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- All Subjects: Physiology
- Creators: Sweazea, Karen
- Creators: Sweazea, Karen L
- Status: Published
Description
ABSTRACT The hormone leptin is an important regulator of body weight and energy balance, while nitric oxide (NO) produced in the blood vessels is beneficial for preventing disease-induced impaired vasodilation and hypertension. Elevations in the free radical superoxide can result in impaired vasodilation through scavenging of NO. Omega 3 is a polyunsaturated fatty acid that is beneficial at reducing body weight and in lowering many cardiovascular risk factors like atherosclerosis. The present study was designed to examine the change in plasma concentrations of leptin, nitric oxide, and the antioxidant superoxide dismutase in addition to examining the association between leptin and NO in healthy normal weight adult female subjects before and following omega 3 intakes. Participants were randomly assigned to either a fish oil group (600 mg per day) or a control group (1000 mg of coconut oil per day) for 8 weeks. Results showed no significant difference in the percent change of leptin over the 8 week supplementation period for either group (15.3±31.9 for fish oil group, 7.83±27 for control group; p=0.763). The percent change in NO was similarly not significantly altered in either group (-1.97±22 decline in fish oil group, 11.8±53.9 in control group; p=0.960). Likewise, the percent change in superoxide dismutase for each group was not significant following 8 weeks of supplementation (fish oil group: 11.94±20.94; control group: 11.8±53.9; p=0.362). The Pearson correlation co-efficient comparing the percent change of both leptin and NO was r2= -0.251 demonstrating a mildly negative, albeit insignificant, relationship between these factors. Together, these findings suggest that daily supplementation with 600 mg omega 3 in healthy females is not beneficial for improving these cardiovascular risk markers. Future studies in this area should include male subjects as well as overweight subjects with larger doses of fish oil that are equivalent to three or more servings per week. The importance of gender cannot be underestimated since estrogen has protective effects in the vasculature of females that may have masked any further protective effects of the fish oil. In addition, overweight individuals are often leptin-resistant and develop impaired vasodilation resulting from superoxide-mediated scavenging of nitric oxide. Therefore, the reported antioxidant and weight loss properties of omega 3 supplementation may greatly benefit overweight individuals.
ContributorsAlanbagy, Samer (Author) / Sweazea, Karen (Thesis advisor) / Johnston, Carol (Committee member) / Shepard, Christina (Committee member) / Lespron, Christy (Committee member) / Arizona State University (Publisher)
Created2014
Description
Long term high fat diets (HFD) are correlated with the development of diabetes
and kidney disease. However, the impact of short term high fat intake on the etiology of kidney disease has not been well-studied. Therefore, this study examined the impact of a six week HFD (60% fat) on kidney structure and function in young male Sprague-Dawley rats. Previous studies have shown that these animals develop indices of diabetes compared to rats fed a standard rodent chow (5% fat) for six weeks. The hypothesis of this study is that six weeks of HFD will lead to early stages of kidney disease as evidenced by morphological and functional changes in the kidney. Alterations in morphology were determined by measuring structural changes in the kidneys (changes in mass, fatty acid infiltration, and structural damage). Alterations in kidney function were measured by analyzing urinary biomarkers of oxidative RNA/DNA damage, renal tissue lipid peroxidation, urinary markers of impaired kidney function (urinary protein, creatinine, and hydrogen peroxide (H2O2)), markers of inflammation (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6)), as well as cystatin C, a plasma biomarker of kidney function. The results of these studies determined that short term HFD intake is not sufficient to induce early stage kidney disease. Beyond increases in renal mass, there were no significant differences between the markers of renal structure and function in the HFD and standard rodent chow-fed rats.
and kidney disease. However, the impact of short term high fat intake on the etiology of kidney disease has not been well-studied. Therefore, this study examined the impact of a six week HFD (60% fat) on kidney structure and function in young male Sprague-Dawley rats. Previous studies have shown that these animals develop indices of diabetes compared to rats fed a standard rodent chow (5% fat) for six weeks. The hypothesis of this study is that six weeks of HFD will lead to early stages of kidney disease as evidenced by morphological and functional changes in the kidney. Alterations in morphology were determined by measuring structural changes in the kidneys (changes in mass, fatty acid infiltration, and structural damage). Alterations in kidney function were measured by analyzing urinary biomarkers of oxidative RNA/DNA damage, renal tissue lipid peroxidation, urinary markers of impaired kidney function (urinary protein, creatinine, and hydrogen peroxide (H2O2)), markers of inflammation (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6)), as well as cystatin C, a plasma biomarker of kidney function. The results of these studies determined that short term HFD intake is not sufficient to induce early stage kidney disease. Beyond increases in renal mass, there were no significant differences between the markers of renal structure and function in the HFD and standard rodent chow-fed rats.
