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Retinoic Acid, Insulin, And Cycloheximide Alter Glycogen Homeostasis In Differentiating L6 Myoblasts, Aaron Armstrong

Doctoral Dissertations

Glycogen synthesis in skeletal muscle (SM) is responsible for the majority of post-prandial glucose disposal in healthy individuals. In type 2 diabetes mellitus (T2DM), compromised skeletal muscle glycogen synthesis contributes to hyperglycemia. L6 rat SM cells can develop insulin resistance with prolonged insulin stimulation and provide an in vitro model for mechanistic dysfunction in glycogen homeostasis. SM glycogen is synthesized by glycogen synthase (GS) in response to insulin stimulation. Canonically, insulin signaling increases GS activity through inhibition of its Ser641 regulator glycogen synthase kinase-3β (GSK3β) by protein kinase B (AKT). Proximal insulin signaling activates AKT via Ser473 phosphorylation which proceeds …

Metabolism In The Colonocyte: Where Bacteria And Diet Meet, Bohye Park

Doctoral Dissertations

The host-microbiome interaction and the functions of microbial-derived metabolites, including butyrate, are important in colon health. Butyrate is the preferred energy source in colonocytes and has multiple physiological functions in the colon. A metabolic shift in colonocytes toward increased glucose utilization from butyrate oxidation is followed by several critical genetic modifications in cancerous colonocytes. Moreover, it has been suggested that the gut-microbiota composition is influenced by environmental factors, such as diets and the host's physiological status. Therefore, an understanding of the role of colonocyte metabolism toward impacting the host-microbiota commensal relationship would be an important step in understanding the functional …

The Studies Of Effects Of Vitamin A Status On Type 2 Diabetes In Zucker Diabetic Fatty Rats And Retinoic Acid On Glucose Transporter 4 Expression In L6 Cells, Tiannan Wang

Doctoral Dissertations

The epidemic of metabolic diseases such as diabetes has become a public health concern. Previous research data from our lab have shown that vitamin A (VA) status and retinoic acid (RA), a metabolite of VA, contribute to the glucose and lipid metabolism in the body and cells. As the skeletal muscle contributes to metabolic homeostasis, the effects of VA signaling system on its glucose metabolism are worth to be investigated. Here in this dissertation, the following two projects were carried out to study the VA’s role in the control of metabolism. (1) The effects of VA status on the development …

Effects Of N-3 Pufa-Derived Epoxides Combined With Seh Inhibition On Brown Adipose Tissue And Brown Adipocytes In Obesity, Yang Yang

Doctoral Dissertations

Brown adipose tissue (BAT) has become a promising target for obesity treatment and prevention. However, effective dietary factors to promote BAT mass and function have not been identified. 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are two prominent epoxy fatty acids (EpFAs) produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. EpFAs are quickly metabolized to less active diols by soluble epoxide hydrolase (sEH). In this dissertation, the effects of an sEH inhibitor (t-TUCB) (which stabilizes EpFAs) alone or combined with n-3 EpFAs on thermogenic activity in the BAT and brown adipocytes in …

Using A Cognitive Behavioral Approach In Individual Counseling With Patients Undergoing Bariatric Surgery, Nina Marie Ditommaso

Doctoral Dissertations

Morbid obesity is linked to physical and psychological well-being. Bariatric surgery has shown tremendous success with rapid weight loss in the patient population with morbid obesity. These patients experience issues with weight regain post-surgery, which can be linked to psychological and social factors. Despite this, mental health counseling is rarely offered in bariatric surgery programs. The primary investigator used a six-session Cognitive Behavioral Therapy (CBT) approach in individual counseling with patients following bariatric surgery. The primary investigator used a single case research design to treat four participants. The primary investigator measured the effectiveness of a six-session CBT treatment, assessing for …

Novel Insights Into The Role Of Pyruvate Kinase M2 In Podocyte Homeostasis And Function, Mohammed Alquraishi

Doctoral Dissertations

Background: Renal diseases are major health concerns and among the top ten leading causes of death in the US. A large number of these diseases are characterized by deterioration in glomerular structure and function, leading to reduced filtration capacity and proteinuria. Glomerulus podocytes are epithelial cells that maintain glomerular integrity and act as a defense mechanism against proteinuria. Recent advances in renal research suggested a novel role of glycolysis and its related enzymes, pyruvate kinase M2 (PKM2) in particular, in the progression of renal diseases. However, the precise role of PKM2 in podocyte homeostasis and its contribution to glomerular function …

Butyrate, A Major Bacterial-Derived Metabolite: Understanding Of Butyrate Metabolism In Cancerous Colonocytes, Anna Han

