Medicine and Health Sciences Commons^™

The Effect Of Estrogen And A Mitochondrial Uncoupling Prodrug On Traumatic Brain Injury-Induced Dysfunction In Mice., Olivia J. Kalimon

Theses and Dissertations--Neuroscience

A large percent of both clinical and pre-clinical traumatic brain injury (TBI) studies report better outcomes females after severe injury compared to males. Mitochondrial dysfunction is a well-characterized driver of secondary injury and an attractive neurotherapeutic target; though, there is limited research available on mitochondrial dysfunction in females. However, a few studies have shown total mitochondria from the cortex of females appear protected from TBI-induced bioenergetic dysfunction. These results were replicated in these studies so further characterization was performed. Additionally, protein expression of some oxidative phosphorylation (OXPHOS) complexes were elevated in the uninjured cortex of females relative to uninjured males, …

Ethanol Dysregulates Sirt1-Mediated Lipogenic Signaling Pathways Through Α4*-Nicotinic Acetylcholine Receptors In Hepatocytes., Caitlin Christina Wilkerson

Electronic Theses and Dissertations

Alcohol-associated liver disease (ALD) is a broad spectrum of diseases ranging from steatosis to severe hepatic cirrhosis, none of which have any FDA approved therapies. Downregulation of hepatic Sirtuin 1 (Sirt1) activity by ethanol has been shown to lead to an upregulation of the pro-lipogenic gene targets under its jurisdiction, resulting in increased lipogenesis and triglyceride accumulation. It was hypothesized that ethanol acts on α4*-nicotinic acetylcholine receptors (α4*-nAChRs) in hepatocytes to decrease Sirt1 expression, which ultimately dysregulates lipid metabolic homeostasis. Ethanol’s effects were investigated in cultured AML12 hepatocytes and in WT primary mouse hepatocytes acutely exposed to ethanol. Consistent with …

Investigation Of Heterocyclic Amines And N-Acetyltransferase 2 Genetic Polymorphism In The Dysregulation Of Hepatic Energy Homeostasis: A Gene-Environment Approach., Kennedy M Walls

Electronic Theses and Dissertations

Heterocyclic amines (HCAs) are mutagens generated when cooking meat for prolonged periods of time or until well-done. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes. However, no previous studies have examined if HCAs, independent of meat consumption, contributes to pathogenesis of insulin resistance or metabolic disease. It is well known that HCAs require hepatic bioactivation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans that, depending on the combination of NAT2 alleles, correlate to rapid, intermediate, or slow acetylator phenotypes that exhibit differential …

Investigating The Effects Of Subchronic Dietary Zinc Supplementation On Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease., Oluwanifemi Esther Bolatimi

Electronic Theses and Dissertations

Zinc deficiency is associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Previous studies show zinc supplementation improves steatosis, but its therapeutic effects in established MASLD remain unclear. We developed a model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced MASLD and hypothesized established MASLD would be attenuated. Mice were fed control diet or HFD for 12 weeks and then grouped into normal or zinc-supplemented diets for 8 additional weeks. At euthanasia, plasma and liver tissues were collected for phenotypic analysis. Twelve weeks of HFD altered glucose clearance and body composition. Eight weeks of subsequent zinc supplementation …

Chronic Stressors, Obesity Pathogenesis, And The Moderating Effect Of Internalized Weight Stigma; A Quantitative, Illinois Study, Karyn Byrne

Dissertations

The obesity epidemic is a ‘wicked’ problem with a complex web of determinants and outcomes. While generally higher for minoritized populations, prevalence rates manifest in surprising, nonlinear patterns. There is no consensus regarding treatment protocols or mitigation efforts, except that current efforts remain largely ineffective. Much research evidence that a profusion of determinants of health support obesity pathogenesis through various physiological processes and mechanisms, including the allostatic load, mitochondria functioning, the gut microbiome, and epigenetics. Intervening to support markers of the allostatic load (immunity, inflammation, and metabolic health) may provide a more effective treatment outcomes than traditional approaches, which tend …

