EXERCISE AND OXIDATIVE STRESS MECHANISMS IN CHILDREN WITH THE METABOLIC SYND

University Of California-Irvine, Irvine CA

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Abstract

The metabolic syndrome (MS) is a cluster of metabolic abnormalities [obesity, dyslipidemia, hypertension[unreadable] and hyperglycemia] predisposing to increased incidence of type 2 diabetes and cardiovascular mortality.[unreadable] Alarmingly, the incidence of the MS is insidiously increasing among children and adolescents, setting the[unreadable] stage for unprecedented levels of cardiovascular and metabolic disease in the future, with then potential for[unreadable] staggering morbidity and social costs. Many pathogenetic aspects of the MS are still unclear, but oxidative[unreadable] stress (OS), an imbalance between production of reactive oxygen species (ROS) and antioxidant defenses,[unreadable] is emerging as a major potential mechanism. While physical activity and nutrition are well known naturally[unreadable] occurring modifiers of ROS production and anti-oxidant defenses, in children key mechanisms governing the[unreadable] interactions among exercise, diet, and oxidative pathways, and the influence of these variables on the onset[unreadable] and comorbidities of the MS, have yet to be investigated. The fundamental premise of our research is that[unreadable] physical inactivity, high-fat diet and obesity all conspire to impair the regulation of OS in children. This[unreadable] general hypothesis can be tested using exercise as a quantifiable and reproducible experimental[unreadable] perturbation, due to its unique ability to stimulate, even in brief bouts, two main sources of ROS--[unreadable] mitochondrial O2 flow and neutrophils (the latter, part of the stress/inflammatory response now known to[unreadable] occur with exercise in children). We propose that each of these key mechanisms (physical inactivity, high fat[unreadable] diet, obesity) impairs the balance between ROS generation and antioxidant defenses, rendering the child[unreadable] more vulnerable to the damaging effects of OS. Children will be challenged with specially designed exercise[unreadable] protocols, while all major variables associated with oxidative activity (oxidation of lipids, glucose, proteins,[unreadable] nitric oxide, DNA; neutrophil oxidative activity and gene expression, systemic antioxidants levels) will be[unreadable] simultaneously monitored. The following specific hypotheses will be tested: a) that even in the healthy child,[unreadable] a marked influence on oxidative processes during exercise is exerted by gender, maturational status and[unreadable] degree of physical fitness; b) that the transient hyperlipidemia caused by a high fat meal can acutely and[unreadable] measurably increase exercise-induced oxidative stress; and c) that pediatric obesity and metabolic[unreadable] syndrome are associated with exaggerated resting and exercise-induced oxidative stress. The PPG is[unreadable] uniquely suited for this challenging project, combining the experiences in pediatric and diabetic exercise[unreadable] testing of our human performance laboratory and metabolic core, with the expertise in oxidative marker[unreadable] analysis of three different laboratories, all collaborating in the project. Based on new and exciting preliminary[unreadable] studies, this research is aimed at defining these previously unexplored mechanisms, optimizing the use of[unreadable] exercise and diet, both diagnostically and therapeutically, to prevent or attenuate the deleterious health[unreadable] consequences of the metabolic syndrome in children.