All ETDs from UAB

Advisory Committee Chair

Barbara A Gower

Advisory Committee Members

Timothy Garvey

Douglas R Moellering

Robert Oster

Document Type

Dissertation

Date of Award

2017

Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions

Abstract

Obesity and type 2 diabetes (T2D) represent a growing global burden on healthcare and financial resources. One hypothesis for the onset and exacerbation of these diseases is related to the role of mitochondria as the end users of products of the metabolism of the nutrients we consume and in mediating the oxidative state of the body through the production of reactive oxygen species (ROS). In order to meet the demands of a metabolic challenge and prevent excessive ROS production, there appear to be adaptations to mitochondrial physiology and morphology that can occur and we hypothesize that the ability of the mitochondria to display these adaptations adequately may be imperative to maintaining cardiometabolic health. The purpose of this dissertation was to characterize mitochondrial function in response to acute and chronic stimuli relevant to the understanding of the onset and prevention of obesity and cardiometabolic diseases like T2D. We describe mitochondrial function in the context of the chronic metabolic environment promoted by obesity, the acute effect of hyperinsulinemia, and the chronic changes induced by an aerobic exercise intervention. We found that total body fat was associated with greater fatty acid oxidative capacity and coupling efficiency. Additionally, we found that an acute hyperinsulinemic event promoted ROS production and mitochondrial inefficiency. Finally, a 16-week aerobic exercise training program improved mitochondrial oxidative capacity under a fatty acid substrate, likely as a function of mitochondrial biogenesis. These data contribute to the hypothesis that the maintenance and/or restoration of mitochondrial oxidative capacity and adequate plasticity to meet both acute and chronic metabolic demands undoubtedly represents a potential target for the treatment and prevention of obesity, T2D, and other chronic diseases linked to mitochondria dysfunction and oxidative stress.

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