The Combined Effects Of Physical Exercise And Cognitive Training On Gait Speed And Primary Motor Cortex Metabolism In Individuals With Mild Cognitive Impairment: A 1h-Mrs Analysis, Jack Thomas Emsey Elkas

Electronic Thesis and Dissertation Repository

Mild cognitive impairment (MCI) is a transitional stage before dementia. Altered gait in MCI has been associated with progression to dementia. Using magnetic resonance spectroscopy, a relationship between primary motor cortex (M1) neurochemistry and dual task gait speed has been reported in MCI. Interventional research suggests exercise, cognitive training, and vitamin D supplementation may benefit MCI, yet the combined effect of these treatments on gait speed and M1 metabolism is unknown. Participants with MCI (N=75) were assigned to one of five intervention arms and dual task cost on gait speed and M1 metabolism was assessed before and five months after …

Effect Of Acute Exercise On Muscle And Liver Glucose Metabolism In T1dm Rodents, Justin A. Camenzuli

Electronic Thesis and Dissertation Repository

Individuals with Type I Diabetes Mellitus (T1DM) are at an increased risk for developing secondary complications which increases their risk of premature death. While the risk of secondary complications is reduced with intensive insulin treatment (IIT) and aerobic exercise (AE), both interventional strategies increase the risk of hypoglycemia. This study examined the effects of a 60-min bout of forced treadmill AE on hepatic and muscular blood glucose (BG) metabolism. Nineteen Sprague-Dawley rats were divided into two groups: Sedentary Control Rats (SC; n=5), and Sedentary T1DM rats (DSC); T1DM rats were subcategorized into Diabetic Pre-Exercise (DPRE; n=14) and Diabetic Post-Exercise (DPOST; …

Utilizing Ultra-Performance Chromatography High-Resolution Mass Spectrometry To Investigate Fatty Acid Mediated Antibiotic Tolerance, Brittni Woodall

Doctoral Dissertations

The lipid membrane is the first component necessary to sustain life. To maintain homeostasis, segregate cellular machinery, provide protection from the environment, and reproduce, an organism must establish a boundary in which the processes can occur. Throughout the last two decades, research has propelled our knowledge of lipid membranes much beyond original hypotheses. Once thought of to be static and uniform, the understanding of the lipid membrane has evolved to encompass a structure that is responsive, unique, and intricately constructed by the organism itself. By chance or by choice, organisms adapt the lipid membrane according to the environment for which …

Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters

Undergraduate Honors Theses

Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD⁺) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD⁺ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPR^mt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD⁺ and through increasing levels …

Differential Transcriptional Alterations In Detoxification Genes In Parkinson’S Disease In Egypt, Nourhan Shebl

Theses and Dissertations

PD is the most common motor neurodegenerative disease worldwide. The underlying cause of PD is still unknow, owingthis to the complexity of the disease. Often, genetics and environmental factors are collaborating in the initiation of the disease. Despite the diversity of its genetical and environmental profiles, the Egyptian population is one of the mostunderrepresented population in terms of PD research. In this study, we investigated PD through various perspectives tohighlight the complexity of the disease in Egypt, taking into consideration the diversity of the Egyptian population. We recruited PD patients and reference controls from 4 governorates: Cairo, Giza, Alexandria, and …

Adolescence, Alcohol, And Astrocytes: The Impact Of Adolescent Alcohol Use On Astrocyte-Synaptic Interactions, Structure, Function, And Behavior, Christopher Douglas Walker

Theses, Dissertations and Capstones

Alcohol is the third leading cause of preventable death in the United States and has substantial social and economic burdens. Excessive alcohol consumption in the form of binge drinking is highly prevalent among adolescents and emerging adults. Binge drinking is a form of excessive drinking, defined as consuming enough alcohol on a single occasion to result in blood alcohol concentrations above 0.08%. Approximately 55% of full-time college students aged 18- 22 years old have reported consuming alcohol in a binge manner. Furthermore, studies have shown that approximately 20% of college students meet the criteria for an alcohol use disorder (AUD). …

Support Their Sleep: Enhancing Nurses' Knowledge And Implementation Of Non-Pharmacological Sleep Protocols To Improve Patient Rest, Recovery, And Reduce Cognitive Impairment., David C. Barry

Master's Theses and Capstones

Background: Sleep and rest play an influential role in promoting recovery and healing in humans. Hospitalized patients are at risk for altered sleep from hospitalization, illness, and stimulation from a hospital environment. Non-pharmacologic interventions preformed by nurses can help to improve sleep and sleep environment for patients.

