ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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- All Subjects: Biochemistry
- Creators: Sweazea, Karen
Description
While exercising mammalian muscle increasingly relies on carbohydrates for fuel as aerobic exercise intensity rises above the moderate range, flying birds are extraordinary endurance athletes and fuel flight, a moderate-high intensity exercise, almost exclusively with lipid. In addition, Aves have long lifespans compared to weight-matched mammals. As skeletal muscle mitochondria account for the majority of oxygen consumption during aerobic exercise, the primary goal was to investigate differences in isolated muscle mitochondria between these species and to examine to what extent factors intrinsic to mitochondria may account for the behavior observed in the intact tissue and whole organism. First, maximal enzyme activities were assessed in sparrow and rat mitochondria. Citrate synthase and aspartate aminotransferase activity were higher in sparrow compared to rat mitochondria, while glutamate dehydrogenase activity was lower. Sparrow mitochondrial NAD-linked isocitrate dehydrogenase activity was dependent on phosphate, unlike the mammalian enzyme. Next, the rate of oxygen consumption (JO), electron transport chain (ETC) activity, and reactive oxygen species (ROS) production were assessed in intact mitochondria. Maximal rates of fat oxidation were lower than for carbohydrate in rat but not sparrow mitochondria. ETC activity was higher in sparrows, but no differences were found in ROS production between species. Finally, fuel selection and control of respiration at three rates between rest and maximum were assessed. Mitochondrial fuel oxidation and selection mirrored that of the whole body; in rat mitochondria the reliance on carbohydrate increased as the rate of oxygen consumption increased, whereas fat dominated under all conditions in the sparrow. These data indicate fuel selection, at least in part, can be modulated at the level of the mitochondrial matrix when multiple substrates are present at saturating levels. As an increase in matrix oxidation-reduction potential has been linked to a suppression of fat oxidation and high ROS production, the high ETC activity relative to dehydrogenase activity in avian compared to mammalian mitochondria may result in lower matrix oxidation-reduction potential, allowing fatty acid oxidation to proceed while also resulting in low ROS production in vivo.
ContributorsKuzmiak, Sarah (Author) / Willis, Wayne T (Thesis advisor) / Mandarino, Lawrence (Committee member) / Sweazea, Karen (Committee member) / Harrison, Jon (Committee member) / Gadau, Juergen (Committee member) / Arizona State University (Publisher)
Created2012
Description
Diabetes is the 7th leading cause of death globally. In 2018, 34.2 million Americans had type 2 diabetes. Many symptoms of diabetes are similar to those of scurvy or vitamin C deficiency. Vitamin C marginality and inadequacy are more prevalent in Type 2 Diabetes/prediabetes than with normal glucose tolerance. Intracellular vitamin C inadequacy is suspected due to competition between dehydroascorbic acid and glucose at GLUT 1 and 3 cellular receptors. Erythrocyte osmotic fragility is noted in Gulo -/- knockout mice unable to synthesize endogenous vitamin C. The ascorbate deficient red blood cells presented with low cytoskeletal B-spectrin, spherocyte appearance, and impaired deformability. This cross-sectional study investigated the relationships between diabetes status, erythrocyte osmotic fragility, and serum vitamin C status. Participants were aged 18-65, non-smoking, reported no unresolved health complications, and denied prior vitamin C supplementation. Those with T2D indicated diagnosis of >1 year. All participants provided written informed consent and the study was approved by the local Institutional Review Board in January 2021. Participants provided one fasted blood sample. Erythrocyte osmotic fragility was measured via UV/Vis spectrophotometry with various concentrations of sodium chloride (0.85% - 0.10%) to induce osmotic stress. In addition, plasma was extracted and mixed 1:1 with 10% (w/v) metaphosphoric acid in 2 mmol/L disodium EDTA and centrifuged. The supernatant was stored at -80°C until analysis with isocratic reverse-phase UV-HPLC separation.
Participant characteristics did not differ significantly between groups apart from age (p< 0.01) and HbA1c (p=0.002). Data are presented for adults with T2D (n=14; 36% female; 55.5±8.2 y; 31.5±9.0 kg/m2; HbA1c: 7.4±1.9%; plasma vitamin C: 36.0±12.2 uM) and without T2D (n=16; 69% female; 38.7±13.5 y; 26.8±6.6 kg/m2; A1c: 5.4±0.3%; plasma vitamin C: 34.8±10.9uM). Erythrocyte osmotic fragility was significantly elevated (+4.4% hemolysis) in adults without T2D at 0.35% saline (p=0.039). Greater VC status (>30 uM) was associated with lower hemolysis at 0.35% NaCl (p=0.031). Erythrocyte osmotic stability was linked to greater vitamin C intake at 0.20% saline in those without T2D (p =0.019).
In this pilot study, vitamin C status did not differ significantly by diabetes status. Vitamin C status was directly linked to erythrocyte osmotic stability in adults without T2D.
ContributorsLundy, Ciara Cheyanne (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Alexon, Christy (Committee member) / Arizona State University (Publisher)
Created2022
Description
Chronic low-grade inflammation is a main pathogenic link between obesity and Type 2 Diabetes (T2D) and a putative target for treatment. While a wide array of pharmacologic agents is available to manage T2D, many patients still face perturbed glycemia and subclinical inflammation. Therefore, complementary nutraceutical strategies that target inflammation, metabolism, and resolution physiology hold promise as adjunctive options to quell the disturbed immuno-metabolic milieu observed in T2D. Omega-3 polyunsaturated fatty acids (PUFAs) and anthocyanins are two dietary components evidenced to mitigate inflammation and improve T2D risk factors, through distinct and similar targets. However, the combined use of such nutraceuticals has not yet been examined in individuals with T2D. This dissertation leveraged data from a larger randomized, double-blind, placebo-controlled trial conducted between January 2022—September 2023 investigating the use of combined supplementation (active treatment; [FOM]) of anthocyanins (600 mg/d maqui berry extract) and omega-3 PUFAs (3 g/day fish oil; 2 g/d EPA, 1 g/d DHA) for 8 weeks on cytokines and mental acuity in individuals with T2D, compared to a placebo (CON). The current study examined the effects of this supplemental strategy on markers of metabolic inflammation, oxidative stress, and cardiometabolic risk. The results indicated that a marker of sustained omega-3 dietary intake and tissue accumulation termed the Omega-3 Index was inversely associated with HbA1c (? = -8.5, 95%CI -15.1, -1.4, p = 0.022) and glucose (? = -12.4, 95%CI -22.9, -0.5, p = 0.042), after adjustment for covariates at baseline across all participants with T2D in this study. However, outcomes from linear mixed model analyses demonstrated that there were no significant differences in change from baseline between FOM and CON groups at week 8 in any of the inflammatory, oxidative stress, glycemic control, or circulating lipid markers assessed in this study. These null effects were observed despite a 93% greater increase from baseline in the Omega-3 Index observed in the FOM group compared to the CON group at week 8. Therefore, the findings do not support significant treatment effects associated with 2 months of combined marine omega-3 PUFAs and maqui berry extract on inflammatory and cardiometabolic outcomes in individuals with T2D.
ContributorsFessler, Samantha Nicole (Author) / Johnston, Carol S (Thesis advisor) / Sweazea, Karen (Committee member) / Wang, Shu (Committee member) / Kavouras, Stavros A (Committee member) / Grimm, Kevin J (Committee member) / Arizona State University (Publisher)
Created2024