Adropin: An Endocrine Link Between The Biological Clock And Cholesterol Homeostasis, 2018 Saint Louis University
Adropin: An Endocrine Link Between The Biological Clock And Cholesterol Homeostasis, Sarbani Ghoshal, Joseph R. Stevens, Cyrielle Billon, Clemence Girardet, Sadichha Sitaula, Arthur S. Leon, D.C. Rao, James S. Skinner, Tuomo Rankinen, Claude Bouchard, Marinelle V. Nuñez, Kimber L. Stanhope, Deborah A. Howatt, Alan Daugherty, Jinsong Zhang, Matthew Schuelke, Edward P. Weiss, Alisha R. Coffey, Brian J. Bennett, Praveen Sethupathy, Thomas P. Burris, Peter J. Havel, Andrew A. Butler
Physiology Faculty Publications
Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function.
Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models.
In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = 401). Analysis of hepatic Enho ...
C9orf72 Ggggcc Repeat-Associated Non-Aug Translation Is Upregulated By Stress Through Eif2alpha Phosphorylation, 2018 Johns Hopkins University
C9orf72 Ggggcc Repeat-Associated Non-Aug Translation Is Upregulated By Stress Through Eif2alpha Phosphorylation, Weiwei Cheng, Shaopeng Wang, Alexander A. Mestre, Chenglai Fu, Andres Makarem, Fengfan Xian, Lindsey R. Hayes, Rodrigo Lopez-Gonzalez, Kevin Drenner, Jie Jiang, Don W. Cleveland, Shuying Sun
Open Access Articles
Hexanucleotide repeat expansion in C9ORF72 is the most frequent cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we demonstrate that the repeat-associated non-AUG (RAN) translation of (GGGGCC) n -containing RNAs into poly-dipeptides can initiate in vivo without a 5'-cap. The primary RNA substrate for RAN translation of C9ORF72 sense repeats is shown to be the spliced first intron, following its excision from the initial pre-mRNA and transport to the cytoplasm. Cap-independent RAN translation is shown to be upregulated by various stress stimuli through phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF2alpha), the core ...
Impact Of Bodyweight On Tissue-Specific Folate Status, Genome Wide And Gene-Specific Dna Methylation In Normal Breast Tissues From Premenopausal Women, 2018 University of Massachusetts Amherst
Impact Of Bodyweight On Tissue-Specific Folate Status, Genome Wide And Gene-Specific Dna Methylation In Normal Breast Tissues From Premenopausal Women, Armina-Lyn Frederick
Obesity has reached an epidemic level in the United States. A number of epidemiological studies have established obesity as a critical risk factor for postmenopausal breast cancer (post-BC), whereas a reverse association holds prior to menopause. A significant scientific gap exists in understanding the mechanism(s) underpinning this epidemiological phenomenon, particularly the reverse association between obesity and premenopausal breast cancer (pre-BC). This study aimed to understand how folate metabolism and DNA methylation informs the association between obesity and pre-BC. Fifty normal breast tissue samples were collected from premenopausal women who underwent reduction mammoplasty. We developed and measured the breast tissue ...
Thermophilic Adaptation In Prokaryotes Is Constrained By Metabolic Costs Of Proteostasis, 2018 University of Massachusetts Medical School
Thermophilic Adaptation In Prokaryotes Is Constrained By Metabolic Costs Of Proteostasis, Sergey V. Venev, Konstantin B. Zeldovich
Open Access Articles
Prokaryotes evolved to thrive in an extremely diverse set of habitats, and their proteomes bear signatures of environmental conditions. Although correlations between amino acid usage and environmental temperature are well-documented, understanding of the mechanisms of thermal adaptation remains incomplete. Here, we couple the energetic costs of protein folding and protein homeostasis to build a microscopic model explaining both the overall amino acid composition and its temperature trends. Low biosynthesis costs lead to low diversity of physical interactions between amino acid residues, which in turn makes proteins less stable and drives up chaperone activity to maintain appropriate levels of folded, functional ...
The Prebiotic Inulin Beneficially Modulates The Gut-Brain Axis By Enhancing Metabolism In An Apoe4 Mouse Model, 2018 University of Kentucky
The Prebiotic Inulin Beneficially Modulates The Gut-Brain Axis By Enhancing Metabolism In An Apoe4 Mouse Model, Jared D. Hoffman
Theses and Dissertations--Pharmacology and Nutritional Sciences
Alzheimer’s disease (AD) is the most common form of dementia and a growing disease burden that has seen pharmacological interventions primarily fail. Instead, it has been suggested that preventative measures such as a healthy diet may be the best way in preventing AD. Prebiotics are one such potential measure and are fermented into metabolites by the gut microbiota and acting as gut-brain axis components, beneficially impact the brain. However, the impact of prebiotics in AD prevention is unknown. Here we show that the prebiotic inulin increased multiple gut-brain axis components such as scyllo-inositol and short chain fatty acids in ...
