Medicine and Health Sciences Commons^™

Calpain Inhibition Attenuates Adipose Tissue Inflammation And Fibrosis In Diet-Induced Obese Mice, Latha Muniappan, Aida Javidan, Weihua Jiang, Shayan Mohammadmoradi, Jessica J. Moorleghen, Wendy S. Katz, Anju Balakrishnan, Deborah A. Howatt, Venkateswaran Subramanian

Saha Cardiovascular Research Center Faculty Publications

Adipose tissue macrophages have been proposed as a link between obesity and insulin resistance. However, the mechanisms underlying these processes are not completely defined. Calpains are calcium-dependent neutral cysteine proteases that modulate cellular function and have been implicated in various inflammatory diseases. To define whether activated calpains influence diet-induced obesity and adipose tissue macrophage accumulation, mice that were either wild type (WT) or overexpressing calpastatin (CAST Tg), the endogenous inhibitor of calpains were fed with high (60% kcal) fat diet for 16 weeks. CAST overexpression did not influence high fat diet-induced body weight and fat mass gain throughout the study. …

Protective Role Of S-Adenosylmethionine Against Fructose-Induced Oxidative Damage In Obesity, Kameliya Zh Bratoeva, Mariya A. Radanova, Albena V. Merdzhanova, Ivan S. Donev

Journal of Mind and Medical Sciences

Introduction. It has been shown that S-adenosylmethionine (S-AMe) stimulates glutathione synthesis and increases cell resistance to the cytotoxic action of free radicals and pro-inflammatory cytokines. The aim of this study was to determine the effect of S-adenosylmethionine on the oxidative stress in adipose tissue in a model of fructose-induced obesity. Methods. The study was performed on male Wistar rats divided into 3 groups: control, fructose fed (HFD) (35%, 16 weeks), and HFD + S-AMe (20 mg/kg). We examined the changes in the ratio of retroperitoneal adipose tissue weight / body weight; levels of reduced glutathione (GSH) and malondialdehyde (MDA) in …

Whole Genome Sequence Analysis Of The Tallyho/Jng Mouse, James Denvir, Goran Boskovic, Jun Fan, Donald A. Primerano, Jacaline K. Parkman, Jung Han Kim

Jung Han Kim

Background: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes.

Results: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing …

Whole Genome Sequence Analysis Of The Tallyho/Jng Mouse, James Denvir, Goran Boskovic, Jun Fan, Donald A. Primerano, Jacaline K. Parkman, Jung Han Kim

Jun Fan

Background: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes. Results: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing …

Whole Genome Sequence Analysis Of The Tallyho/Jng Mouse, James Denvir, Goran Boskovic, Jun Fan, Donald A. Primerano, Jacaline K. Parkman, Jung Han Kim

Goran Boskovic

Background: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes. Results: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing …

Whole Genome Sequence Analysis Of The Tallyho/Jng Mouse, James Denvir, Goran Boskovic, Jun Fan, Donald A. Primerano, Jacaline K. Parkman, Jung Han Kim

Donald A. Primerano

Background: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes. Results: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing …

Whole Genome Sequence Analysis Of The Tallyho/Jng Mouse, James Denvir, Goran Boskovic, Jun Fan, Donald A. Primerano, Jacaline K. Parkman, Jung Han Kim

James Denvir

Background: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes.

Results: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing …

Randomized Vitamin D Supplementation In Vitamin D Deficient Obese Children From West Virginia, Yoram Elitsur Md, Deborah L. Preston

Yoram Elitsur

Objective: Vitamin D (Vit D) deficiency is a very common problem in obese children, but clinical guidelines for maintenance or treatment have not been published for this population. The aim was to assess the benefit of 2 months Vit D supplementation given to deficient obese children from WV. Design: Vit D deficient obese children were prospectively recruited. Exclusion criteria included <8 years, and medical conditions that may affect Vit D homeostasis. Participants were randomized into two supplement groups: 5,000IU/day (Group A) or 50,000IU/week (Group B). Serum 25(OH)D levels were measured at baseline and post-treatment. Results: Sixty obese children were screened of whom 39 (65%) were deficient (<20ng/ml). Of the 39 recruited, 26 completed the study. The mean serum 25(OH)D after 2 months treatment were significantly higher in Group B (p= 0.02), but most reached normal levels (>30ng/ml). Conclusions: Two months Vit D supplementation (5000IU/day or 50,000IU/week) was sufficient to normalize 25(OH)D levels in Vit D deficient obese West Virginian children.

