UMD Theses and Dissertations
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Item Regulation of Mitochondrial Metabolism and Lipogenesis(2021) Surugihalli, Chaitra; Sunny, Nishanth E; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Non-alcoholic fatty liver disease is one of the most common liver disorders with a global prevalence of over 25%. Fatty liver is the most common comorbidity of insulin resistance, obesity, and type 2 diabetes mellitus. During fatty liver, nutrient overload and the associated hyperinsulinemia results in elevated circulating free fatty acids and lipid accumulation in the liver. High rates of lipid accumulation in the liver is partly attributed to high rates of lipogenesis from carbohydrates, together with dysfunctional lipid oxidation. Further, these dysfunctional metabolic networks will induce oxidative stress and inflammation. Thus, understanding the metabolic mechanisms contributing towards the etiology of fatty liver and its associated morbidities is of major interest towards developing prevention and management strategies. This dissertation utilizes a combination of in-vivo (chicken and mice) and in-vitro (isolated mitochondria) systems with stable isotope-based methodologies to study metabolic regulation.Chicken embryos utilize yolk lipids (>45%), deriving over 90% of their energy through lipid oxidation for development. However, during the last few days of incubation and immediately after hatch, there is a substantial induction of lipogenesis. Despite the hepatic lipid overload, the synergistic remodeling of hepatic metabolic networks during embryonic-to-neonatal development blunted inflammatory onset, prevented accumulation of lipotoxic intermediates, and reduced reactive oxygen species production. Elevated plasma branched-chain amino acids (BCAAs) are a characteristic of insulin resistance and are relevant in predicting T2DM. Defects in BCAA degradation networks are also evident in several tissues during insulin resistance and associated co-morbidities. Furthermore, alterations in BCAA metabolism are associated with changes in lipogenesis and mitochondrial oxidative networks. We utilize a combination of isolated mitochondrial systems and stable isotope tracers in diet-induced mouse models of fatty liver, to determine its impact on mitochondrial metabolism and lipogenesis. In summary, the dissertation highlights i) the importance of the natural but dynamic remodeling of hepatic mitochondrial metabolism and lipogenesis during the efficient embryonic-to-neonatal transition in chicken ii) the significance of BCAAs as important regulators of hepatic mitochondrial lipid metabolism. Thus, these studies provide a platform to modulate hepatic metabolic networks and utilize the embryonic-to-neonatal transition phase and dietary intervention of BCAAs as management strategies to alleviate metabolic dysfunctions.Item "That Chart Ain't For Us": An Examination of Black Women's Understandings of BMI, Health, and Physical Activity(2019) Thompson, Tori; Jette, Shannon; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Significantly, black women have the highest rates of being overweight or obese compared to other groups in the United States, with 60% being classified as obese per the BMI (CDC, 2017). However, there is currently a lack of scholarship which examines black women’s perceptions of the BMI, and how/if those perceptions influence their attitudes toward health and physical activity. In this project, I take a Foucauldian approach to analyze data collected from eight semi-structured interviews with black women who self- identify as obese and who are physically active. Findings suggest that black women find the BMI to be irrelevant to their health and well-being, and do not attribute their engagement in physical activity to their BMI. Instead, their reasons for partaking in physical activity are due to their individual experiences understandings of health and black female identity. These results have the potential to inform healthcare policies, physician practice, and public health interventions that target communities of color.Item O-GLCNACYLATION IS NOT INCREASED IN THE HYPOTHALAMUS OF RATS GIVEN 6 WEEK ACCESS TO SUCROSE SOLUTION DESPITE MARKERS OF METABOLIC DYSREGULATION(2018) Hudgins, Samantha Morgan; Castonguay, Thomas W; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The peptide hormone leptin acts globally to maintain various metabolic processes. Impaired response to leptin binding is referred to as leptin resistance and results in metabolic dysregulation. Leptin is essential in the prevention of weight gain through central signals to increase energy expenditure and reduce food intake. A sugar sensitive pathway, the hexosamine biosynthesis pathway (HBP), may be the cause of diet induced leptin resistance. The HBP glycosylates