeks, at 35 cm/s for 35 min in the last month. The acute exercise consisted of a single session of 25-35 min at 35 cm/s. Circulating concentrations of IL-6 (a cytokine that regulates the inflammatory and metabolic responses), CRP (a systemic inflammatory marker), and corticosterone (CTC) (the main glucocorticoid in rats) were determined by ELISA, and that of noradrenaline (NA) was determined by HPLC. Glucose was determined by standard methods. RESULTS: The genetically obese animals showed higher circulating levels of glucose, IL-6, PCR, and NA compared with the control lean animals. The habitual exercise program increased the concentration of IL-6, PCR, NA, and glucose, but decreased that of CTC. Acute exercise increased IL-6, CRP, and NA in the sedentary obese animals, but not in the trained obese animals. CTC was increased after the acute exercise in the trained animals only. CONCLUSION: Animals with MS present a dysregulation in the feedback mechanism between IL-6 and NA which can contribute to the systemic low-grade inflammation and/or hyperglycaemia of MS. An inappropriate exercise intensity can worsen this dysregulation, contributing to the metabolic, inflammatory, and stress disorders associated with MS. Habitual exercise (i.e., training) induces a positive adaptation in the response to acute exercise.