ContributorsCrinigan, Catherine (Author) / Sweazea, Karen (Thesis advisor) / Johnston, Carol (Committee member) / Mayol-Kreiser, Sandra (Committee member) / Arizona State University (Publisher)
Created2015
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
Birds have plasma glucose levels that are 1.5-2 times greater than mammals of similar body mass in addition to higher free fatty acid concentrations, both of which would typically impair endothelium-dependent vasodilation if observed in mammals. Endothelium-dependent vasodilation can be stimulated in mammals through the use of acetylcholine (ACh), which primarily acts through nitric oxide (NO) and cyclooxygenase (COX)-mediated pathways, with varying reliance on endothelial-derived hyperpolarizing factors (EDHFs). Very few studies have been conducted on small resistance systemic arteries from birds. The hypothesis was that because birds have naturally high glucose and free fatty acid concentrations, ACh-induced vasodilation of isolated arteries from mourning doves (Zenaida macroura) would be independent of endothelial-derived factors and resistant to high glucose-mediated vascular dysfunction. Small resistance mesenteric and cranial tibial (c. tibial) arteries were pre-constricted to 50% of resting inner diameter with phenyleprine then exposed to increasing doses of ACh (10-9 to 10-5 μM) or the NO donor, sodium nitroprusside (SNP; 10-12 to 10-3 μM). For both vessel beds, ACh-induced vasodilation occurred mainly through the activation of potassium channels, whereas vasodilation of mesenteric arteries additionally occurred through COX. Although arteries from both vessel beds fully dilated with exposure to sodium nitroprusside, ACh-mediated vasodilation was independent of NO. To examine the effect of high glucose on endothelium-dependent vasodilation, ACh dose response curves were conducted following exposure of isolated c. tibial arteries to either a control solution (20mM glucose) or high glucose (30mM). ACh-induced vasodilation was significantly impaired (p = 0.013) when exposed to high glucose, but normalized in subsequent vessels with pre-exposure to the superoxide dismutase mimetic tiron (10 mM). Superoxide concentrations were likewise significantly increased (p = 0.0072) following exposure to high glucose. These findings indicate that dove arteries do not appear to have endogenous mechanisms to counteract the deleterious effects of oxidative stress. Additional studies are required to assess whether endogenous mechanisms exist to protect avian vascular reactivity from systemic hyperglycemia.
ContributorsJarrett, Catherine Lee (Author) / Sweazea, Karen L (Thesis advisor) / Johnston, Carol (Committee member) / Gaesser, Glenn (Committee member) / Arizona State University (Publisher)
Created2012
Description
The ability to tolerate bouts of oxygen deprivation varies tremendously across the animal kingdom. Adult humans from different regions show large variation in tolerance to hypoxia; additionally, it is widely known that neonatal mammals are much more tolerant to anoxia than their adult counterparts, including in humans. Drosophila melanogaster are very anoxia-tolerant relative to mammals, with adults able to survive 12 h of anoxia, and represent a well-suited model for studying anoxia tolerance. Drosophila live in rotting, fermenting media and a result are more likely to experience environmental hypoxia; therefore, they could be expected to be more tolerant of anoxia than adults. However, adults have the capacity to survive anoxic exposure times ~8 times longer than larvae. This dissertation focuses on understanding the mechanisms responsible for variation in survival from anoxic exposure in the genetic model organism, Drosophila melanogaster, focused in particular on effects of developmental stage (larval vs. adults) and within-population variation among individuals.
Vertebrate studies suggest that surviving anoxia requires the maintenance of ATP despite the loss of aerobic metabolism in a manner that prevents a disruption of ionic homeostasis. Instead, the abilities to maintain a hypometabolic state with low ATP and tolerate large disturbances in ionic status appear to contribute to the higher anoxia tolerance of adults. Furthermore, metabolomics experiments support this notion by showing that larvae had higher metabolic rates during the initial 30 min of anoxia and that protective metabolites were upregulated in adults but not larvae. Lastly, I investigated the genetic variation in anoxia tolerance using a genome wide association study (GWAS) to identify target genes associated with anoxia tolerance. Results from the GWAS also suggest mechanisms related to protection from ionic and oxidative stress, in addition to a protective role for immune function.