Doctoral Dissertations

The prohibitory effects of dietary fiber in colorectal cancer have been identified, although the detailed mechanism of this beneficial effect remain unclear. Butyrate, a fermentation metabolite of fiber, has anti-cancer properties by inhibiting cell proliferation and increasing cell apoptosis in cancer cells. A major mechanism, whereby butyrate exerts anti-cancer effects in colorectal cancer, is its role as an HDAC inhibitor. Moreover, it has been suggested that the metabolic fate of butyrate is significantly related to its role as an HDAC inhibitor. Therefore, understanding butyrate metabolism in cancerous colonocytes sheds important light on how butyrate has its selective and inhibitory effects …

Development, Implementation And Evaluation Of A Pilot Intervention: Promoting Breast Milk Expression In A Neonatal Intensive Care Unit, Katherine Marie Bower

Doctoral Dissertations

Background: Very preterm infants receiving breast milk experience better health outcomes compared to formula fed infants. However, these infants often lack the ability to coordinate sucking and swallowing and are unable to breastfeed at delivery. Consequently, mothers of very preterm infants must initiate milk expression. While these mothers demonstrate high milk expression initiation rates, continuation of this behavior until infant discharge from the Neonatal Intensive Care Unit (NICU) is a significant challenge.Therefore, the primary aim of this study was to gain an understanding of mothers’ experiences expressing milk for their very preterm infants in a Level III NICU and to …

Long-Term Treatment With Insulin And Retinoic Acid Increased Glucose Usage In L6 Muscle Cells Via Glycogenesis, Matthew Ray Goff

Doctoral Dissertations

Skeletal muscle glucose metabolism can affect whole body glucose homeostasis significantly. Vitamin A (VA) plays a role in a number of physiological functions including glucose metabolism. However, its role in skeletal muscle glucose metabolism has not been well established. Insulin controls glucose metabolism in the skeletal muscle via the regulations of glucose uptake, glycogenesis, and glycolysis. We hypothesize that insulin and VA signaling pathways may converge to regulate glucose metabolism in skeletal muscle. Here, the effects of retinoic acid (RA) alone and in combination with insulin on glucose utilization in rat L6 muscle cells were studied. L6 cells were treated …

Brown And Beige Adipocytes: Effects Of Inflammation And Nutritional Intervention, Jiyoung Bae

Doctoral Dissertations

Recent findings of brown adipocytes and brown-like or beige adipocytes, capable of dissipating energy as heat, in adult humans have promised new hope for obesity treatment and prevention. Understanding of the regulation of brown and beige adipocytes will provide novel strategies to reach the goal. Pattern recognition receptors (PRR) are responsible for inflammation in adipose tissue, which leads to adipose dysfunction and obesity associated chronic diseases. It has been shown that PRR activation induces inflammation, leading to insulin resistance in white adipocytes and white adipose tissue (WAT). However, the roles of PRR activation in brown adipocytes and brown adipose tissue …

The Use Of Videoconferencing For Lactation Consultation: A Cross-Sectional Survey Of Acceptance Among Independent Samples Of Mothers And Infant Fathers/Maternal Partners In The United States, Mona F. Habibi

Doctoral Dissertations

Background: Breastfeeding is a health behavior encouraged by Healthy People 2020. However, an important barrier to breastfeeding is limited access to specialized support if needed. The use of videoconferencing technology to increase access to the relatively small number of professionals trained to manage breastfeeding issues may ultimately assist with increasing breastfeeding duration and exclusivity rates. Understanding the perceived acceptability of videoconferencing technology among potential users is a critical first step in developing effective interventions.

Objectives: The objectives of this study were 1) to assess the relationship between acceptance of remote lactation consultation using videoconferencing and a) acceptance subscales, b) maternal …

Exploring Novel Environmental Link To Obesity: Role Of Parabens In Adipogenesis In Vitro And In Vivo, Pan Hu

Doctoral Dissertations

Parabens are a group of alkyl esters of p-hydroxybenzoic acid that include methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben. Paraben esters and their salts are widely used as preservatives in cosmetics, toiletries, food, and pharmaceuticals. Humans are exposed to parabens through the use of such products from dermal contact, ingestion, and inhalation. The extent of the exposure is reflected by the frequent detection of these compounds in urine samples in the general population. Moreover, parabens have been detected in human serum, milk, placental tissues and breast tumor tissues. Parabens have been shown to preserve estrogenic/antiandrogenic effects, and can activate peroxisome proliferator-activated …