proteins by modifying fructose- 6-phosphate molecules from glycolysis. While high sugar diets have been linked to leptin resistance, O-GlcNAcylation of pathway proteins have not been examined. Approximately 8-week-old male rats were assigned to ad libitum access to diet and water or 30% sucrose solution, diet and water. On Day 5 rats were surgically fitted with a third ventricle cannula. On Day 41, diet and sugar solutions were removed for an overnight fast. On Day 42 each rat received a central injection of leptin or control solution and subsequently euthanized 30 minutes post injection. Body weight and body composition were not significantly different between treatment groups after 42 days. However, the Sucrose group exhibited signs of metabolic syndrome, evidenced by increased fasting serum triglycerides and glucose as well as decreased serum HDL. Analysis of hypothalamic O-GlcNAcylation revealed no significant difference between treatment groups. These data may be the result of variability of glucose utilization within the hypothalamus. These data support previous findings that 42-day access to a 30% sucrose solution yields evidence of metabolic syndrome in the absence of obesity as well as the absence of increased hypothalamic OGlcNAcylation. Future research should examine O-GlcNAcylation regionally within the hypothalamus. Analysis of protein specific O-GlcNAcylation was not achieved; however, a novel O-GlcNAcylation was observed in hypothalamic tissue at the Threonine 1808 residue of prolow-density lipoprotein receptor-related protein 1 isoform X1 (LRP-1), a protein that may play a crucial role in leptin signaling. These data give further evidence to support the use of 30% sucrose solution to model leptin resistance in Sprague Dawley rats, as well as provide a target protein for future analysis.Item NECK CIRCUMFERENCE AS A NEW ANTHROPOMETRIC INDICATOR FOR PREDICTION OF CARDIOMETABOLIC RISKS IN SAUDI POPULATION(2016) Albassam, Reem Sulaiman; Lei, David; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Background: Recent studies have associated neck circumference (NC) with metabolic and cardiovascular disease risk factors. No studies designed to examine NC as a measure of cardiometabolic risks have been performed in Saudi Arabia (KSA). Objective: This study aimed to analyze the association between NC and several cardiometabolic risk factors, and to determine the cut-off point value of NC for predicting women at increased risk of metabolic syndrome (MetS). Methods: This cross-sectional study comprised of 700 participants (623 women and 77 men aged 18–70). Study performed in Riyadh city, KSA. International Diabetes Federation (IDF) guidelines were used to diagnose MetS among the subjects. The main indicators studied were NC, waist circumference (WC), body mass index (BMI), body fat %, blood pressure, plasma glucose, total cholesterol, lipoproteins, triglycerides, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels. Covariance, and logistic regression analyses were used to evaluate the association of NC to cardiometabolic risk factors separately by genders. Receivers operating characteristic (ROC) curves analyses were used to determine the optimal cutoffs. Results: NC is associated with BMI and WC in men and women. In women, it is associated with cardiometabolic risk factors beyond other anthropometric indices. NC is independently associated with all cardiometabolic risk factors except LDL (P < 0.001). Fully adjusted OR (95% CI) values for incremental increases in NC for women were 1.70 (1.48–2.94) for raised fasting glucose; 1.29 (1.15–1.45) for raised blood pressure; 1.25 (1.13–1.38) for high triglycerides; 1.20 (1.02–1.40) for insulin resistance; and 1.14 (1.02–1.40) for low HDLc. Women in the largest NC quartile were 13 times more likely [OR (95% CI): 13.39 (6.35 - 28.23)] to have MetS compared to the lowest NC quartile after adjustments for possible confounders (all P < 0.01). Finally, our results indicated that the appropriate NC to predict three or more metabolic risk factors in Saudi women is 35.5 cm. This cutoff value was associated with a much greater risk of MetS in participants with both high and normal BMI and WC values. Conclusion: NC is significantly and independently associated with cardiometabolic risk factors in adult Saudi women.Item The relationship of early social, mental, and behavioral experiences with adult obesity and Alcohol Use Disorder(2016) O'Neill, Allison Hunt; Lee, Sunmin; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Stressful life events early in life, including symptoms of mental disorders or childhood maltreatment, may increase risk for worse mental and physical health outcomes in adulthood. The purpose of this dissertation was to examine the effects of childhood Attention Deficit Hyperactivity Disorder (ADHD) symptoms and maltreatment experience on two adult outcomes: obesity and alcohol use disorder (AUD). Mediational effects of adolescent characteristics were explored. This dissertation used Waves I, III, and IV of the National Longitudinal Study of Adolescent to Adult Health. In Paper 1 (Chapter 3), we investigated the association between multiple types of child maltreatment and adult objective (body mass index; BMI) and subjective (self-rated) obesity, as well as mediating effects by adolescent characteristics including depressive symptoms and BMI. Results showed that after adjusting for sex, race/ethnicity, and maternal education, physical maltreatment was moderately associated with adulthood obesity as measured by BMI and self-reported obesity, while sexual maltreatment was more strongly associated with the objective measure but not the subjective measure. The indirect effects of mediation of adolescent BMI and depressive symptoms were statistically significant. In Paper 2 (Chapter 4), the objective was to examine mediation by adolescent depressive symptoms, alcohol consumption, peer alcohol consumption, and delinquency in the relationship between ADHD symptoms and adult AUD. The indirect effects of mediation of adolescent delinquency, alcohol consumption, and peer alcohol consumption were statistically significant in single and multiple mediator models. In Paper 3 (Chapter 5), the objective was to assess the joint effects of maltreatment/neglect on adult AUD. After adjusting for sex, race/ethnicity, child maltreatment, and parental AUD, ADHD symptoms were significantly associated with increased odds of AUD. There was no strong evidence of multiplicative interaction by maltreatment. This association was stronger for males than females, although the interaction term was not statistically significant. This dissertation adds to the literature by examining relationships between several major public health problems: ADHD symptoms, childhood maltreatment, AUD, depressive symptoms, and obesity. This project has implications for understanding how early life stress increases risk for later physical and mental health problems, and identifying potential intervention targets for adolescents.Item Too Much to Belong: Latina/o Racialization, Obesity Epidemic Discourse, and Unassimilable Corporeal Excess(2016) Griff, Ellen Cassandra; Paoletti, Jo B; American Studies; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This project examines the discursive constructions of Latina/o bodies as excessive in order to examine how Latinas/os are excluded from belonging to the U.S. nation-state. By approaching Latina/o Studies from a Fat Studies perspective, it works to more adequately address the role of embodiment in determining processes of racialization that directly impact Latinas/os in the United States, especially in light of the role of race and racism in “obesity epidemic” discourse. This dissertation argues that cultural and even physiological explanations about the Latina/o propensity for “overweight” and “obesity” create a discourse that marks the Latina/o body as demonstrating an unassimilable corporeal excess. In turn, the rhetoric of “diversity” and “multiculturalism” are rendered inapplicable to Latinas/os, as demonstrated by both nativist and seemingly pro-immigrant discourses that posit Latina/o physical excess in the form of fatness as detrimental and even dangerous to the U.S. nation-state.Item THE EFFECTS OF SUGAR INTAKE ON ENERGY CONTROL(2015) Zhao, Changhui; Castonguay, Thomas W; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Long term use of sugars can induce excess caloric intake and/or obesity. To evaluate the effects of sugar intake on different regions of the hypothalamus (the brain's control center for energy homeostasis) we first developed and then evaluated a microscope-assisted dissection method. Because of the small size of the paraventricular nucleus, we validated the samples by measuring several hormones mainly synthesized in the paraventricular nucleus. These include corticotropin-releasing hormone, oxytocin, arginine vasopressin and thyrotropin releasing hormone. We measured the mRNA expression of each of these hormones using quantitative PCR and detected them principally in the paraventricular nucleus. We further evaluated the effects of various sugar solutions on the expression of several important hypothalamic neuropeptides because they play a pivotal role in energy homeostasis. We provided Sprague Dawley rats 24 hour access to 15% solutions of glucose, fructose, sucrose or high fructose corn syrup. We then measured the expression of several neuropeptides in different hypothalamic regions, all of which were previously shown to be influenced by sugar consumption (mainly based on the results from a series of PCR arrays). Additionally, we measured