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 …

(Pro)Renin Receptor And Its Soluble Form In Metabolic Dysfunction: Friend Or Foe?, Gertrude Arthur

Journal of Pharmacology & Nutritional Sciences

(Pro)renin receptor is component of the renin angiotensin system which has been shown to be involved in several physiological and pathophysiological processes including blood pressure regulation and hypertension, water and electrolyte balance, kidney injury, obesity, and metabolic dysfunction. Enzymatic cleavage of prorenin receptor produces soluble prorenin receptor which can also activate the renin angiotensin system stimulate similar pathophysiological process like its full form receptor. This review explores findings on the role of prorenin receptor and soluble prorenin receptor in metabolic dysfunction and discusses the conflicting findings on soluble prorenin receptor in metabolic dysfunction.

Promoting Healthier Treatment Outcomes In Obese Cancer Patients Taking High Dose Methotrexate, Carly Dell'ova

Walden Dissertations and Doctoral Studies

Cancer and obesity rates continue to rise, creating enormous public heath burdens to the individual and at the national and global levels, reducing quality of life, and increasing spending. Moreover, the relationships between cancer and obesity are not well understood. A commonly used chemotherapy for several types of cancer is high dose methotrexate (HDMTX). Along with chemotherapy, especially at high doses, comes toxicity to specific organs and the entire body. However, limited research has been conducted on obese cancer patients as they are often excluded from clinical studies. Practitioners need to better understand how to dose these patients to provide …

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany B. Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Human Movement Sciences & Special Education Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal …

A Review Of Covid-19 In Relation To Metabolic Syndrome: Obesity, Hypertension, Diabetes, And Dyslipidemia, Elias Makhoul, Joseph L. Aklinski, Jesse Miller, Cara Leonard, Sean Backer, Payal Kahar, Mayur S. Parmar, Deepesh Khanna

HPD Articles

Although severe cases and mortality of coronavirus disease 2019 (COVID-19) are proportionally infrequent, these cases are strongly linked to patients with conditions of metabolic syndrome (obesity, hypertension, diabetes, and dyslipidemia). However, the pathophysiology of COVID-19 in relation to metabolic syndrome is not well understood. Thus, the goal of this secondary literature review was to examine the relationship between severe acute respiratory syndrome (SARS-CoV-2) infection and the individual conditions of metabolic syndrome. The objective of this secondary literature review was achieved by examining primary studies, case studies, and other secondary studies, to obtain a comprehensive perspective of theories and observations of …

Interactions Between Soft Nanoparticles And Mammalian Cells, Mitchell Raith

Doctoral Dissertations

Nanoparticles have been of interest to the pharmaceutical industry since the 1980s. The first FDA approved nanoparticle-based therapies included liposomal anesthesia agents. Since then, the amount of FDA-approved nanoparticle therapies remains low. This is because nanoparticle-patient interactions can be very complex and are not well understood. Complicating factors also include increasing obesity rates among the patient population and many small animal pre-clinical trials are completed with healthy, lean animals. The biochemical differences between lean and obese patients prevents early studies from accurately predicting nanoparticle clinical behaviors. Many nanoparticles fail in trails. In this thesis, I aimed to uncover how nanoparticles …

Ulva Prolifera Polysaccharide Exerts Anti-Obesity Effects Via Upregulation Of Adiponectin Expression And Gut Microbiota Modulation In High-Fat Diet-Fed C57bl/6 Mice, Hai-Ching Pung, Wei-Sheng Lin, Yi-Chen Lo, Cheng-Chih Hsu, Chi-Tang Ho, Min-Hsiung Pan

Journal of Food and Drug Analysis

Obesity is characterized by metabolic disorder and accompanying an altered and less diverse gut microbiota composition during a fat-enriched diet. Recent studies indicated that sulphated polysaccharide prevents high-fat diet (HFD) induced obesity, reduces metabolic disorder, and restores the gut microbiota. However, there are few studies about Ulva prolifera polysaccharide (UPP) may induce anti-obesogenic effects. Therefore, the present study investigates the enzymatic extracted UPP effects in HFD-fed mice. The results showed that UPP considerably slowed down the HFD-induced weight gain and improved metabolic disorders in HFD-fed mice. Notably, the effects were associated with lower body weight gain, reduced adipose tissue hypertrophy, …

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 …

Adipose-Specific Pparα Knockout Mice Have Increased Lipogenesis By Pask–Srebp1 Signaling And A Polarity Shift To Inflammatory Macrophages In White Adipose Tissue, Terry D. Hinds, Jr., Zachary A. Kipp, Mei Xu, Frederique B. Yiannikouris, Andrew J. Morris, Donald F. Stec, Walter Wahli, David E. Stec