Calcium And Leucine Modulation Of Airway Inflammation, Patricia Louise Brown

Doctoral Dissertations

Over the past several decades the prevalence of obesity and asthma have increased in a parallel fashion. Recent studies reported a positive relationship between the two disorders that may in fact be causal. Although the link between obesity and asthma has become widely recognized, the underlying pathophysiological connection is not elucidated. Increased markers of inflammatory and oxidative stress are present in obesity and asthma suggesting the link is immunological. The systemic inflammation observed in obesity may potentially initiate adverse affects in the airways. Previous studies have shown that consumption of dairy foods (rich in calcium and leucine) suppress 1,25-dihydroxycholecalciferol (calcitriol) …

Role Of Vitamin A Status And Its Catabolism In The Regulation Of Glucose And Lipid Homeostasis In Rats Under Physiological And Disease Conditions, Yang Li

Doctoral Dissertations

The increased number of individuals with metabolic diseases has become a public health concern. Vitamin A (VA, retinol) is required to maintain the general health of an individual. How VA contributes to the regulation of glucose and lipid homeostasis in normal and metabolic disease states is unclear. VA’s physiological activities are mainly mediated by its metabolite, retinoic acid (RA), which activates several transcriptional factors in the nuclear receptor super family and in turn, regulates the expression of numerous genes for macronutrient metabolism. For the RA production, retinol is first oxidized into retinal and then from retinal to RA. We hypothesize …

Role Of Leucine In Modulation Of Mitochondrial Biogenesis And Sirt1-Ampk Signaling In C2c12 Myotubes, Chunzi Liang

Doctoral Dissertations

Mitochondrial dysfunction in skeletal muscle has been considered as a crucial step in the development of metabolic diseases, including insulin resistance syndrome, type 2 diabetes and cardiovascular diseases. Previous studies have demonstrated that dietary branched-chain amino acids, particularly leucine, protects against high-fat diet induced impairment of mitochondria and insulin resistance in skeletal muscle and adipose tissue through mTOR-dependent and independent pathways. In addition, previous ex vivo and in vitro approaches from this laboratory indicate that leucine and its metabolites (HMB and KIC) stimulate mitochondrial biogenesis and promote energy partitioning from adipocytes to muscle cells, partially through SIRT1 signaling. Moreover, recent …

Feeding State, Vitamin A Status And Atypical Protein Kinase C Modulate The Insulin-Regulated Gene Expression In Rat Hepatocytes, Wei Chen

Doctoral Dissertations

Hormonal and nutritional stimuli coordinately regulate the glucose and lipid metabolism in the liver. Dysregulated hormonal balance and nutrient metabolism not only disrupt the energy homeostasis, but also predispose individuals to the development of obesity and its related metabolic diseases. Research presented in this dissertation investigated the effects of a nutritional factor, vitamin A (VA), and a potential component of insulin signaling cascade, atypical protein kinase C (aPKC), on the glucose and lipid metabolic genes transcription in primary hepatocytes from Zucker lean (ZL) and fatty (ZF) rats.

To examine VA effects, we put ZL and ZF rats with different VA …

The Effects Of Leucine And Dairy Products On Adipose Tissue Inflammation: The Role Of Adipocyte Derived Microvesicles, Benjamin Jones Curry

Doctoral Dissertations

Obesity is characterized by chronic oxidative and inflammatory stress, and adipose tissue is a significant source of inflammatory cytokines. Previous studies demonstrated that dairy products (rich in calcium and leucine) can alleviate obesity-associated inflammatory stress through suppression of 1, 25-dihydroxycholecalciferol (calcitriol) with calcium and the high leucine content in dairy. We have also shown leucine treatment increases anti-inflammatory adiponectin expression and decreases pro-inflammatory cytokines TNF-a [alpha], MCP-1, and IL-6 expression in adipocytes. Therefore, we sought to determine if these alterations in inflammatory cytokine production could have a functional effect on the inflammatory process, specifically monocyte – endothelial cell adhesion as …

Exploration Of Breastfeeding Concepts Among Current And Future Parents: Results Of Questionnaires Administered To Chinese And Us University Students And To New Mothers In China, Zixin Lou

Doctoral Dissertations

The objectives were to explore breastfeeding knowledge, attitudes, and intention of future parents, and to investigate indicators and causes of perceived insufficient milk (PIM) supply among Chinese mothers. Objectives were accomplished using a cross-sectional study design. Two questionnaires were developed, one targeting Chinese and US undergraduates, and a second targeting Chinese mothers. In total, 597 undergraduates (395 Chinese; 202 US) and 392 Chinese mothers participated in the study. Data cleaning resulted in a final sample size of 572 for undergraduates (383 Chinese; 189 US) and 341 for Chinese mothers. Results showed that undergraduates in both countries possessed some breastfeeding knowledge …

