Molecular, Genetic, and Biochemical Nutrition Commons^™

Alzheimer’S Disease Genetics And Short-Chain Fatty Acid Treatment In Studies Of The Murine Gut Microbiome, Diana Zajac

Theses and Dissertations--Physiology

Elucidating the relationship of the gut microbiome in Alzheimer's Disease (AD) risk and pathogenesis is an area of intense interest. Since 60 to 80% of AD risk is related to genetics and APOE alleles represent the most impactful genetic risk factors for AD, their mechanism(s) of action are under intense scrutiny.

First, I conducted a study on APOE targeted replacement mice to investigate the impact of APOE alleles on the murine gut microbiome. The relative abundance of bacteria from the family Ruminococacceae and related genera increased with APOE2 status. The relative abundance of the class Erysipelotrichia increased with APOE4 status, …

Appetite-Regulating Hormones In Energy Compensation With Exercise, Jack Moreland

Theses and Dissertations--Nutrition and Food Systems

Background: The appetite-regulating hormones may influence compensatory increases in energy intake with exercise, although this causal relationship has been difficult to prove in a longitudinal trial.

Methods: 37 participants (29 female) aged 18 to 40 years performed aerobic exercise 6 days (6d), 2 days (2d), or 0 days per week for 12-weeks. Concentrations of ghrelin, leptin, glucagon-like peptide 1 (GLP-1), and insulin were assessed before (fasting, minute 0) and after a standardized meal at minute 15, 30, 45, 60, 90, 120, 150, and 180. Linear mixed-effects models were used to model the relationships between time point (12 weeks vs. baseline) …

Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer

Theses and Dissertations--Physiology

Altered metabolic pathways appear to play central roles in the pathophysiology of late-onset Alzheimer’s disease (AD). Carrier status of the E4 allele of the APOE gene is the strongest genetic risk factor for late-onset AD, and increasing evidence suggests that E4 carriers may be at an increased risk for neurodegeneration based on inherent metabolic impairments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role. In chapter 1, the literature on nutritional interventions in E4 carriers aimed at mitigating disease risk is reviewed. Studies investigating the mechanism by which …

Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death among critically ill patients that results in metabolic alterations including hypercatabolism, lipoatrophy, and muscle wasting, contributing to the development of cachexia. Septic cachexia is associated with loss of body weight, fat mass, and lean mass and dysregulated immune function. There are currently no efficacious treatment strategies for septic cachexia, and nutritional interventions have limited success in preventing hypercatabolic wasting. Pyocyanin is a virulence factor produced by sepsis-causing Pseudomonas aeruginosa that has been shown to activate the aryl hydrocarbon receptor (AhR), increase inflammation, and produce reactive oxygen species. Thus, pyocyanin represents a novel mechanistic …

The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …

The Role Of Exercise In Polychlorinated Biphenyl Induced Cardiovascular Disease, Margaret O'Bryan Murphy

Theses and Dissertations--Nutritional Sciences

Cardiovascular disease remains the leading cause of death in Western societies. Endothelial dysfunction is one of the initiating steps in the development of atherosclerosis. While there is a strong correlation with a person’s genetics, lifestyle factors including smoking, physical activity, and diet can significantly increase a person’s susceptibility to the development of atherosclerosis. In addition to these lifestyle factors, there is a strong body of evidence linking exposure to environmental pollutants including persistent organic pollutants such as polychlorinated biphenyls to increased cardiovascular disease and mortality. It has been well-established that exercise protects against cardiovascular disease, but whether exercise can modulate …