Pharmacology and Nutritional Sciences Faculty Publications

The nuclear receptor PPARα is associated with reducing adiposity, especially in the liver, where it transactivates genes for β-oxidation. Contrarily, the function of PPARα in extrahepatic tissues is less known. Therefore, we established the first adipose-specific PPARα knockout (Ppara^FatKO) mice to determine the signaling position of PPARα in adipose tissue expansion that occurs during the development of obesity. To assess the function of PPARα in adiposity, female and male mice were placed on a high-fat diet (HFD) or normal chow for 30 weeks. Only the male Ppara^FatKO animals had significantly more adiposity in the inguinal white …

Systematic Review Of Polyherbal Combinations Used In Metabolic Syndrome, Amber Hanif Palla, Faridah Amin, Bilqees Fatima, Arooj Shafiq, Najeeb Ur Rehman, Ikram Ul Haq, Anwar-Ul-Hassan Gilani

Department of Biological & Biomedical Sciences

Background: Metabolic syndrome (MetS) is a multifactorial disease, whose main stay of prevention and management is life-style modification which is difficult to attain. Combination of herbs have proven more efficacious in multi-targeted diseases, as compared to individual herbs owing to the "effect enhancing and side-effect neutralizing" properties of herbs, which forms the basis of polyherbal therapies This led us to review literature on the efficacy of herbal combinations in MetS.
Methods: Electronic search of literature was conducted by using Cinnahl, Pubmed central, Cochrane and Web of Science, whereas, Google scholar was used as secondary search tool. The key words used …

Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu

Theses and Dissertations--Pharmacy

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease. A T cell cytokine profile (Th17) from PBMCs can distinguish obese T2D from obese non-diabetes subjects. Individual T cell subsets interact with each other and the diverse subsets jointly determine overall inflammation. Cellular metabolism drives cytokine production of CD4⁺ T cells, and therefore contributes to inflammation in T2D. However, specific changes in metabolism and function of CD4⁺ T cells during the progression from lean healthy to obese and diabetic stages in people have not been clarified.

We hypothesize that human regulatory T cells (Treg) impact metabolism of effector …

Rats Genetically Selected For High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin By Upregulation Of Hepatic Biliverdin Reductase-A (Bvra) And Suppression Of Ugt1a1, Terry D. Hinds Jr., Justin F. Creeden, Darren M. Gordon, Adam C. Spegele, Steven L. Britton, Lauren G. Koch, David E. Stec

Pharmacology and Nutritional Sciences Faculty Publications

Exercise in humans and animals increases plasma bilirubin levels, but the mechanism by which this occurs is unknown. In the present study, we utilized rats genetically selected for high capacity running (HCR) and low capacity running (LCR) to determine pathways in the liver that aerobic exercise modifies to control plasma bilirubin. The HCR rats, compared to the LCR, exhibited significantly higher levels of plasma bilirubin and the hepatic enzyme that produces it, biliverdin reductase-A (BVRA). The HCR also had reduced expression of the glucuronyl hepatic enzyme UGT1A1, which lowers plasma bilirubin. Recently, bilirubin has been shown to activate the peroxisome …

The Potential Role Of Phenolic Compounds On Modulating Gut Microbiota In Obesity, Gow-Chin Yen, Hsin-Lin Cheng, Li-Yu Lin, Shiuan-Chih Chen, Chin Lin Hsu

Journal of Food and Drug Analysis

Obesity is a rising public health issue and challenge which is tightly correlated with socio-economic development paralleled with increased energy intake and sedentary behavior that subsequently cause adipose tissue accumulation. Physiological and metabolic status changes during obesity development have been suggested with low grade inflammation of gastrointestinal tract. The gut microbiota plays an essential role in regulating whole body energy metabolism and also lipid accumulation, and immunity of host. However, the detail mechanism of which the gut microbiota composition influence obesity development in humans still need deeper investigation owing to the complex pathophysiology of such disease. Recently, the consumption of …

Effects Of High Fat Diets, Esther Abady

The Science Journal of the Lander College of Arts and Sciences

With obesity on the rise, and subsequently numerous diseases, many people are looking for newer ways to counter the effects of the influx of fatty, high sugar and unhealthy foods they are consuming. The most common and widely used method is a diet plan. The key to both a healthy and effective diet is knowing what the diet does to the body. There are short term diets which have adverse effects if kept for too long and long-term diets which are aimed for a healthy lifestyle. Every diet is based on the increased and decreased consumption of different macronutrients and …