Role Of Retinoids In The Regulation Of Hepatic Glucose And Lipid Metabolism, Rui Li

Doctoral Dissertations

The liver plays an important role in controlling glucose and lipid homeostasis. Metabolic abnormalities such as obesity and type 2 diabetes are often associated with profound changes in the expression of genes involved in hepatic glucose and lipid metabolism. Dietary nutrients provide us with macronutrients for energy and micronutrients for maintenance of general health. However, the effects of individual micronutrients on the development of metabolic diseases are unknown. Sterol regulatory element binding protein-1c (SREBP-1c) is the master regulator of fatty acid synthesis, and glucokinase (GK) is the key enzyme in glucose metabolism. Based on the preliminary results from our laboratory …

A Pilot Study Of The Efficacy And Program Cost-Effectiveness Of Prevention Plus For Childhood Obesity, Shannon Marie Looney

Doctoral Dissertations

Background: In 2007 an Expert Committee published recommendations using a staged approach for the treatment of childhood obesity in the primary care setting. Limited research has evaluated the efficacy of these recommendations. Thus, the primary aim of this study was to test the efficacy of Prevention Plus for the treatment of childhood overweight and obesity in a primary care setting. Cost is a major barrier to translation of research into practice thus, program cost-effectiveness was also evaluated. Methods: Twenty-two children (8.0 ± [plus-minus] 1.8 years; 2.34 ± 0.48 z-BMI; 68.2% female, 72.7% White, 90.9% non-Hispanic) were randomized to one of …

Effects Of Folate Availability On Expression Of Adipocyte Metabolic Genes Via Modulation Of Dna Methylation, Julia Stair Gouffon

Doctoral Dissertations

Epigenetic modifications serve as a means of intermediate gene expression control and nutritional inputs may modify methylation patterns in regulatory regions of genes. Therefore, we proposed that specific nutrient availability of folate affects adipocyte development and metabolism through impacting the one-carbon cycle and subsequent DNA methylation patterns. Accordingly, we sought to determine if the methylation level of CpG islands could be influenced in adipocytes and if so, how this might affect gene signaling in mature adipocytes. We treated adipocytes with 0 to 0.9 millimolar [mM] folate, the methyl donor S-adenosylmethionine (SAMe) and the methylation inhibitor, 5-aza-2-deoxycitidine (2-DC) both during adipocyte …

Distress Tolerance, Experiential Avoidance, And Negative Affect: Implications For Understanding Eating Behavior And Bmi, Christen Nicole Mullane

Doctoral Dissertations

Distress tolerance and experiential avoidance are important aspects of the coping process. In the current study, both were examined in relation to Body Mass Index and self-reported disturbances in mood and eating behavior. Distress tolerance was measured behaviorally and via self-report to elucidate the manner in which a) the ability to tolerate emotional distress, and b) the ability to persist behaviorally in the presence of stress-inducing stimuli were related to self-reported levels of depression, anxiety, maladaptive eating habits, and bodily concerns. A sample of 73 undergraduate students participated, and height, weight, and waist circumference were measured. Increased experiential avoidance was …

Genetic And Nutritional Studies To Elucidate The Role Of Adipose Tissue In The Pathogenesis Of Metabolic Syndrome, Nishan Sudheera Kalupahana

Doctoral Dissertations

Obesity is a major health problem in the United States and worldwide. It increases the risk for type-2 diabetes and cardiovascular diseases. A chronic low-grade inflammation occurring in white adipose tissue (WAT) is causally linked to the development of insulin resistance (IR), metabolic syndrome and obesity-associated chronic diseases. The aim of this dissertation research was to elucidate the WAT function in metabolic syndrome using genetic (overexpression of an adipose pro-inflammatory hormone, angiotensinogen) and nutritional manipulations/approaches (caloric restriction and omega-3 fatty acids), with specific emphasis on the role of inflammation.

