Browsing by Subject "aerobic exercise"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Development and Deployment of Untargeted Metabolomics Pipelines to Reveal Molecular Signatures of Wellness
    (2022-08) Nelson, Alisa
    Metabolomics technologies hold significant potential for aiding research in the underlying drivers of metabolic disease. However, the complexity of metabolomics data sets can limit their impact. This thesis combines computational biology with analytical chemistry and metabolic physiology to deploy metabolomics pipelines directed toward two significant research problems: (i) distinguishing the serum metabolome of normal weight and overweight or obese trained runners; (ii) developing bioinformatic pipelines using stable isotopes to improve feature selection and elucidate metabolite-metabolite relationships.Previously, metabolomics tools have been applied to measure the differences between metabolically healthy (MHO) and metabolically unhealthy obesity (MUO), or untrained versus trained groups. However, how well-trained MHO groups respond to acute exercise is yet unknown. Using liquid chromatography-high resolution mass spectrometry- based untargeted metabolomics, multidimensional mass spectrometry-based shotgun lipidomics, correlation analysis and machine learning models, the effect of increased adiposity and acute exercise on trained runners are evaluated. Fatty acid esters of hydroxy fatty acids (FAHFAs), an anti-diabetic and anti-inflammatory lipid class, distinguish normal weight (NWT) and overweight/obese trained (OWT) runners who differ in body composition but have similar levels of cardiovascular fitness. Many diverse FAHFA species are elevated at baseline and decrease with acute running in NWT, but not OWT. These exercise-induced changes are inversely associated with changes in IL-6, a known myokine involved in inflammatory pathways, and are influenced by visceral fat mass. Baseline concentrations of FAHFAs are negatively associated with visceral fat mass and together with free fatty acids and purine nucleosides account for 53% of the variation in VO2max in this cohort. Finally, the formation of isobaric FA dimers in untargeted metabolomics pipelines when fatty acids are abundant necessitate the use of targeted measurement of FAHFAs in serum for accurate quantitation. This work reveals a novel role of FAHFAs in acute exercise adaptation that is affected by increased adiposity. These results may direct future research in the treatment of obesity and its related complications. Moreover, this thesis provides a rigorous approach to validating biologically significant features the broader metabolomics community can mimic in future untargeted studies.
  • Thumbnail Image
    Item
    Variability in Exercise Responsiveness Among Older Adults: An Examination of Predictors and Patterns of Nonresponse to Exercise in Peripheral Artery Disease
    (2019-07) Whipple, Mary
    Background: Despite the significant inter-individual variability observed in outcomes of aerobic exercise programs among older adults, little is known about the prevalence of nonresponse to exercise in this population. Supervised exercise therapy (SET) is the primary guideline-recommended therapy for the treatment of symptomatic peripheral artery disease (PAD), yet variability in response to outcomes in this population is not well understood. Previous research suggests that individuals with PAD and comorbid diabetes may be less likely to see a benefit in physical function and quality of life outcomes following SET, yet few studies have been designed to directly compare outcomes in these populations, and no studies have examined the potential role of changes in sedentary time during the course of SET in SET outcomes. Additionally, it is unknown if patterns exist in inter- and intra-individual response across a variety of outcomes. Findings of such research could enable informed tailoring of exercise therapy programs to maximize an individual’s potential benefit. Aims: This dissertation aimed to (1) determine the prevalence of nonresponse to aerobic exercise among older adults participating in studies of aerobic exercise programs, and identify factors related to nonresponse that have been examined in the literature; (2) quantify changes in sedentary behavior among older adults with PAD, with and without diabetes, engaging in SET for the management of symptomatic PAD and examine how diabetes and changes in sedentary time are related to SET outcomes; and (3) examine the prevalence of nonresponse to SET among individuals with PAD and explore patterns of nonresponse across of a variety of relevant objective and self-reported outcomes. Methods: Aim 1. A critical review of published studies in which the authors examined variability in response, poor response, or lack of response to aerobic exercise interventions in older adults was conducted. Methods of defining nonresponse, the prevalence of nonresponse, and factors associated with nonresponse are discussed. Aim 2. A pre-test post-test study of older adults (n = 44) initiating a 12-week SET program for symptomatic PAD was conducted in a midwestern hospital system. Participants completed assessments of physical function (six-minute walk test, Short Physical Performance Battery, Walking Impairment Questionnaire), and physical activity and sedentary behavior (assessed objectively via wrist-worn accelerometer) at the time of SET initiation, 6 weeks, and 12 weeks. Changes in sedentary time overall and between participants with and without diabetes were examined. Multiple linear regression was used to examine the influence of diabetes and changes in sedentary time during SET on functional and self-reported outcomes. Aim 3. A secondary analysis of data collected as part of Aim 2 was performed to determine the prevalence of nonresponse to SET in functional and quality of life outcomes using different methods of defining nonresponse reported in the literature. Inter- and intra-individual patterns of response were also examined. Results: Aim 1. A total of 17 articles representing 12 unique studies with 5116 unique participants were eligible for inclusion. Nonresponse to aerobic exercise interventions was prevalent among older adults (1.4-63.4%); age, sex, race, and body mass index were not found to be critical determinants of nonresponse, but there was some evidence to suggest that baseline fitness, health status, and exercise dose were important predictors of nonresponse. Aim 2. On average, sedentary time did not change following the 12-week SET program, although there was substantial inter-individual variability (40% decrease to a 38% increase in average daily minutes of sedentary time). While on average, participants with diabetes reduced their average daily sedentary time, participants without diabetes tended to increase their average sedentary time. In multiple linear regression, neither changes in sedentary time in the first six weeks of SET nor diabetes were significant predictors of changes in total distance attained on the six-minute walk test from baseline to 12 weeks. Aim 3. The prevalence of nonresponse in walking distance when defined as no change or a decline in walking distance was 35.3%, and when defined as the lack of a clinically meaningful improvement (20 meters), the prevalence of nonresponse was 55.9%. Similar patterns of response were observed in both the objective and self-reported measures of physical function. All participants improved in at least one study outcome; however only one participant improved in all measured outcomes. Conclusion: Nonresponse to a single study outcome following participation in aerobic exercise is a common phenomenon among older adults, both with and without PAD. Neither diabetes nor changes in sedentary time were significant predictors of response to SET among individuals with PAD. Exercise studies should include a variety of performance based and patient-reported outcomes, as nonresponse likely represents a failure in just one potential positive adaptation to exercise. Additional research should examine potentially modifiable predictors of response prior to the initiation of or during exercise training (e.g., motivation to exercise, social support), which would foster inquiry and efforts to modify and tailor programming to maximize an individual’s potential benefit from exercise therapy.