Vertebrate studies suggest that surviving anoxia requires the maintenance of ATP despite the loss of aerobic metabolism in a manner that prevents a disruption of ionic homeostasis. Instead, the abilities to maintain a hypometabolic state with low ATP and tolerate large disturbances in ionic status appear to contribute to the higher anoxia tolerance of adults. Furthermore, metabolomics experiments support this notion by showing that larvae had higher metabolic rates during the initial 30 min of anoxia and that protective metabolites were upregulated in adults but not larvae. Lastly, I investigated the genetic variation in anoxia tolerance using a genome wide association study (GWAS) to identify target genes associated with anoxia tolerance. Results from the GWAS also suggest mechanisms related to protection from ionic and oxidative stress, in addition to a protective role for immune function.
ContributorsCampbell, Jacob B (Author) / Harrison, Jon F. (Thesis advisor) / Gadau, Juergen (Committee member) / Call, Gerald B (Committee member) / Sweazea, Karen L (Committee member) / Rosenberg, Michael S. (Committee member) / Arizona State University (Publisher)
Created2018
Description
Reproduction is energetically costly and seasonal breeding has evolved to capitalize on predictable increases in food availability. The synchronization of breeding with periods of peak food availability is especially important for small birds, most of which do not store an extensive amount of energy. The annual change in photoperiod is the primary environmental cue regulating reproductive development, but must be integrated with supplementary cues relating to local energetic conditions. Photoperiodic regulation of the reproductive neuroendocrine system is well described in seasonally breeding birds, but the mechanisms that these animals use to integrate supplementary cues remain unclear. I hypothesized that (a) environmental cues that negatively affect energy balance inhibit reproductive development by acting at multiple levels along the reproductive endocrine axis including the hypothalamus (b) that the availability of metabolic fuels conveys alterations in energy balance to the reproductive system. I investigated these hypotheses in male house finches, Haemorhous mexicanus, caught in the wild and brought into captivity. I first experimentally reduced body condition through food restriction and found that gonadal development and function are inhibited and these changes are associated with changes in hypothalamic gonadotropin-releasing hormone (GnRH). I then investigated this neuroendocrine integration and found that finches maintain reproductive flexibility through modifying the release of accumulated GnRH stores in response to energetic conditions. Lastly, I investigated the role of metabolic fuels in coordinating reproductive responses under two different models of negative energy balance, decreased energy intake (food restriction) and increased energy expenditure (high temperatures). Exposure to high temperatures lowered body condition and reduced food intake. Reproductive development was inhibited under both energy challenges, and occurred with decreased gonadal gene expression of enzymes involved in steroid synthesis. Minor changes in fuel utilization occurred under food restriction but not high temperatures. My results support the hypothesis that negative energy balance inhibits reproductive development through multilevel effects on the hypothalamus and gonads. These studies are among the first to demonstrate a negative effect of high temperatures on reproductive development in a wild bird. Overall, the above findings provide important foundations for investigations into adaptive responses of breeding in energetically variable environments.
ContributorsValle, Shelley (Author) / Deviche, Pierre (Thesis advisor) / McGraw, Kevin (Committee member) / Orchinik, Miles (Committee member) / Propper, Catherine (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2018
Description
The prevalence of obesity and obesity-related disorders have increased world-wide. In the last decade, the intestinal microbiome has become a major indicator of metabolic and gastrointestinal health. Previous research has shown that high-fat diet (HFD) consumption can alter the microbial composition of the gut by increasing the abundance of gram-positive bacteria associated with the onset of obesity and type 2 diabetes. Although, the most common form of obesity and metabolic syndrome intervention is exercise and diet, these recommendations may not improve severe cases of obesity. Thus, an important relevance of my project was to investigate whether the intake of an organometallic complex (OMC) would prevent the onset of metabolic and gastrointestinal complications associated with high-fat diet intake. I hypothesized that the consumption of a HFD for 6 weeks would promote the development of metabolic and gastrointestinal disease risk factors. Next, it was hypothesized that OMC treatment would decrease metabolic risk factors by improving insulin sensitivity and decreasing weight gain. Finally, I hypothesized that HFD-intake would increase the abundance of gram-positive bacteria associated with gastrointestinal disease. My preliminary data investigated the effects of a 6-week HFD on the development of hepatic steatosis, intestinal permeability and inflammation in male Sprague Dawley rats. I found that a 6-week HFD increases hepatic triglyceride concentrations, plasma endotoxins and promotes the production of pro-inflammatory cytokines in the cecum wall. I then investigated whether OMC treatment could prevent metabolic risk factors in male Sprague-Dawley rats fed a HFD for 10 weeks and found that OMC can mitigate risk factors such hyperglycemia, liver disease, impaired endothelial function, and inflammation. Lastly, I investigated the effects of a 10-week HFD on the gastrointestinal system and found an increase in liver triglycerides and free glycerol and alterations of the distal gut microbiome. My results support the hypothesis that a HFD can promote metabolic risk factors, alter the gut microbiome and increase systemic inflammation and that OMC treatment may help mitigate some of these effects. Together, these studies are among the first to demonstrate the effects of a soil-derived compound on metabolic complications. Additionally, these conclusions also provide an essential basis for future gastrointestinal and microbiome studies of OMC treatment.