plasma leptin, known for its close correlation with body fat mass. As expected, rats that had access to sugar solutions consumed less chow. However, rats with free access to sugar solutions maintained a similar amount of energy intake compared with control. Of the four sugars tested, only fructose decreased expression of cholecystokinin significantly, whereas glucose and sucrose significantly increased the expression of tumor necrosis α only in the paraventricular nucleus, not in the ventromedial nucleus or the lateral hypothalamic area. Fructose and sucrose decreased growth hormone expression in the ventromedial nucleus. Glucose increased dopamine receptor D1A expression in the paraventricular nucleus only. We conclude that 24 hour free access to different sugars can influence the expression of several hypothalamic neuropeptides in different ways and these changes are region dependent. Changes in the expression of these neuropeptides do not disrupt the total energy intake immediately but may contribute to the obesity caused by long term intake of sugars.Item Sleep Duration in Adolescent Girls: Correlates and Association with Obesity Risk(2013) Moshkovich, Olga; Saksvig, Brit I; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The present study aimed to identify demographic, behavioral, and school-related factors associated with week night sleep duration among an ethnically diverse sample of 582 adolescent girls from the Trial of Activity for Adolescent Girls (TAAG) 2. The distribution of sleep duration categories (<7 hours, 7-9 hours, and >9 hours) differed significantly among ethnic groups in bivariate analyses, but not in the final multivariate model. Additionally, sleep duration was negatively associated with distance to school from home, typical time spent on the computer, and school start time. In contrast to previous findings, shortened sleep duration was not associated with increased body mass index (BMI), body fat percentage, or quantity of moderate-to-vigorous physical activity (MVPA). Findings show support for delayed school start times. In addition, future research should examine whether interventions to reduce screen time activities among adolescents is effective in increasing their sleep duration.Item B Cell Memory, CD23, and Lipid Metabolism: A Preliminary Study(2012) Wiggins, Melvin Daniel; Song, Wenxia; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)We each receive vaccinations throughout our lives, which protect us from many pathogens and gives long-term protection through generating a subset of memory lymphocytes. This study explores whether CD23 (Fcε receptor) and high fat diet have roles in regulating memory B cells. CD23 in B cells was examined using CD23 transgenic mice. My data show that, after antigenic stimulation, CD23 co-aggregates with the BCR. The percentages of isotype switched B cells as well as other peripheral B cell subsets in the spleen are not altered in unimmunized CD23 transgenic mice, implicating that CD23 does not have any significant role in the generation of memory B cells. High fat diet with and without high cholesterol led to increased numbers of mature follicular B cells and decreases in transitional B cells in a NPC1L1 independent manner.The marginal zone B cells numbers are increased in the mice fed high fat/high cholesterol diets. This suggests a possible role of high fat/high cholesterol diet in regulating the peripheral development of B cells.Item Observations regarding consumption of Peruvian native grains (quinoa, amaranth and kañiwa), weight status, and perceptions of potential risk factors, warning signs and symptoms of type 2 diabetes among Peruvian adults: A case study(2012) Sanchez, Katherine A.; Kantor, Mark A; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Wheat flour-based foods and rice have replaced native cereals in the diets of many urban-living Peruvians. Urban areas have also seen increases in overweight, obesity, and type 2 diabetes mellitus prevalence in recent years. The focus of this research is to describe observations regarding consumption of quinoa, amaranth and kañiwa cereals; weight status; and self-described experiences of potential risk factors and warning signs for, and symptoms that may represent complications of, type 2 diabetes mellitus in Peruvian adults living in the city of Arequipa. A survey instrument was developed and administered to 110 subjects (22 diabetics, 88 non-diabetics), middle-aged and over. Participants with normal BMIs consumed quinoa, amaranth, and kaniwa more frequently than overweight or obese participants. Diabetics reported more frequent consumption of Andean cereals, particularly amaranth, and less frequent consumption of white flour than non-diabetics. Most participants reported eating a diet high in carbohydrates and leading a sedentary lifestyle.