Medicine and Health Sciences Commons^™

Attenuation Of Interferon Responses In The Obese Host And Ramifications For Influenza Virus Evolution, Rebekah Reed Honce

Theses and Dissertations (ETD)

The most insidious pandemic of modern life does not arise from an infectious agent but rather from malnutrition. With its global incidence tripling over the past three decades, obesity is a major public health concern. Obesity’s rising prevalence has also illuminated its impact on communicable diseases. Following the 2009 H1N1 influenza A virus pandemic, obesity was identified as a risk factor for increased disease severity and mortality in infected individuals. Obesity causes a chronic state of meta-inflammation with systemic implications for immunity, including delayed antiviral responses to influenza virus infection, poor recovery, and impaired immunological memory. However, the majority of …

Investigating Pathways Associated With Intervertebral Disc Degeneration And Back Pain., Geoffrey J. Kerr

Electronic Thesis and Dissertation Repository

Lower back pain (LBP) is one of the most common conditions worldwide, yet, current therapeutics are limited to symptomatic relief and do not directly treat the underlying cause of pain. This is largely due to an incomplete understanding of the biological pathways and tissues involved in LBP. While many tissues appear to be involved, intervertebral disc (IVD) degeneration is believed to be a major contributor.

The main aim of this thesis was to characterize the role of two environmental risk factors, mechanical loading and obesity, in the initiation of IVD degeneration and associated pain using the mouse as a preclinical …

Association Of Body Mass Index Genetic Risk Markers With Body Composition During Adolescence, Brice A. Smoker

Senior Theses

Background. Obesity affects nearly a fifth of all children in the United States and is a common risk factor for numerous chronic diseases. Many risk factors contribute to obesity, including race and genetics. Obesity is partially heritable, and many genetic loci have been identified as being associated with body mass index (BMI) in adults. Some of these loci have also been associated with childhood BMI, with effects strengthening with age. A previous genome-wide association study (GWAS) identified five single nucleotide polymorphisms (SNPs) associated with changes in BMI in children aged 1 – 17 years.

Purpose. The purpose of the current …

Downstream Pathways Of Glucagon Receptor Agonism In Obesity, Shelly Nason

All ETDs from UAB

Obesity is highly prevalent and strategies to improve weight loss maintenance are critical for healthcare. Behavioral interventions are effective but require major lifestyle changes that are often difficult to maintain long-term. Therefore, modifying energy balance with pharmacotherapy is a strategy to combine with lifestyle modifications for sustained weight loss. Glucagon, a hormone involved in maintaining glucose homeostasis, also regulates energy expenditure, food intake, and lipid metabolism. As such, glucagon-based therapies have gained attention as an attractive clinical target. Glucagon Receptor (GCGR) mono-agonism induces glucose intolerance; therefore, dissecting the mechanisms by which GCGR signaling mediates energy balance are clinically relevant to …

Understanding The Impact Of Diet And Obesity On Anti-Tumor Immunity And Therapeutic Efficacy In Kidney Cancer, Rachael Miller Orlandella

All ETDs from UAB

Obesity is regarded as a major risk factor for developing renal cell carcinoma (RCC). Advanced-stage RCC exhibits chemotherapeutic resistance, but is responsive to immunotherapies such as the immune checkpoint inhibitor anti-programmed cell death-1 (anti-PD-1). Despite some clinical successes, response rates remain low for anti-PD-1 monotherapy (20-30%). Preclinical evaluations of immunotherapeutic strategies typically use lean mice and do not account for patient comorbidities. This may explain the underwhelming success rates following clinical translation of new cancer treatments. Recent studies found that obesity was associated with favorable outcomes and responses to immunotherapy in melanoma. However, the effects of obesity on anti-tumor immunity …

Circadian Clock And Lipid Metabolism Disruption In Fatty Liver Disease, Jennifer Valcin

All ETDs from UAB

Hepatic Steatosis, characterized by the accumulation of triglyceride (TG) in the liver is the first stage of Alcoholic Liver Disease (ALD) and Nonalcoholic Fatty Liver Disease (NAFLD). Many metabolic pathways, including lipid metabolism, are regulated by the molecular circadian clock. Importantly, alcohol consumption and obesity induce circadian clock disruption, a risk factor for many diseases, including liver disease. In our first study, we investigated the combined effect of clock disruption and alcohol feeding on liver pathology, and diurnal rhythms in the liver molecular clock and lipid metabolism. Male liver-specific Bmal1 knockout (LKO) mice and control littermates were fed a control …

Obese Zucker Rats As A Reverse Translational Model Of Human Left Ventricular Hypertrophy, Mackenzie Shelby Newman

Graduate Theses, Dissertations, and Problem Reports

Heart failure is a lifelong disability that for over half of those affected leads to mortality within five years after initial diagnosis. Left ventricular hypertrophy (LVH) is one of the most reliable independent predictors of heart failure. Pathological LVH is irreversible, but early diagnosis is often missed due to its asymptomatic nature. Obese Zucker rats (OZR), which develop obesity due to dysfunctional leptin signaling, naturally exhibit a LVH that mimics the obese human condition. Animal models are necessary because human donor tissue is scarce. The central hypothesis is that genes and proteins that are differentially expressed during development of LVH, …