Evaluation Of An Unfractioned Heparin Pharmacy Dosing Protocol For The Treatment Of Venous Thromboembolism In Nonobese, Obese, And Severely Obese Patients, Chad A. Knoderer, Lindsey M. Hosch, Emily Y. Breedlove, Lauren E. Scono

Chad A. Knoderer

Background: Despite large interpatient variability in dose response, heparin is utilized for treatment of venous thromboembolism (VTE). Current data on the optimal heparin dosing in obese patients are conflicting. Objective: The objective was to evaluate the time and dose required to achieve a therapeutic activated partial thromboplastin time (aPTT) in nonobese, obese, and severely obese patients using a pharmacist-directed heparin dosing protocol. Methods: This was a retrospective cohort study in a single-center community hospital inpatient setting. Adult patients receiving heparin for VTE treatment from July 1, 2013, to July 31, 2015, were evaluated. Patients were categorized into 3 groups: nonobese …

Obesity, Metabolic Factors And Risk Of Different Histological Types Of Lung Cancer: A Mendelian Randomization Study, Robert Carreras-Torres, Mattias Johansson, Philip C. Haycock, Kaitlin H. Wade, Caroline L. Relton, Richard M. Martin, George Davey Smith, Demetrius Albanes, Melinda C. Aldrich, Angeline Andrew, Susanne M. Arnold, Heike Bickeböller, Stig E. Bojesen, Hans Brunnström, Jonas Manjer, Irene Brüske, Neil E. Caporaso, Chu Chen, David C. Christiani, Warren Jay Christian, Jennifer A. Doherty, Eric J. Duell, John K. Field, Michael P. A. Davies, Michael W. Marcus, Gary E. Goodman, Kjell Grankvist, Aage Haugen, Yun-Chul Hong, Lambertus A. Kiemeney

Markey Cancer Center Faculty Publications

Background

Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.

Methods and findings

We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of …

Evaluation Of An Unfractioned Heparin Pharmacy Dosing Protocol For The Treatment Of Venous Thromboembolism In Nonobese, Obese, And Severely Obese Patients, Chad A. Knoderer, Lindsey M. Hosch, Emily Y. Breedlove, Lauren E. Scono

Scholarship and Professional Work – COPHS

Background: Despite large interpatient variability in dose response, heparin is utilized for treatment of venous thromboembolism (VTE). Current data on the optimal heparin dosing in obese patients are conflicting. Objective: The objective was to evaluate the time and dose required to achieve a therapeutic activated partial thromboplastin time (aPTT) in nonobese, obese, and severely obese patients using a pharmacist-directed heparin dosing protocol. Methods: This was a retrospective cohort study in a single-center community hospital inpatient setting. Adult patients receiving heparin for VTE treatment from July 1, 2013, to July 31, 2015, were evaluated. Patients were categorized into 3 groups: nonobese …

Optimal Nutrition And The Ever-Changing Dietary Landscape: A Conference Report., A Shao, A Drewnowski, D C Willcox, L Krämer, Christopher G Lausted, M Eggersdorfer, J Mathers, J D Bell, R K Randolph, R Witkamp, J C Griffiths

Articles, Abstracts, and Reports

The field of nutrition has evolved rapidly over the past century. Nutrition scientists and policy makers in the developed world have shifted the focus of their efforts from dealing with diseases of overt nutrient deficiency to a new paradigm aimed at coping with conditions of excess-calories, sedentary lifestyles and stress. Advances in nutrition science, technology and manufacturing have largely eradicated nutrient deficiency diseases, while simultaneously facing the growing challenges of obesity, non-communicable diseases and aging. Nutrition research has gone through a necessary evolution, starting with a reductionist approach, driven by an ambition to understand the mechanisms responsible for the effects …

Diabetic Cardiomyopathy: An Immunometabolic Perspective., Paras K. Mishra, Wei Ying, Shyam Sundar Nandi, Gautam K. Bandyopadhyay, Kaushik K. Patel, Sushil K. Mahata

Journal Articles: Cellular & Integrative Physiology

The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM. These early events are followed by steatosis (accumulation of lipid droplets) …

Clinical Significance Of A False Positive Glucose Challenge Test In Patients With A High Body Mass Index, A Borja, M Moretti, Nisha Lakhi

NYMC Faculty Publications

OBJECTIVE: To determine if there is an increased maternal or neonatal morbidity in overweight and obese patients with a false positive glucose challenge test (GCT). METHODS: Patients with a body mass index (BMI) >/=25.0 at registration were included in this prospective 36-month study. The study cohort consisted of patients with a false positive (FP) GCT, with two comparison cohorts: those with a (1) screen negative (SN) GCT result and (2) true positive (TP) GCT result. Risks were reported as odd ratios with 95% confidence intervals, with a P/=4000 g in the FP cohort, but this fell short of reaching statistical …