The Role Of Secretory Phospholipase A2 Group Iia In Obesity And Metabolism, Michael S. Kuefner

Theses and Dissertations (ETD)

Secretory phospholipase A2 group IIA (PLA2G2A) is a member of a family of secretory phospholipases previously implicated in inflammation, atherogenesis, and antibacterial actions. These enzymes hydrolyze glycerophospholipids at the sn-2 position releasing lysophospholipids and fatty acids. Though studies have shown PLA2G2A is pro-inflammatory and promotes atherosclerosis, no research has analyzed the role of this enzyme in obesity and metabolism. Studies in the past 5-10 years utilizing various knock- out or over-expression mouse models have analyzed the role of different secretory phospholipase A2s (sPLA2) in metabolic diseases. From these studies, it is known that at least seven of the 11 sPLA2 …

Are Health Problems In Adulthood Linked To Our Experiences In The Womb? An Epigenetic Approach, Simone Tendler

The Science Journal of the Lander College of Arts and Sciences

The origins of adult disease have been a prime topic for research, as deciphering causes can lead to strategies for preventions and cures. There has been recent intrigue focused on the environment in the womb. Records from England and Wales in 1911 show that those who suffered from cardiovascular disease were geographically correlated with regions high in infant mortality in the past, seventy years before the study. When looking into the cause of the neonatal death rates, low birth weight, poor maternal health, and high maternal death rates during childbirth were clearly associated. Barker inferred that there is much happening …

The Relationship Between Pcos And Obesity: Which Comes First?, Sara L. Rosenberg

The Science Journal of the Lander College of Arts and Sciences

Polycystic ovary syndrome (PCOS) is recognized as the most common reproductive disorder in women. Obesity is believed to play a central role in the development of PCOS, as many women with this condition are reported to be overweight or obese. A strong correlational relationship exists between PCOS and obesity. This paper examines the relationship between PCOS and obesity in order to determine whether PCOS causes obesity as opposed to obesity causes metabolic changes that lead to PCOS. Analysis was conducted by reviewing and comparing many studies related to the topic. Factors such as insulin resistance, hyperandrogenemia and body fat distribution …

Using Neonatal Skin To Study The Developmental Programming Of Aging, Leryn J. Reynolds, Brett J. Dickens, Benjamin B. Green, Carmen J. Marsit, Kevin J. Pearson

Pharmacology and Nutritional Sciences Faculty Publications

Numerous studies have examined how both negative and positive maternal exposures (environmental contaminants, nutrition, exercise, etc.) impact offspring risk for age-associated diseases such as obesity, type 2 diabetes, hypertension, and others. The purpose of this study was to introduce the foreskin as a novel model to examine developmental programming in human neonates, particularly in regard to adipogenesis and insulin receptor signaling, major contributors to age-associated diseases such as obesity and diabetes. Neonatal foreskin was collected following circumcision and primary dermal fibroblasts were isolated to perform adipocyte differentiation and insulin stimulation experiments. Human neonatal foreskin primary fibroblasts take up lipid when …

Effects Of Permethrin, A Pyrethroid Insecticide, On Glucose And Lipid Metabolism, Xiao Xiao

Doctoral Dissertations

Over the last few decades, the decline of using organochlorine and organophosphorus insecticides has partially contributed to the rising utilization of newer synthetic insecticides, which are considered as less harmful and more environmental friendly than the older generation of insecticides. Pyrethroid insecticides are one of the newer insecticide classes reported with better biodegradability and low mammalian toxicity without sacrificing its insecticidal efficacy. Permethrin is one of the most widely used pyrethroid insecticides with structural similarity with natural pyrethrin insecticide from the flowers of Chrysanthemum cinerariifolium. Since its introduction in the 1970’s, permethrin has been extensively used in medicine, military, …

Human Kinome In Skeletal Muscle Insulin Resistance, Yue Qi

Wayne State University Dissertations

Protein kinases play fundamental roles in regulation of biological processes and functions, such as insulin signaling and glucose metabolism. Dysregulation of protein kinases may cause impaired cell signaling and human diseases, such as metabolic syndrome and type 2 diabetes (T2D). Skeletal muscle is the main site responsible for insulin-stimulated glucose disposal, and insulin resistance in skeletal muscle is one of the key features of the pathogenesis of T2D. Therefore, malfunction of protein kinases and their interaction proteins may contribute to the molecular mechanism of insulin resistance in human skeletal muscle. However, no large scale profiling study has been reported to …

