All ETDs from UAB

Advisory Committee Chair

Gordon Fisher

Advisory Committee Members

Brenda B Bertrand

Douglas Moellering

Jose R Fernandez

Rakesh P Patel

Document Type

Dissertation

Date of Award

2020

Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions

Abstract

Obesity ranks among the top growing health concerns worldwide. The prevalence of obesity at all life stages continues to rise with nearly 40% of adults and 35% of children/adolescents being affected. Equally troublesome is the increased risk for a number of comorbidities associated with obesity including cardiovascular disease, stroke, type 2 diabetes mellitus, and certain types of cancer. The successful treatment of obesity, particularly long-term, continues to prove challenging and is often met with limited success. This highlights the importance of continued investigation into alternative strategies that may reduce the incidence and severity of obesity and associated pathophysiologies. Regular physical exercise has been shown to reduce the incidence of obesity and assist in weight maintenance following weight loss. However, the biological consequences of obesity often make participation in exercise more difficult and burdensome, resulting in abstention and increased sedentarism. Nitric oxide (NO) is a vital, pleiotropic molecule with a variety of regulatory roles in human physiology and exercise performance. There is evidence to suggest that individuals with obesity have reduced NO bioavailability and bioactivity contributing to, and exacerbating the condition of obesity and associated exercise intolerance. The purpose of this dissertation was to examine the effects of dietary nitrate supplementation (in vivo reduction to NO) for improving cardiometabolic health and exercise tolerance in individuals with obesity, and to examine/characterize the obligatory role of oral nitrate-reducing microbes in this process. Using a cross-sectional design, we found a number of both positive and negative relationships between abundance of specific oral bacteria, and nitrate-reductase activity, and identified age-associated changes in nitrate-reductase activity. Additionally, using a randomized, crossover study design, we found supplementation with nitrate-rich beetroot juice improved sub-maximal exercise efficiency and exercise tolerance in individuals with obesity. Together, these data contribute to the hypothesis that improving NO status via the bacterially mediated nitrate-nitrite-NO pathway, may be an effective strategy for improving exercise outcomes in individuals with obesity. Further, by characterizing age, and bacteria-specific relationships with nitrate-reductase activity, we gain valuable insight into possible areas for future research involving pre and probiotic therapies to maximize the health and effectiveness of these critical oral microbes.

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