ContributorsCrawford, Meli'sa Shaunte (Author) / Sweazea, Karen L (Thesis advisor) / Deviche, Pierre (Thesis advisor) / Al-Nakkash, Layla (Committee member) / Whisner, Corrie (Committee member) / Hyatt, Jon-Philippe (Committee member) / Arizona State University (Publisher)
Created2019
Description
Birds have unusually high plasma glucose concentrations compared to mammals of similar size despite their high metabolic rate. While birds use lipids as their main source of energy, it is still unclear how and why they maintain high plasma glucose concentrations. To investigate a potential underlying mechanism, this study looks at the role of lipolysis in glucose homeostasis. The purpose of this study is to examine the effects of decreased glycerol availability (through inhibition of lipolysis) on plasma glucose concentrations in mourning doves. The hypothesis is that decreased availability of glycerol will result in decreased production of glucose through gluconeogenesis leading to reduced plasma glucose concentrations. In the morning of each experiment, mourning doves were collected at the Arizona State University Tempe campus, and randomized into either a control group (0.9% saline) or experimental group (acipimox, 50mg/kg BM). Blood samples were collected prior to treatment, and at 1, 2, and 3 hours post-treatment. At 3 hours, doves were euthanized, and tissue samples were collected for analysis. Acipimox treatment resulted in significant increases in blood glucose concentrations at 1 and 2 hours post- treatment as well as renal triglyceride concentrations at 3 hours post-treatment. Change in plasma free glycerol between 0h and 3h followed an increasing trend for the acipimox treated animals, and a decreasing trend in the saline treated animals. These results do not support the hypothesis that inhibition of lipolysis should decrease blood glycerol and blood glucose levels. Rather, the effects of acipimox in glucose homeostasis appear to differ significantly between birds and mammals suggesting differing mechanisms for glucose homeostasis.
ContributorsKouteib, Soukaina (Author) / Sweazea, Karen (Thesis director) / Deviche, Pierre (Committee member) / Chandler, Douglas (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.
ContributorsO'Neill, Liam Martin (Author) / Sweazea, Karen (Thesis director) / Angadi, Siddhartha (Committee member) / Dickinson, Jared (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Background: Despite the reported improvements in glucose regulation associated with flaxseeds (Linum usitatissimum) few clinical trials have been conducted in diabetic participants. Objective: To evaluate the efficacy of ground flaxseed consumption at attenuating hyperglycemia, dyslipidemia, inflammation, and oxidative stress as compared to a control in adults with non-insulin dependent type 2 diabetes (T2D). Design: In a randomized parallel arm controlled efficacy trial, participants were asked to consume either 28 g/d ground flaxseed or the fiber-matched control (9 g/d ground psyllium husk) for 8 weeks. The study included 17 adults (9 male, 8 females; 46±14 y; BMI: 31.4±5.7 kg/m2) with a diagnosis of T2D ≥ 6 months. Main outcomes measured included: glycemic control (HbA1c, fasting plasma glucose, fasting serum insulin, and HOMA-IR), lipid profile (total cholesterol, LDL-C, HDL-C, total triglycerides, and calculated VLDL-C), markers of inflammation and oxidative stress (TNF-alpha, TBARS, and NOx), and dietary intake (energy, total fat, total fiber, sodium). Absolute net change for measured variables (week 8 values minus baseline values) were compared using Mann-Whitney U non-parametric tests, significance was determined at p ≤ 0.05. Results: There were no significant changes between groups from baseline to week 8 in any outcome measure of nutrient intake, body composition, glucose control, or lipid concentrations. There was a modest decrease in TNF-alpha in the flaxseed group as compared to the control (p = 0.06) as well as a mild decrease in TBARS in the flaxseed as compared to the control group (p = 0.083), though neither were significant. Conclusions: The current study did not detect a measurable association between 28 g/d flaxseed consumption for 8 weeks in T2D participants and improvements in glycemic control or lipid profiles. There was a modest, albeit insignificant, decrease in markers of inflammation and oxidative stress in the flaxseed group as compared to the control, which warrants further study.
ContributorsRicklefs, Kristin (Author) / Sweazea, Karen L (Thesis advisor) / Johnston, Carol S (Committee member) / Gaesser, Glenn (Committee member) / Vega-Lopez, Sonia (Committee member) / Gonzales, Rayna (Committee member) / Arizona State University (Publisher)
Created2015