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 …

Thrombospondin1 Deficiency Attenuates Obesity-Associated Microvascular Complications In Apoe-/- Mice, Hasiyeti Maimaitiyiming, Kate Clemons, Qi Zhou, Heather Norman, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Obesity is associated with insulin resistance and the increased development of vascular complications. Previously, we have demonstrated that thrombospondin1 (TSP1) regulates macrophage function and contributes to obesity associated inflammation and insulin resistance. However, the role of TSP1 in the development of obesity associated vascular complications is not clear. Therefore, in the current study, we investigated whether TSP1 deficiency protects mice from obesity associated micro as well as macro-vascular complications in ApoE-/- mice. In this study, male ApoE-/- mice and ApoE-/-TSP1-/- mice were fed with a low-fat (LF) or a high-fat (HF) diet for 16 weeks. We found that body weight …

Cd47 Deficiency Protects Mice From Diet-Induced Obesity And Improves Whole Body Glucose Tolerance And Insulin Sensitivity, Hasiyeti Maimaitiyiming, Heather Norman, Qi Zhou, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling. Although it has been extensively studied in cancer and ischemia, CD47 function in obesity has never been explored. In this study, we utilized CD47 deficient mice in a high-fat diet induced obesity model to study for the first time whether CD47 plays a role in the development of obesity and metabolic complications. Male CD47 deficient and wild type (WT) control mice were fed with either low fat (LF) or high fat (HF) diets for 16 weeks. Interestingly, we found that CD47 deficient mice were …

Cardioprotection By Controlling Hyperamylinemia In A "Humanized" Diabetic Rat Model, Sanda Despa, Savita Sharma, Todd R. Harris, Hua Dong, Ning Li, Nipavan Chiamvimonvat, Heinrich Taegtmeyer, Kenneth B. Margulies, Bruce D. Hammock, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Chronic hypersecretion of the pancreatic hormone amylin is common in humans with obesity or prediabetic insulin resistance and induces amylin aggregation and proteotoxicity in the pancreas. We recently showed that hyperamylinemia also affects the cardiovascular system. Here, we investigated whether amylin aggregates interact directly with cardiac myocytes and whether controlling hyperamylinemia protects the heart.

METHODS AND RESULTS: By Western blot, we found abundant amylin aggregates in lysates of cardiac myocytes from obese patients, but not in controls. Aggregated amylin was elevated in failing hearts, suggesting a role in myocyte injury. Using rats overexpressing human amylin in the pancreas (HIP …

Sleep Duration And Diabetes In An Adult Population Of Rural Upstate New York, Tarak Shrestha

Legacy Theses & Dissertations (2009 - 2024)

Introduction: Within the past five decades, there has been a rapid increase in the number of diabetic cases in the US. The number of diabetic cases increased from 1.5 million in 1959 to 25.8 million in 2011. Around the same time period, the average sleep duration per night decreased from 8 hours to 6.9 hours.

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 …

The Effect Of Alpha-Cyclodextrin On Acute Blood Lipid And Glycemic Responses To A Fat Containg Meal, Evan Neil Fletcher

Wayne State University Theses

Obesity and hyperlipidemia have become major concerns in the United States over the past 30 years. Alpha-Cyclodextrin (á-CD), a naturally occurring soluble dietary fiber, has been shown to reduce dietary fat absorption and improve blood lipid levels in an animal model (mouse and rat) and in human studies. In the current double blind study, 34 healthy male and female participants were recruited to test if á-CD had any acute effect on blood lipid and glycemic responses to a fat containing meal. The participants received the á-CD on one occasion and a placebo the other to determine if there was any …

Exposure To Persistent Organic Pollutants And Metabolic Diseases, Zafar Zayirovich Aminov

Legacy Theses & Dissertations (2009 - 2024)

Background: The metabolic syndrome (MetS) is a group of diseases that tend to occur together, including diabetes, hypertension, central obesity, cardiovascular disease and hyperlipidemia. Exposure to persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) have been associated with increased risk of development of several of the components of the MetS.

Anti-Lipase Activity Of Quercus Infectoria G.Olivier Extract, Sirinan Thubthimthed., Sarunya Laovitthayanggoon, Parkpoom Siriarchavatana, Konlawit Chaithongsri, Chuleratana Banchonglikitkul

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Comparison Of Weight Reduction And Satisfaction Of Orlistat And Sibutramine, Somchai Anansiriwattana, Titinun Auamnoy, Pagorn Taweechotepatr

The Thai Journal of Pharmaceutical Sciences

The study was to compare and evaluate the efficacy and satisfaction of orlistat and sibutramine in Thai overweight females at Adisorn Fort Hospital, Saraburi Province, Thailand. Orlistat is a drug which increases the fecal fat excretion, with gastrointes...