The effects of exercise training on vascular function, insulin sensitivity and related genes in persons with the metabolic syndrome

The metabolic syndrome is a condition characterized by the clustering of cardiovascular risk factors including obesity, dyslipedima, hypertension and elevated glucose levels. Currently, the prevalence of the metabolic syndrome is rapidly increasing across western countries, with compelling evidence that the pathogenesis is attributable to dietary factors and lack of exercise. The metabolic syndrome has been associated with vascular endothelial dysfunction. Endothelial dysfunction is an early manifestation of atherosclerotic disease that predicts cardiovascular morbidity and mortality. The Nitric Oxide (NO)-pathway is directly related to endothelial function. Exercise training improves endothelial function possibly by improving vascular endothelial NO production. Exercise-mediated increases in NO levels may be due to an up-regulation of endothelial NO-synthase (eNOS) expression. The NO pathway is composed of a large subset of genes. It is, however, not known which genes are the primary regulators for vascular adaptations. The central aim of the present project is to identify key-genes in the NO-pathway responsible for exercise-induced improvement of the metabolic syndrome by true translational research. To this end, the effect of training in individuals with the metabolic syndrome and healthy controls on gene expression of the NO-pathway and on risk factors will be evaluated using a combined integrative-physiological and transcriptomic approach. The hypothesis of the present study is that training induces alterations in specific genes of the NO-pathway and that those changes in gene expression are related to the improvements in risk factors, such as endothelial dysfunction and insulin sensitivity, in individuals with the metabolic syndrome. The outcome of this study will provide a better understanding of the working mechanism of exercise in relation to the metabolic syndrome in humans, and will open doors to further explore the role of specific NO-related gene(s) in the metabolic syndrome, either in animal models or by drug administration, and ultimately contribute to the prevention of diabetes and cardiovascular diseases.