Dietary Fructose as a Risk Factor for Gulf War Illness: Exercise Challenge

Grant Winners

Jacqueline Freire Machi, Ph.D. – College of Osteopathic Medicine
Mariana Morris, Ph.D. – College of Osteopathic Medicine
Mary Ann Fletcher, Ph.D. – College of Osteopathic Medicine
Nancy Klimas, M.D. – College of Osteopathic Medicine
Luis M. Salgueiro, Ph.D. – College of Osteopathic Medicine
Rodrigo Schmidt, M.S. – College of Osteopathic Medicine
Christopher Elkins, B.S. – College of Osteopathic Medicine

Dean

Elaine Wallace, D.O., M.S., M.S., M.S. – College of Osteopathic Medicine

Abstract

Gulf War illnesses (GWI), is a chronic disorder affecting returning military veterans and civilian workers of the 1990–91 Gulf War. A wide range of acute and chronic symptoms have been linked to it, including fatigue, muscle pain, cognitive problems, rashes and autonomic imbalance. Most studies of GWI have focused on pesticide exposure. However, this does not take into consideration of environmental factors. Recent studies suggest that a high intake of refined carbohydrates such as found in soft drinks and juice, as well as processed food may increase the risk of cardiovascular diseases and exacerbate the GWI scenario. The literature documents that the GWI population has chronic multi symptom illness, which may include metabolic syndrome (MS). We propose to use an organophosphate Diisopropyl fluorophosphate (DFP) to develop an animal model of GWI this will be coupled with a high fructose diet to develop MS and exacerbate the GWI characteristic. Aerobic exercise training has been recommended as an important adjuvant therapy for the prevention and treatment of different disorders such as metabolic and cardiovascular dysfunction. The aim of this proposal is to use a GWI +MS mouse model to study metabolic/cardiovascular and neuro-inflammatory profiles as well to test the effects of chronic aerobic exercise as a possible treatment. Indeed, our preliminary results in mice suggest that low doses of DFP was able to cause reduction in cardiac output (CO), Ejection Fraction (EF), Fractional Shortening (FS) and a generalized dilation. The development of models to study the pathophysiology of GWI will help in developing of effective therapies for human, which may lead to improvement quality life of the affected population. In the study mice will be evaluated at baseline, one week after toxin/fructose exposure (GWI + MS) followed by the exercise protocol. Studies will use transthoracic echocardiography (ECHO) to access cardiac function and autonomic balance. Metabolism will be assessed by calorimetry (O2 consumption and CO2 production). Immunological markers will be measured in blood and tissue. Obesity will be evaluated by magnetic resonance imaging. Tissue histologic/morphometric analysis will be performed to evaluate tissue damage. Exercise will be performed with a wheel running setup along with measures of O2 consumption. Studies will document the idea that an overload in fructose will lean to a decrement in cardiac and metabolic function. On the other hand, the exercise model will have the opposite effect and improvement in function. This study can have relevance to human condition in which chemical toxins are often coupled with the sugar-laden diet.