Local problem: There was no protocol or available information regarding patient sleep promotion for nurses to references when caring for patients.

Methods: Nurses in the microsystem (n=8) were administered a pre/post questionnaire containing Likert scales and a short quiz containing knowledge-based questions. Questionnaires were distributed to nurses prior to and after …

Knockout Of Endospanin 1 Via Crispr In Zebrafish, Danio Rerio, Jared Kittinger

Williams Honors College, Honors Research Projects

I made endospanin 1 knockout (KO) zebrafish to examine its effects on lipid and bone metabolism. Endospanin 1, or leptin receptor overlapping transcript (leprot), is a cytosolic protein linked to the protein hormone leptin that influences the trafficking of leptin receptors to the plasma membrane of cells. Genes for endospanin and tyrosinase (a pigmentation enzyme) were targeted via a microinjection of guide RNAs and CRISPR Cas9 into zebrafish embryos at 2-4 cell stages. I was able to disrupt the endospanin 1 gene (based upon the disruption of tyrosinase), but very few mutant zebrafish fully developed into adults. Only low KO …

The Effects Of Sex On Zebrafish Bone Metabolism, Simon Bagatto

Williams Honors College, Honors Research Projects

I investigated the effects of diet and sex on zebrafish bone metabolism. Zebrafish were subjected to either a high-calorie or low-calorie diet over a five-week period. After this diet, zebrafish scales were used to measure alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) enzyme activity with a fluorescent substrate. The enzyme activities were markers of the osteoblasts (ALP) and the osteoclasts (TRAP). These data were compared among sex and diet of the zebrafish using a repeated measures ANOVA statistical test. I also measured the number of resorption lacunae per scale (another indicator of osteoclast activity). The results showed higher TRAP …

Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum

Electronic Theses and Dissertations

Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …

The Impact Of Single Nucleotide Polymorphisms On Cortisol Receptor Activity In Populations With Obesity, Cassidy Michalicka

Honors Theses

Cortisol is a crucial part of the endocrine system; it has the capacity to affect nearly every organ and tissue in the human body. When functioning correctly, cortisol is known to regulate the body’s stress response, control metabolism, suppress inflammation, regulate blood pressure, regulate blood sugar, regulate our body’s circadian rhythm, and much more. When the concentration of cortisol in the blood is elevated for an excessive period, the body responds with symptoms such as hyperglycemia, hypertension, weight gain, and moon face. Commonly this is known as Cushing’s Syndrome (CS), and interestingly, we have seen a phenotypic resemblance when contrasted …

Reno-Protective And Immune Effects Of Growth Differentiation Factor 15 In Obesity-Related Kidney Disease, Jessie T. Sullivan

Honors Thesis

According to the World Health Organization, worldwide obesity has tripled since 1975 and is still on the rise, putting people at a higher risk of some cardiovascular diseases and kidney disease. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied recently for its role in multiple biological processes and diseases. The member of the transforming growth factor beta (TGF-b) family has been investigated as a therapeutic agent and biomarker for obesity and associated cardiovascular diseases, stroke, diabetes, osteoarthritis, cancer, and kidney disease. Studies have shown the anti-inflammation, anti-obesity, and anti-diabetic effects of GDF15, but few have …

