Nutritional and Metabolic Diseases Commons^™

Characterizing Aft1/2-Grx3/4 Interaction And The Role Of Bol2 During Iron Regulation In Saccharomyces Cerevisiae, William Rivers

Senior Theses

Iron dysregulation has been linked to a variety of human diseases, such as anemia, Friedreich’s ataxia, X-linked sideroblastic anemia, sideroblastic-like microcytic anemia, and myopathy. Thus, it is vitally important to understand the mechanisms for regulating intracellular iron. Here, we use fluorescence microscopy techniques in live cells to study interactions of the yeast proteins Grx3/4, Aft1/2, and Bol2, which have been shown to be involved in turning off iron import when the cell has adequate iron. Modified versions of genes encoding these proteins have been incorporated into several yeast backgrounds to use fluorescence to monitor interactions under varying iron levels.

Innovation And Competition In Advanced Therapy Medicinal Products, Enrique Seoane-Vazquez, Vaishali Shukla, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

"Advanced therapy medicinal products (ATMPs), including gene therapy, cell therapy, and tissue engineering products, represent a paradigm shift in health care as they have great potential for preventing and treating many diseases (Food and Drug Administration (FDA), 2013). By way of example, only 367 (8.0%) of the 4,603 rare diseases and conditions listed by the NIH Genetic and Rare Diseases Information Center had at least one FDA-approved drug therapy in early 2018. An estimated 3,038 (66.0%) of those rare diseases and conditions are congenital and genetic diseases that could potentially be treated by gene therapy. There are already ATMPs under …

Autoimmune Hyperphosphatemic Tumoral Calcinosis In A Patient With Fgf23 Autoantibodies., Mary Scott Roberts, Peter D. Burbelo, Daniela Egli-Spichtig, Farzana Perwad, Christopher J. Romero, Shoji Ichikawa, Emily G. Farrow, Michael J. Econs, Lori C. Guthrie, Michael T. Collins, Rachel I. Gafni

Manuscripts, Articles, Book Chapters and Other Papers

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 …

Epidermal Growth Factor Receptor (Egfr) Inhibition By Polychlorinated Biphenyls Contributes To Non-Alcoholic Fatty Liver Disease (Nafld)., Josiah Hardesty

Electronic Theses and Dissertations

This dissertation describes how poly-chlorinated biphenyls (PCBs) exacerbate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). While PCBs were banned in 1979, they still persist in contaminated biota, including food, and are detected in human plasma and adipose. The body burden of PCBs is associated with elevation of liver enzymes and necrosis markers in humans, characteristic of NAFLD. PCB exposure in high-fat diet fed mice leads to steatohepatitis that recapitulate the findings seen in exposed humans. The global estimate of people diagnosed with NAFLD is up to 1 in 4 people, unrelated to dietary or genetic factors. The hepatic mechanisms …

Evaluation Of Endothelial Cell Responses To Elevated Glucose, Gabriella Sugerman

Master's Theses

Developing a tissue-engineered Blood Vessel Mimic (BVM) to represent diabetic macrovascular disease could expedite design of new vascular devices specifically tailored to diabetic patients. In contribution toward this model, this thesis assessed Human Umbilical Vein Endothelial Cell (HUVEC) responses to high glucose conditions. Interleukin 6 (IL-6) and Cluster of Differentiation 36 (CD36) were selected to signify oxidative stress activity, a hallmark of diabetic macrovascular disease. Next, activity of potential reference genes B2M, HPRT1, and ACTB was assessed. All genes were found to exceed acceptable variability, so the E-ΔC T method of data analysis was selected. Next, cellular responses to high …

Loss Of Marv1 Promotes Chop Signaling In Mouse Liver, Shad Anthony Mitchell

Graduate School of Biomedical Sciences Theses and Dissertations

Metabolic syndrome (MetS) is a term used to define a set of metabolic diseases: obesity, type 2 diabetes (T2D), hyperlipidemia, hypertension, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic hepatosteatosis (NASH). Those with MetS have a higher incidence of cardiovascular disease and stroke. Current drug treatments for MetS treat the individual pathologies associated with the diseases, rather than directly targeting MetS as a whole. We hypothesize that the inhibition of a ubiquitous lipid transporter known as ARV1 can improve pathologies associated with MetS. To test this hypothesis, we utilized liver tissue from mARV1 knockout mice fed a high-fat diet and examined …

Apoe And Alzheimer’S Disease: Neuroimaging Of Metabolic And Cerebrovascular Dysfunction, Jason A. Brandon, Brandon C. Farmer, Holden C. Williams, Lance A. Johnson

Physiology Faculty Publications

Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for late onset Alzheimer’s Disease (AD), and is associated with impairments in cerebral metabolism and cerebrovascular function. A substantial body of literature now points to E4 as a driver of multiple impairments seen in AD, including blunted brain insulin signaling, mismanagement of brain cholesterol and fatty acids, reductions in blood brain barrier (BBB) integrity, and decreased cerebral glucose uptake. Various neuroimaging techniques, in particular positron emission topography (PET) and magnetic resonance imaging (MRI), have been instrumental in characterizing these metabolic and vascular deficits associated with this important AD risk factor. In …

Dietary Habits And Lifestyle In School-Aged Children From Bucharest, Romania, Anca Pantea Stoian, Liliana F. Andronache, Razvan Hainarosie, Dan N. Paduraru, Cristinel D. Badiu, Andreea Arsene, Claudia Mehedintu, Georgiana Ditu, Silviu M. Pituru, Cristina Orlov, Mihaela Oros, Cornelia Nitipir

Journal of Mind and Medical Sciences

Background. This study evaluated the difference between boys and girls in terms of nutritional status, lifestyle, and dietary habits during school life.

Materials and Methods. A descriptive and observational study was conducted in 2016, in which 251 children, aged 7-17, from 3 elementary schools and a high school inBucharest,Romania, were evaluated. A questionnaire was used to assess food behavior, eating, and lifestyle habits.

Results. Boys had a significantly higher waist circumference (71.18±9) than girls (67.46±9.91) (p=0.004). Thus 27% of boys were overweight or obese compared with only 22% of the girls. Differences were also seen between the two groups in …

Role Of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-Sdkp) And Renal Hemodynamics On Obesity Related Renal Damage, Mani Maheshwari

Theses, Dissertations and Capstones

Obesity is a public health problem and is associated with salt-sensitive hypertension, kidney inflammation and fibrosis. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a tetra-peptide with anti-inflammatory and anti-fibrotic properties but its effect on kidney damage in obesity is unknown. We hypothesized that high salt fed Zucker obese (ZO) rats develop renal damage, inflammation and fibrosis and that Ac-SDKP prevents these changes. Zucker lean (ZL) rats served as controls. Animals were treated with Ac-SDKP while maintained on either a normal-salt or HS diet for 8 weeks. Systolic blood pressure (SBP), albuminuria, renal inflammation and fibrosis were evaluated. HS diet increased macrophage infiltration in the …

Effect Of Empagliflozin On Insulin Sensitivity In The Lean And Obese Zucker Rat: A Model Of Metabolic Syndrome, Veda Gayatri Sushma Penta

Theses, Dissertations and Capstones

Metabolic syndrome is one of the fastest growing health problems in the world. The medical costs associated with treating this disorder are staggering. Allowed to proceed untreated, metabolic syndrome can lead to a markedly decreased quality of life and a variety of medical conditions including heart and kidney failure. Whether the sodium glucose co-transporter-2 (SGLT-2) inhibitor Empagliflozin can be used to prevent the development of metabolic syndrome is not well understood. This proposal is specifically designed to address this gap in our knowledge. The expected outcomes of this work will identify the time course and degree of interrelatedness between changes …

Comparative Effectiveness And Safety Of Empagliflozin On Cardiovascular Mortality And Morbidity In Adults With Type 2 Diabetes, Wilbert S. Aronow, Tatyana Shamliyan

NYMC Faculty Publications

Background: Based on a single placebo-controlled randomized clinical trial, empagliflozin is licensed to reduce cardiovascular death in diabetes and comorbid cardiovascular disease. Methods: We examined the comparative effectiveness of empagliflozin on mortality and cardiovascular morbidity in type 2 diabetes. We conducted random-effects direct frequentist meta-analyses of aggregate data and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our search in PubMed, EMBASE, the Cochrane Library, clinicaltrials.gov, and PharmaPendium up to May 2017 identified 11 meta-analyses, multiple publications, and unpublished data from 29 randomized controlled trials (RCTs). Results: Empagliflozin reduces all-cause mortality [relative …

Optimizing Heart Failure Outcomes Through Diet: A Review, Farley B. Neasman Iii

Marshall Journal of Medicine

Heart failure is a growing epidemic that will add significant monetary and human costs to an already overtaxed health-care system. Though promising new medications have recently been approved, this complex condition is largely preventable through aggressive risk factor modification, with diet being shown to have a greater effect than exercise. An underrated component of a healthy diet is the simple addition of nuts – the anti-inflammatory fatty acids, healthy proteins, and general availability have been shown to improve survival and reduce the primary risk factors contributing to heart failure, making the addition of nuts and legumes to the diet an …

A Functional Algorithm For Weight Loss And Obesity Practice: Guide For Clinical Decision-Making For Treating Women, Jennifer A. Tice Williams

Dissertations

ABSTRACT

Background

Overweight and obesity have significant impact and consequences on women leading to reduced quality of life, comorbid conditions and premature mortality. Many healthcare providers lack adequate training and the time to properly treat overweight and obesity. Algorithms have been shown to improve clinical knowledge and save time.

Objectives

To develop an algorithm for weight loss assessment and treatment to aid in the clinical decision-making process while improving the quality of care for overweight and obese clients in an efficient manner that can be replicated.

Methods

After an extensive literature review to identify best-practice guidelines for weight loss a …

Sex-Dependent Effects Of Ho-1 Deletion From Adipocytes In Mice, Peter A. Hosick, Mary Frances Weeks, Michael W. Hankins, Kyle H. Moore, David E. Stec

Department of Exercise Science and Physical Education Scholarship and Creative Works

Induction of heme oxygenase-1 (HO-1) has been demonstrated to decrease body weight and improve insulin sensitivity in several models of obesity in rodents. To further study the role of HO-1 in adipose tissue, we created an adipose-specific HO-1 knockout mouse model. Male and female mice were fed either a control or a high-fat diet for 30 weeks. Body weights were measured weekly and body composition, fasting blood glucose and insulin levels were determined every six weeks. Adipocyte-specific knockout of HO-1 had no significant effect on body weight in mice fed a high-fat diet but increased body weight in female mice …

Emerging Roles Of Xenobiotic Detoxification Enzymes In Metabolic Diseases, Michael C. Petriello, Jessie B. Hoffman, Andrew J. Morris, Bernhard Hennig

Superfund Research Center Faculty Publications

Mammalian systems have developed extensive molecular mechanisms to protect against the toxicity of many exogenous xenobiotic compounds. Interestingly, many detoxification enzymes, including cytochrome P450s and flavin-containing monooxygenases, and their associated transcriptional activators [e.g. the aryl hydrocarbon receptor (AhR)], have now been shown to have endogenous roles in normal physiology and the pathology of metabolic diseases. This mini-review will focus on two such instances: the role of flavin-containing monooxygenase 3 (FMO3) in the formation of the cardiometabolic disease biomarker trimethylamine-N-oxide (TMAO) and the role of AhR as a sensor of endogenous ligands such as those generated by the gut microbiota. Understanding …

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. …

Evaluation Of A Diabetes Self-Management Program For Hispanics In Lexington Kentucky: A Pilot Study, Miguel A. Gamboa Oropeza

Theses and Dissertations--Nutrition and Food Systems

Hispanics are more affected by diabetes than non-Hispanic whites and they tend to experience more severe complications. Research shows that although self-management is poor among ethnic minorities, it is even more so among Hispanics. The “Taking Ownership of Your Diabetes” (TOYD) program has been shown to be successful in helping individuals manage their diabetes. However, no work has been conducted with Hispanic audiences in Kentucky. TOYD program allows individuals to modify lifestyle risks and solve problems related to diabetes management. The program was translated from English to Spanish. Hispanics males and females between ages 19 to 75 years …

Effects Of Nox-1 Inhibition On Real-Time Blood Nitric Oxide And Hydrogen Peroxide In Acute Hyperglycemia, Ashley Mawhinney

PCOM Biomedical Studies Student Scholarship

Hyperglycemia has been associated with vascular endothelial dysfunction in part by a reduction in nitric oxide (NO) production and increased oxidative stress (e.g., increased superoxide (SO) and hydrogen peroxide (H₂O₂). Endothelial-derived NO can be significantly reduced by increased SO/H₂O₂ in part by the activation of NADPH oxidase during hyperglycemia. Of the 7 NADPH oxidase isoforms, NADPH oxidase isoform 1 (NOX1) is mainly expressed in the vasculature and may play a major role in hyperglycemia induced oxidative stress and vascular endothelial dysfunction. This hypothesis was tested by measuring blood NO and H2O2 levels in …

Modulation Of Body Weight By Intestinal Flora In Orphan Nuclear Receptor Shp-/- Mice, Ryan Mifflin

Williams Honors College, Honors Research Projects

The whole-body deletion of small heterodimer partner (SHP) in mice is associated with protection from diet-induced obesity and hepatic steatosis upon feeding of a western diet. This protection was reported to be mediated through decreases in hepatic gene expression for lipogenesis, as well as increases in gene expression for fatty acid oxidation. SHP has been known to regulate the expression of the CYP7A1 gene, encoding the rate-limiting enzyme for bile acid synthesis, thereby altering the bile acid pool. The effects of this altered bile acid profile on the gut microbiome are unknown, as some bacteria in the gut are responsible …

Mechanisms By Which Dietary Ellagic Acid Attenuates Obesity And Obesity-Mediated Metabolic Complications, Inhae Kang

College of Education and Human Sciences: Dissertations, Theses, and Student Research

Ellagic acid (EA) is a polyphenol found in various fruits and plants, such as berries, pomegranates, muscadine grapes, nuts and bark of oak tree. EA has been known to exhibit anti-inflammatory and anti-proliferative effects in various types of cancer. However, little is known about the effects of EA on obesity. Herein, 1) the lipid-lowering role of EA was identified in primary human adipose stem cells (hASCs) and human hepatoma Huh7 cells; 2) the molecular mechanisms by which EA attenuates adipogenesis by epigenetic modification were identified; 3) the effects of EA on high fat and high sucrose-mediated obesity was …

Raising Awareness: Polycystic Kidney Disease, Dana Dendinger

Nursing Student Class Projects (Formerly MSN)

A young male patient was recently admitted to the intensive care unit at a local hospital with hypertensive urgency and acute renal failure of unknown etiology. A renal ultrasound showed polycystic kidneys and upon further investigation, it was discovered that the patient’s mother passed away last year from end stage renal failure related to polycystic kidney disease (PKD). The aforementioned case and the recent study into inherited disorders are what prompted further investigation into PKD. Liebau and Serra (2013) explain that “inherited cystic kidney diseases, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD), are the …

Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance In High Fat-Fed Mice, Michelle B. Trevino, David Mazur-Hart, Yui Machida, Timothy King, Joseph Nadler, Elena V. Galkina, Arjun Poddar, Sucharita Dutta, Yumi Imai

Mathematics & Statistics Faculty Publications

Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid classes, …

Basics Of Oncologic Type B Lactic Acidosis: Increased Awareness For Better Outcomes?, Erin E. Steiner

Nursing Student Class Projects (Formerly MSN)

The most common and best known form of lactic acidosis, Type A, presents in the environment of tissue hypoxia. The lesser known form, Type B, does not involve tissue hypoxia, is not well understood, and very often results in death. No randomized controlled trials (RCTs) comparing treatment modalities currently exist (Ruiz, Singh, & Hart, 2011). Increased recognition by medical and nursing disciplines may result in quicker diagnosis, opportunity to implement treatment, possibility for RCTs, and better outcomes.

Inborn Error Of Metabolism Is A Disease Of Any Age; Carniting Palmitoyltransferase Ii Deficiency And Its Manifestations, Mira Mitry Md, James Ross Md, Facp

Department of Medicine

No abstract provided.

Associations Between Alcohol Consumption And Fasting Blood Glucose In Young Adults, Julie Ann Lucca

Master's Theses

Current research shows moderate alcohol consumption is associated with decreased risk of diabetes and excessive consumption or binge drinking can cause insulin resistance and diabetes. In 2010, diabetes was the seventh leading cause of death in the United Statesand was responsible for significant health complications: blindness, kidney failure, and limb amputations, and is a large national economic burden. Fasting blood glucose (FBG) is a tool used to help diagnose diabetes. Abnormally high FBG, ≥100 mg/dl, is indicative of diabetes and pre-diabetes. Few studies have observed diabetic prevalence among young adults or college students. Studying young adults can help provide added …

Eating Behaviors Of Older Adults Participating In Government-Sponsored Programs With Different Demographic Backgrounds, Yeon Bai, Shahla M. Wunderlich, Joseph Brusca, Johnson-Austin Marti, Michelle O'Malley

Department of Nutrition and Food Studies Scholarship and Creative Works

The purpose of this study was to determine the food behaviors of nutritionally high-risk seniors as a function of their racial background, gender, marital status, and education level. A total of 69 seniors were identified to be at high nutritional risk using the Nutrition Screening Initiative (NSI) checklist. A supplemental questionnaire (SQ) was created to examine the risk factors in relation to the participant’s demographic background. Key results indicated that Asians practiced healthy food behaviors and women were more likely to eat alone (p≤0.05). Married participants (90.9%) were most likely to consume 2 meals or more each day. College educated …

Post Gastric Bypass Hypoglycemia: Four Cases Treated Successfully With Alphaglucosidase Inhibitor Therapy, Shavon S. Frankhouser Do, Aakif N. Ahmad Do, Gretchen A. Perilli Md, Benjamin J. Quintana Md, Marc A. Vengrove Do, Facp

Department of Medicine

No abstract provided.

The Effects Of Curcumin On Body Composition Of Patients With Advanced Pancreatic Cancer, Henrique A. Parsons Md

Dissertations and Theses (Open Access)

Cachexia is very common among patients with advanced pancreatic cancer and is a marker of poor prognosis. Weight loss in cachexia is due to both adipose and muscle compartments, and sarcopenia (severe muscle depletion) is associated with worse outcomes. Curcumin has shown a myriad of biological effects, including anti-cancer and anti-inflammatory. The ability of curcumin to attenuate cachexia and muscle loss has been tested in animal models, with conflicting results so far. The hypothesis of this study was that patients with advanced pancreatic cancer treated with curcumin for two months have less fat and muscle loss as compared to matched …

Probiotic Therapy - Recruiting Old Friends To Fight New Foes, Roy D. Sleator

Department of Biological Sciences Publications

Against a backdrop of increasing antibiotic resistance, and the emergence of new and evolving pathogens, clinicians are increasingly forced to consider alternative therapies - probiotics are one such alternative.

Diabetes Alters Contraction-Induced Mitogen Activated Protein Kinase Activation In The Rat Soleus And Plantaris, Anjaiah Katta, Deborah L. Preston, Sunil K. Kakarla, Shinichi Asano, Sarath Meduru, Sriram P. Mupparaju, Ellie Yokochi, Kevin M. Rice, Devashish H. Desai, Eric R. Blough

MIIR Faculty Research

The prescription of anaerobic exercise has recently been advocated for the management of diabetes; however exercise-induced signaling in diabetic muscle remains largely unexplored. Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. Here, we compare the basal and the in situ contraction-induced phosphorylation of Erk1/2- p38- and Jnk-MAPK and their downstream targets (p90rsk and MAPKAP-K2) in the plantaris and soleus muscles of normal and obese (fa/fa) Zucker rats. Compared to lean animals, the time course and magnitude of Erk1/2, p90rsk and …