Genetic Risk For Obesity Predicts Nucleus Accumbens Size And Responsivity To Real-World Food Cues, Kristina Rapuano, Amanda Zieselman, William Kelley, James Sargent, Todd Heatherton, Diane Gilbert-Diamond

Dartmouth Scholarship

Obesity is a major public health concern that involves an interaction between genetic susceptibility and exposure to environmental cues (e.g., food marketing); however, the mechanisms that link these factors and contribute to unhealthy eating are unclear. Using a well-known obesity risk polymorphism (FTO rs9939609) in a sample of 78 children (ages 9-12 y), we observed that children at risk for obesity exhibited stronger responses to food commercials in the nucleus accumbens (NAcc) than children not at risk. Similarly, children at a higher genetic risk for obesity demonstrated larger NAcc volumes. Although a recessive model of this polymorphism best predicted body …

Provider Attitudes And Practice Patterns Of Obesity Management With Pharmacotherapy, Brittany Granara

Graduate College Dissertations and Theses

Background and Purpose: More than one-third of American adults are obese. The prevalence of extreme obesity is rapidly rising. Nine medications are currently approved for weight loss yet they remain under utilized with the focus primarily on lifestyle modifications. The study's objective was to determine current prescribing patterns and attitudes of weight loss medications in the management of obesity among primary care providers (PCPs).

Methods: PCPs were surveyed to determine practice patterns, attitudes, barriers, and facilitators for prescribing weight loss medications.

Conclusions: A total of 105 surveys were completed. 76% of all PCPs did not prescribe weight loss medications for …

Factors Regulating Features Of Metabolic Syndrome, Sonja S. Pijut

Theses and Dissertations--Pharmacy

The collective presence of central obesity, low HDL-cholesterol, and elevated triglycerides, blood pressure, and fasting blood glucose constitutes Metabolic Syndrome (MetS), a disease state that increases the risk of cardiovascular disease (CVD) and Type 2 Diabetes Mellitus (T2DM). Nonalcoholic fatty liver disease (NAFLD), present in up to 90% of obese adults, is also linked to MetS. As in CVD, disruptions in cholesterol metabolism play a contributing role in the development of T2DM and NAFLD. Genes involved in cholesterol synthesis, secretion, and catabolism are diurnally regulated in the liver and adipose. Disruptions in the sleep-wake cycle are thought to potentiate metabolic …

Associations Between Obesity And The Radiographic Phenotype In Knee Osteoarthritis, Mehmet Derya Demi̇rağ, Seçi̇l Özkan, Şemi̇nur Haznedaroğlu, Evi̇n Aras Kilinç, Fatma Nur Baran Aksakal, Sefer Aycan, Berna Goker

Turkish Journal of Medical Sciences

Background/aim: Investigation of the association between obesity and the distinction of radiographic patterns in knee osteoarthritis. Materials and methods: Seven hundred and thirty-four women underwent weight-bearing antero-posterior knee radiography. Osteophytes and joint space narrowing (JSN) were graded according to the OARSI atlas. Each subject was assigned to one of the following groups with respect to the maximum score: osteophyte-dominant, indeterminate, JSN-dominant, and radiographically normal. Results: Obese patients had a significantly more frequent osteophyte-dominant pattern compared to nonobese subjects (74.5% and 38%, respectively, P < 0.001). Logistic regression analysis demonstrated that obesity had a stronger association with an osteophytedominant pattern compared to a JSN-dominant pattern (OR and 95% CI = 7.16 (3.15-16.26) and 1.63 (0.96-2.78), respectively). Age had a very weak effect on the distinction to an osteophyte-dominant pattern and no effect on JSN dominance (OR and 95% CI = 1.1 (1.06-1.15) and 1.02 (0.99-1.05), respectively). Conclusion: There might be an association between obesity and the radiographic phenotype in patients with knee osteoarthritis. The findings suggest that the association between obesity and the osteophyte formation is stronger than that of JSN.

Multiethnic Genome-Wide Meta-Analysis Of Ectopic Fat Depots Identifies Loci Associated With Adipocyte Development And Differentiation, Audrey Y. Chu, Xuan Deng, Virginia A. Fisher, Alexander Drong, Yang Zhang, Mary F. Feitosa, Ching-Ti Liu, Olivia Weeks, Audrey C. Choh, Qing Duan, Thomas D. Dyer

School of Medicine Publications and Presentations

Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men for six ectopic fat traits in European, African, Hispanic, and Chinese ancestry populations, with and without sex stratification. In total, 7 new loci were identified in association with ectopic fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; PATXN1 and UBE2E2 …