Regulation Of Pancreatic Cancer Progression By Micronutrients, Chunbo He

Theses & Dissertations

Cancer cells rely on altered metabolism to support their uncontrolled proliferation under harsh conditions. Understanding the mechanisms of how metabolic alterations support tumor growth may provide a way to enhance current therapies. Vitamins are micronutrients that our body needs in small quantities but are essential for health maintenance. A number of metabolic processes relevant to cancer initiation and progression are also regulated by vitamins. Here, our studies showed that pancreatic ductal adenocarcinoma (PDAC) cells display an aberrant metabolism of vitamin B6 (VB6) to support their fast proliferation. VB6 was highly demanded and rapidly metabolized by PDAC cells. Depletion of VB6 …

Characterizing The Roles Of Cannabinoid Receptor 1 & 2 In Zebrafish Behavior, Metabolism, And Seizure-Induced Activity, Kayci Kimmons

Honors Theses

Epileptic disorders like Dravet Syndrome require novel studies to determine the most ideal treatment. New research linking the endocannabinoid system (ECS) to epileptic disorders is arising, but there is still much to be discovered about the function and regulatory impact of the endocannabinoid system and its receptors in epilepsies like Dravet. In this study, knockout models of larval and adult zebrafish (Danio rerio) were used to investigate the roles of cannabinoid receptors 1 & 2 in behavior, brain mitochondrial metabolism, and seizure-induced activity following exposure to THC and CBD. Larval zebrafish which lacked cannabinoid receptor 1 exhibited increased …

Targeting Metabolic Adaptations To Anti-Angiogenic Therapy In Ovarian Cancer, Deanna M. Glassman, Deanna Glassman

Dissertations & Theses (Open Access)

ABSTRACT

Background: Ovarian cancer is the most lethal gynecologic malignancy. Despite modest clinical improvements with anti-VEGF antibody (AVA) therapy, adaptive resistance is nearly ubiquitous and additional therapeutic options are limited. A dependence on glutamine metabolism, via the enzyme glutaminase (GLS), is a known mechanism of adaptive resistance.

Purpose: To assess the efficacy of a glutaminase inhibitor as a means of exploiting the metabolic vulnerability of glutamine dependence that develops as a result of adaptive resistance to AVA therapy.

Experimental Design: We used a glutaminase inhibitor (GLSi) synthesized at MD Anderson Cancer Center for all in vitro and in vivo experiments. …

The Tca Cycle As A Nexus Of Metabolic Vulnerabilities In Cancer, Sunada Khadka

Dissertations & Theses (Open Access)

Uncontrolled proliferation of cancer cells necessitates rewiring of metabolic pathways to meet biosynthetic and bioenergetic demands of proliferation and fortify redox homeostasis. An increasing body of literature suggests that mitochondrial metabolism (tricarboxylic acid cycle (TCA) and oxidative phosphorylation) is imperative for cancer cell growth and proliferation. The scope of the works presented in this dissertation is to explore the importance of mitochondrial metabolism, and primarily the TCA cycle—the anabolic factory of cancer cells and leverage it as a targetable vulnerability in cancer. Cancer cells consume anabolic nutrients that are used to generate biosynthetic precursors in the TCA cycle. Continuous efflux …

Severe Hypoxia Up-Regulates Gluconeogenesis In Daphnia, Morad C. Malek

Undergraduate Honors Theses

Hypoxia is a significant low oxygen state that has complex and diverse impacts on organisms. In aerobes, various adaptive responses to hypoxia are observed that vary depending on the level of oxygen depletion and previous adaptation, hence the continued attention to hypoxia as an important abiotic stressor. Adaptive responses to hypoxia are primarily governed by the hypoxia-inducible factors (HIFs), which activate downstream genetic pathways responsible for oxygen transport and metabolic plasticity. In aquatic habitats, oxygen availability can vary greatly over time and space. Therefore, aquatic organisms’ adaptation to hypoxia is likely pervasive, especially in genotypes originating from waterbodies prone to …

Nutritional Status In Critical Care Of Covid-19 Patients, Dolph Lewis Davis Iii

Theses and Dissertations--Nutrition and Food Systems

Critical care nutrition is a poorly researched, and such a sudden pandemic event requiring manipulation of nutritional status via propofol-induced sedation for mechanical ventilation is potentially impactful on patient outcomes. This paper seeks to provide context to the impact of critical care protocols on the nutritional status of obese patients suffering from COVID-19.