Previous research indicates that WAT renin-angiotensin system (RAS) is overactivated in …

An Eating Frequency Prescription For A Behavioral Weight Loss Intervention, Jessica Lynne Bachman

Doctoral Dissertations

Improved weight loss interventions are needed to help reduce obesity. One dietary factor that has been effective in increasing weight loss is increased dietary structure. One method for increasing dietary structure is prescribing the frequency in which eating bouts (meals and snacks) occur. Eating frequency (EF) has been inversely related to body mass index (BMI) but the impact of EF on weight loss is unclear. This randomized controlled trial examined the effect of EF on hunger, the relative-reinforcing value of food, energy intake (EI), and weight loss during a 6 month behavioral weight loss intervention. Participants (age: 51.0 ± 9.9 …

Mechanisms Associated With The Chemotherapeutic Effects Of Zyflamend, A Multi-Herbal Extract, On Advanced Prostate Cancer, E-Chu Huang

Doctoral Dissertations

Advanced prostate cancer (PrC) is the second leading cause of death from cancer in US males. Advanced PrC cells are initially androgen-sensitive and thus androgen ablation therapy causes tumors to undergo regression and fall into a remission phase where residual cells remain dormant while androgen levels remain very low. Unfortunately, this phase usually lasts 3 to 5 years prior to tumor relapse, where the tumor cells re-grow in the absence of androgens. This form of the disease is aggressive and invariably fatal. In this study, we investigated the effects of a combination of herbal extracts on various stages of PrC, …

Role Of Dietary Calcium And Dairy In Modulating Oxidative Stress, Inflammatory Stress And Lifespan, Antje Eerenstein Bruckbauer

Doctoral Dissertations

Oxidative stress and inflammatory stress have been implicated as a cause of tissue damage in multiple organ systems, leading to the development of chronic diseases such as obesity, diabetes, hypertony and atherosclerosis. They are also recognized as major factors contributing to the physiological process of aging. Previous studies have demonstrated that dietary calcium regulates reactive oxygen species production (ROS) production in adipocytes in vitro and in vivo, and inhibits adipocyte-derived inflammatory cytokine expression by suppression of calcitriol. In addition, high calcium diets modulate energy metabolism and partitioning between adipose tissue and muscle resulting in a decrease in fat storage and …

Development Of A Mathematical Model That Will Predict The Mean Daily Dietary Intake Of Pregnant Women Based Upon Sociological, Psychological And Physiological Factors Assumed To Be Related To The Mean Daily Dietary Iron Intake, Waneen Ann Liudahl

Doctoral Dissertations

The purpose of this investigation was to develop a mathematical model using linear stepwise regression analysis that would predict the dietary iron intake of pregnant women. Development of the mathematical model was based upon sociological, psychological and physiological factors assumed to be related to the dietary iron intake of pregnant women.

Fifty-seven pregnant women participated in the study. They were private outpatients of two obstetricians at the Macomb Clinic, Macomb, Illinois.

The dependent variable used in the development of the models was the seven-day mean daily dietary iron intake for each pregnant woman which was obtained during the second and/or …

Influence Of Diet And Feed Restriction On Kidney Function In Aging Male Rats, Sarah May Tucker

Doctoral Dissertations

The influence of diet and feed restriction on kidney function was studied in aging male albino rats. Rats were fed either a commercial feed (LB) or a modified human diet (MHD) from weaning until sacrifice at either 12 or 24 months of age. Animals sacrificed at 12 months of age were either restricted or fed LB ad libitum from 1 month of age until sacrifice. Animals fed LB and sacrificed at 24 months of age were restricted for one of the following intervals: A, no restriction; R, restriction from 1 month to 12 months; AR, restriction from 12 to 24 …

The Effects Of Dietary Supplements On Bone Density And Nutritional Status Of Elderly Women, Glenda Sue Thompson

Doctoral Dissertations

Seventy-six ambulatory women with a mean age of 68 years participated in a 12-month study of the effects of fluoride, with and without multivitamin and calcium phosphate supplements, on nutritional status including bone density. Mean daily nutrient intakes calculated from 4- to 7-day weighed food intakes were 15 19 kcal including 15% from protein and 36% from fat; others were 797 mg calcium, 1000 mg phosphorus, and 8.6 mg iron. Mean intakes by 59 women who were not receiving vitamin supplements were 5800 IU of vitamin A and 35 mg of ascorbic acid. Mean blood hemoglobin was 13.9 g/100 ml; …

Isolation And Characterization Of A High Energy Iron-Sulfur Protein From Mammalian Cells, Beth Feland

Doctoral Dissertations

A sulfur-containing protein (S-protein) was proposed to be an intermediate in the sulfation of cellular constituents containing ester sulfate after it was observed that S-protein isolated from the particulate fraction of the cell was unaffected by avitaminosis E, the stress of malathion intoxication or the level of inorganic sulfate in the diet. The present investigation was undertaken in an attempt to identify the cellular role of the S-protein in sulfate utilization.

The role of the S-protein as a possible intermediate in the sulfation of ester sulfates was determined using both a natural sulfate acceptor, mucopolysaccharide, and an artificial sulfate acceptor, …