Life Sciences Commons^™

Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda

Arts & Sciences Electronic Theses and Dissertations

Pancreatic β-cells perform glucose-stimulated insulin secretion, a process required to maintain systemic glucose homeostasis. Obesity promotes glycemic and inflammatory stress, causing β-cell death and dysfunction, resulting in diabetes. Efforts to improve β-cell function in obesity have been hampered by observations that β-cells are highly heterogeneous, varying in morphology, function, and gene expression. There is great need to understand the breadth of β-cell heterogeneity in health and obesity to improve diabetic therapies.High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we show that as they resolve hyperglycemia, obese SM/J …

The Good, The Brown, And The Healthy: Understanding Non-Thermogenic Brown Adipose Function In Obese Mice, Caryn Nicole Carson

Arts & Sciences Electronic Theses and Dissertations

Genetic and environmental factors heavily intertwine to affect metabolic homeostasis. To tease out the exact interactions between these two realms of influence, researchers often compare how one or multiple different inbred mouse strains react to various diets. An observation consistently seen across multiple strains on the same diet can reasonably be considered a general dietary effect, whereas an observation seen only in one strain of mice is more likely to result from a genetic cause or gene-by-environment interaction. Similarly to humans, a high fat diet causes many mouse strains to develop obesity and poor metabolic health, with varying degrees of …

Pillars Of The Nutrition Transition: The Global Impacts Of Ultra-Processed Foods And Beverages On Overweight And Obesity And National Nutrient Supplies, Jacob Eaton

Arts & Sciences Electronic Theses and Dissertations

Malnutrition in some form impacts nearly one-third of the global population. Across the world, countries are undergoing the Үutrition transitionӠfrom traditional and largely unprocessed diets to Western-style, energy-dense diets. At the same time, rates of overweight and obesity and diet-related chronic diseases continue to climb. Ultra-processed foods (UPF), sugar-sweetened beverages (SSB), and vegetable oils are three of the foods driving the nutrition transition. This dissertation calculates changes in the global food supply between 1961 and 2013 and quantifies the influence of UPF and SSB (as measured through sales) on national nutrient supplies between 2005 and 2013 and trends in adult …

Dismantling Of Obesity-Related Policies, Alexandra Borosova Morshed

Arts & Sciences Electronic Theses and Dissertations

This dissertation fills an important research gap in the study of obesity policymaking by characterizing to what extent the phenomenon of dismantling is happening at the state level for obesity-related policies targeting the context of consumption, identifying determinants, and characterizing actors and processes involved. The five-year rate of dismantling of these policies is close to one-third for any attempts and one-tenth for enacted dismantling. Food and beverage tax policies face a particularly high rate of dismantling. Case studies and news coverage of state- level dismantling identified actors, motivations, and strategies used in the process of dismantling. Review of health-related empirical …

The Effect Of Dietary Fat On Obesity, Gene Expression, And Dna Methylation In Two Generations Of Mice, Madeline Rose Keleher

Arts & Sciences Electronic Theses and Dissertations

As obesity rates continue rising nationally and globally, it is crucial to understand how a high-fat diet disrupts the regulation of the genome and leads to adverse health effects. Uncovering the underlying gene expression and DNA methylation changes induced by an individual’s high-fat diet and a maternal high-fat diet can pinpoint new targets for epigenetic therapies and reveal the physiological and behavioral changes in obesity. The goal of this dissertation is to gain deeper insight into the DNA methylation and gene expression changes that occur in response to a high-fat diet.

I studied the response to dietary fat within two …

Mitochondrial Damage Accumulation In Oocytes – A Potential Link Between Maternal Obesity And Increased Cardiometabolic Disease Risk In Offspring., Anna Louise Boudoures

Arts & Sciences Electronic Theses and Dissertations

The developmental origins of health and disease (DoHAD) hypothesis suggests that negative maternal lifestyle choices, such as obesity, affect the health of her offspring. Clinical and laboratory studies support this hypothesis – offspring born to obese mothers are at increased risk for health conditions including cardiometabolic syndrome and congenital abnormalities. Maternal obesity damages the oocytes, contributing to the increased disease risk by transmitting damaged organelles and epigenetic modifications to the offspring. Mitochondria, the most abundant organelle in the oocyte, are damaged in oocytes from obese females. However, we do not understand if mitochondrial damage in oocytes is reversible nor why …

Physical Activity And Maternal And Neonatal Outcomes In Obese Pregnant Women, Rachel Ann Tinius

Arts & Sciences Electronic Theses and Dissertations

Maternal obesity and physical inactivity during pregnancy are independently associated with unfavorable maternal and neonatal metabolic outcomes. Previous research in non-gravid adults suggests physical activity provides protection from many chronic diseases irrespective of body weight. The primary purposes of this dissertation were to determine the impact of obesity on maternal metabolic health (lipid metabolism, inflammation, insulin resistance) and neonatal metabolic health (adiposity, inflammation, insulin resistance), and to determine if adverse maternal and neonatal metabolic health is improved in obese pregnant women who are physically active during pregnancy compared to sedentary obese women. The secondary purpose of this dissertation was to …

Ketone Body Metabolism Preserves Hepatic Function During Adaptation To Birth And In Overnutrition, David Graham Cotter

Arts & Sciences Electronic Theses and Dissertations

Mammalian ketone body metabolism partially oxidizes hepatic acyl-chains to ketone body intermediates, which can serve as alternative fuels in extrahapetic tissues during carbohydrate restricted states. Ketone body production (ketogenesis) occurs primarily in liver, due to hepatocyte-specific expression of the fate committing ketogenic enzyme, mitochondrial 3-hydroxymethylglutaryl-CoA synthase (HMGCS2). In contrast, the fate committing enzyme of ketone body oxidation, mitochondrial Succinyl-CoA:3-oxoacid CoA Transferase (SCOT), is expressed ubiquitously, except in liver. Here I demonstrate novel roles for ketone body metabolism during a classically ketogenic period, the transition to birth, and in a classically `non-ketogenic' state, overnutrition, using novel genetic mouse models, high-resolution measures …

A Ranksum Statistics Based Framework To Decipher Transcription Regulation, Iuan-Bor Chen

Arts & Sciences Electronic Theses and Dissertations

The unbiased generation of specific and meaningful hypotheses from the deluge of data generated by modern genomic methods remains a challenge. These datasets require increasing level of expertise to analyze fully, and are often underutilized even in the originating lab. It would be desirable to have a computational strategy that is easy to implement, robust against outliers and missing data, and broadly applicable to diverse experimental designs. In this dissertation, I present a set of ranksum statistics-based analytical methods as a framework to extract testable hypotheses from large and complex datasets. To illustrate its utility, this framework was applied to …