Examining The Effects Of Exercise-Induced, Physical Stress Overtraining On Stress Biomarkers In Adolescent, C57bl/6 Mice, Curtis Scotty Davis

Theses, Dissertations and Capstones

Exercise has long been established as a therapeutic modality to improve health and related physical fitness, sports performance, and injury/risk reduction in both adults and adolescents (Haff & Triplett, 2015; Kaminsky, 2010). Nonetheless, there is a lack of research investigating the negative effects of exercise overstress (i.e., overtraining syndrome) in these populations, particularly adolescents (Brenner & American Academy of Pediatrics Council on Sports Medicine and Fitness, 2007; Matos & Winsley, 2007). The objective of this study was to examine hormone biochemical markers, anthropometric markers, and behavioral traits, which are associated with overtraining syndrome, in adolescent C57BL/6 mice. A total of …

Deletion Of Period Genes Exacerbates Diet-Induced Obesity In Female, But Not Male, Mice, Elizabeth Kantra

Theses and Dissertations--Biology

Sex differences in obesity in mice are mediated by differential responses of circadian rhythms to high-fat feeding in males and females. Other studies also showed circadian Period genes regulate diet-induced obesity in mice. In this study, we investigated the role of the Period genes in regulating sex differences in obesity. Male and female C57BL/6J wild type, Per1/2 KO, and Per1/2/3 KO mice were housed in 12L:12D and fed high-fat diet for 12 weeks. We found a striking sex difference in obesity such that disabling the Period genes exacerbated adiposity in female, but not male, mice. Increased adiposity in female Period …

Macronutrient Intake: A Multi-Sport Study Of Female Division I Collegiate Athletes, Ffion Price

Theses and Dissertations

Background: Macronutrients play a critical role within collegiate athletes’ performance and health, with carbohydrates providing most of the energy needs for most athletes. There is little research examining the macronutrient intake of healthy collegiate female athletes across sports. The aim of the present study was to compare macronutrient intakes of female collegiate athletes within different sports and compare their intakes to recommendations. Methods: An observational study was conducted to determine whether a sample of female collegiate athletes (n=26) consumed the IOC nutritional recommendations. Sports included within the study were soccer, basketball, volleyball, and cross-country. Athletes were asked to complete a …

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

MSU Graduate Theses

Recent insights into the pathological role of Nucleotide P2Y₂ receptor suggest P2Y₂R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y₂R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y₂R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y₂ in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …

The Associations Of Chronic Stress, Social Support, Health Behaviors And Metabolic Syndrome Among Hispanic Women, Edna Esquer

Dissertations

The Associations of Chronic Stress, Social Support, Health Behaviors and Metabolic Syndrome Among Hispanic Women

Background: Metabolic syndrome (MetS) prevalence is 25% among Mexican American women 30 – 49 years of age, compared to 22% among non-Hispanic Whites in the United States. Little is known about the additional contributions of chronic stress, social support and health behaviors to the development of MetS among this population.

Purpose: Describe the associations between chronic stress, social support, and health behaviors and the presence of MetS in Hispanic women living in an underserved community.

Methods: A retrospective cohort study design. The Adult Treatment Panel …

Fucoxanthin: A Review Of Potential Benefits Relative To Human Health, Michael R. White

Masters Theses, 2020-current

Fucoxanthin is a carotenoid sourced and extracted mainly from dark orange and brown seaweeds found in the pacific ocean, such as the wakame algae. The allenic bonds and unique oxygen groups give fucoxanthin its unique structure and are thought to be part of the reason fucoxanthin has unique physiological functions. Fucoxanthin has potentially numerous effects on the physiology of human health, ranging from skin health to metabolic health, which have been demonstrated in animal model research. The goal of this review is to examine current literature to discuss fucoxanthin’s potential application as a nutraceutical, treatment for obesity, type 2 diabetes, …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

MSU Graduate Theses

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …