Life Sciences Commons^™

Gpr75 Deficiency Attenuates High Fat Diet-Driven Obesity And Glucose Intolerance, Sakib Hossain

NYMC Student Theses and Dissertations

Recently, a collaboration between Regeneron Pharmaceuticals and the Schwartzman-Garcia labs at New York Medical College published an exome sequencing study of individuals across the United Kingdom, United States, and Mexico which concluded that individuals possessing non-functioning, truncated mutations to the orphan g protein coupled receptor (GPCR), GPR75, had lower BMI and 54% reduced likelihood of obesity. The present study was undertaken to fully characterize the metabolic phenotype of Gpr75 deficient mice when fed a high fat diet (HFD) and explore potential mechanisms by which GPR75 activation links to increased adiposity and decreased glucose tolerance. After 14 weeks of HFD-feeding we …

The Exposome, Metabolic Dysfunction And Silicosis: A Pulmonary And Pathophysiology Study, Janet A. Thompson

Graduate Theses, Dissertations, and Problem Reports

The exposome encompasses the concept that an individual’s health is a combination of genetic, environmental, and occupational exposures. A worker’s exposomal profile could potentially influence their susceptibility to hazardous occupational exposures. Over 35% of adults in the United States have metabolic dysfunction (MetDys), yet interactions between MetDys and hazardous occupational exposures are generally unknown. MetDys is associated with HFWD-consumption and obesity and induces a chronic low grade systemic inflammation and alters serum adipokine profiles. Silicosis, a progressive inflammatory lung disease, results from occupational inhalation exposure to respirable crystalline silica particles. This research tests the hypothesis “Inflammation resulting from HFWD-induced …

Scaling Of Computed Tomography Body Composition To Height: Relevance Of Height-Normalized Indices In Patients With Colorectal Cancer, Justin C. Brown, Steven B. Heymsfield, Bette J. Caan

School of Medicine Faculty Publications

Background: Body weight scales to height with a power of ≈2 (weight/height2), forming the basis of body mass index (BMI). The corresponding scaling of body composition measured by abdominal computed tomography (CT) to height has not been established. The objective of this analysis was to quantify the scaling of body composition measured by a single-slice axial abdominal CT image (skeletal muscle, and visceral, subcutaneous, and total adipose tissue) to height in patients with colorectal cancer (CRC). Methods: This cross-sectional study included non-Hispanic white males and females, aged 18–80 years, who were diagnosed with stage I–III CRC at an integrated health …

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 …

Examining The Effects Of Interleukin-6 On Appetite Regulatory Peptides In Lean And Obese Sedentary Males, Greg L. Mckie

Theses and Dissertations (Comprehensive)

Acute moderate-intensity exercise transiently suppresses appetite via fluctuations in the appetite-regulatory peptides acylated ghrelin (AG), peptide tyrosine-tyrosine_3-36 (PYY_3-36), and active glucagon-like peptide-1 (GLP-1). Importantly, these effects do not lead to compensatory changes in energy intake in normal weight or obese individuals, highlighting the potential for exercise to induce acute energy deficits. One potential mechanism for these effects is increased post-exercise plasma concentrations of interleukin (IL)-6, as IL-6 has demonstrated appetite-inhibitory effects in animal and cell culture models. Given obesity is characterized by a state of chronic low-grade inflammation and associated with upregulated IL-6, this study sought to …

High-Fat Feeding Does Not Disrupt Daily Rhythms In Female Mice Because Of Protection By Ovarian Hormones, Brian T. Palmisano, John M. Stafford, Julie S. Pendergast

Biology Faculty Publications

Obesity in women is increased by the loss of circulating estrogen after menopause. Shift work, which disrupts circadian rhythms, also increases the risk for obesity. It is not known whether ovarian hormones interact with the circadian system to protect females from obesity. During high-fat feeding, male C57BL/6J mice develop profound obesity and disruption of daily rhythms. Since C57BL/6J female mice did not develop diet-induced obesity (during 8 weeks of high-fat feeding), we first determined if daily rhythms in female mice were resistant to disruption from high-fat diet. We fed female PERIOD2:LUCIFERASE mice 45% high-fat diet for 1 week and measured …

Assessing For Awareness And Knowledge Regarding Diabetes In Pre-Diabetes Obese Patients, Remona Lysa Brown

Walden Dissertations and Doctoral Studies

Over the past few decades, there has been an increase in prevalence of diabetes in the United States. Prevention of diabetes and improving patients' knowledge and awareness of diabetes are crucial for healthcare providers. Using the Health Belief Model (HBM) as a theoretical foundation, the student used the National Diabetes Prevention Program (NDPP) from the Centers for Disease Control and Prevention (CDC), to improve awareness and knowledge of diabetes among obese individuals with prediabetes. The key research question of this project was to determine whether the patients' diabetes knowledge and awareness improved after the NDPP program. A convenience sample of …

Restraint Stress Alters Pro-Inflammatory Cytokine Expression And Increases Superoxide Dismutase In The Rat Hypothalamus And Hippocampus, Kristina Isabel Barron

Open Access Theses & Dissertations

The impact of restraint stress on changes in cytokine expression and oxidative stress markers in hippocampal (Hipp) and hypothalamic (Hyp) regions of the brain, were assessed in a rat model. In addition, immune and inflammatory variables were assessed in peripheral blood. Male Wistar rats were acutely (30 min) or repeatedly (30 min/d for 14 consecutive days) exposed to a restraint stress, or maintained as non-stressed controls. At the time of sacrifice, whole blood and brain tissues enriched in Hyp or Hipp regions were collected; blood was collected with EDTA as an anticoagulant and centrifuged to yield plasma. All tissue samples …

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …

Fatty Acid Fate In Determining Oxidation And Inflammation In Adipose Tissue, Emilio Patrick Mottillo

Wayne State University Dissertations

Adipose tissue (AT) is a critical regulator of energy balance through its ability to store or oxidize free fatty acids (FFAs). White adipose tissue (WAT) functions as an anabolic organ to sequester and release FAs, in contrast brown adipose tissue (BAT) is a catabolic organ that oxidizes FAs. However, a comprehensive understanding of the role that FFAs play in the function of WAT and BAT is needed. Here we demonstrate that intracellular FAs enhance the expression of inflammatory cytokines by β3-AR activation in adipocytes, in which the expression of PAI-1 is partly mediated by the de novo synthesis of ceramides/sphingolipids. …

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 …