Foki Vitamin D Receptor Gene Polymorphisms And Metabolic Health In Pregnant Saudi Women, 2018 University of Massachusetts Amherst
Foki Vitamin D Receptor Gene Polymorphisms And Metabolic Health In Pregnant Saudi Women, Maysa Alzaim
Lifestyles have been dynamically changing in the past few years in Saudi Arabia, and the prevalence of non-communicable diseases (NCDs), such as obesity, diabetes, hypertension, high cholesterol, and other cardiovascular diseases (CVD), is notably increasing. In fact, NCDs are affecting a growing number of people in SA, especially women of childbearing age. Vitamin D deficiency has also become pandemic and a major public health concern among the Saudi population despite the abundance of sunlight. The most vulnerable groups are pregnant women and their newborns. Previous studies have correlated low vitamin D status with a higher risk of adverse short- and ...
High Dietary Fat And Sucrose Results In An Extensive And Time-Dependent Deterioration In Health Of Multiple Physiological Systems In Mice [Accepted Manuscript], James G. Burchfield, Melkam A. Kebede, Christopher C. Meoli, Jacqueline Stockli, P. Tess Whitworth, Amanda L. Wright, Nolan John Hoffman, Annabel Y. Minard, Xiuquan Ma, James R. Krycer, Marin E. Nelson, Shi-Xlong Tan, Belinda Yau, Kristen C. Thomas, Natalie K.Y. Wee, Ee-Cheng Khor, Ronaldo F. Enriquez, Bryce Vissel, Trevor J. Biden, Paul A. Baldock, Kyle L. Hoehn, James Cantley, Gregory J. Cooney, David E. James, Daniel J. Fazakerley
Faculty of Health Sciences Publications
Obesity is associated with metabolic dysfunction, including insulin resistance and hyperinsulinemia, and with disorders such as cardiovascular disease, osteoporosis, and neurodegen-eration. Typically, these pathologies are examined in discrete model systems and with limited temporal resolution, and whether these disorders co-occur is therefore unclear. To address this question, here we examined multiple physiological systems in male C57BL/6J mice following prolonged exposure to a high-fat/high-sucrose diet (HFHSD). HFHSD-fed mice rapidly exhibited metabolic alterations, including obesity, hyperleptinemia, physical inactivity, glucose intolerance, peripheral insulin resistance, fasting hyperglycemia, ectopic lipid deposition, and bone deterioration. Prolonged exposure to HFHSD resulted in morbid obesity, ectopic ...
Arginine Does Not Rescue P.Q188r Mutation Deleterious Effect In Classic Galactosemia, 2018 Australian Catholic University
Arginine Does Not Rescue P.Q188r Mutation Deleterious Effect In Classic Galactosemia, Minela Haskovic, Britt Derks, Liesbeth Van Der Ploeg, Jorn Trommelen, Jean Nyakayiru, Luc J. C. Van Loon, Sabrina Mackinnon, Wyatt W. Yue, Roy W. A. Peake, Li Zha, Didem Demirbas, Wanshu Qi, Xiaoping Huang, Gerard T. Berry, Jelle Achten, Jörgen Bierau, M. Estela Rubio-Gozalbo, Ana I. Coelho
Faculty of Health Sciences Publications
Background: Classic galactosemia is a rare genetic metabolic disease with an unmet treatment need. Current standard of care fails to prevent chronically-debilitating brain and gonadal complications. Many mutations in the GALT gene responsible for classic galactosemia have been described to give rise to variants with conformational abnormalities. This pathogenic mechanism is highly amenable to a therapeutic strategy based on chemical/pharmacological chaperones. Arginine, a chemical chaperone, has shown beneficial effect in other inherited metabolic disorders, as well as in a prokaryotic model of classic galactosemia. The p.Q188R mutation presents a high prevalence in the Caucasian population, making it a ...
No Evidence Of Direct Association Between Glut4 And Glycogen In Human Skeletal Muscle, 2018 Australian Catholic University
No Evidence Of Direct Association Between Glut4 And Glycogen In Human Skeletal Muscle, Robyn M. Murphy, Marcelo Flores-Opazo, Barnaby P. Frankish, Andrew Garnham, David Stapleton, Mark Hargreaves
Faculty of Health Sciences Publications
Previous studies have demonstrated that exercise increases whole body and skeletal muscle insulin sensitivity that is linked with increased GLUT4 at the plasma membrane following insulin stimulation and associated with muscle glycogen depletion. To assess the potential direct association between muscle glycogen and GLUT4, seven untrained, male subjects exercised for 60 min at ~75% VO2 peak, with muscle samples obtained by percutaneous needle biopsy immediately before and after exercise. Exercise reduced muscle glycogen content by ~43%. An ultracentrifugation protocol resulted in a ~2‐3‐fold enriched glycogen fraction from muscle samples for analysis. Total GLUT4 content was unaltered by exercise ...
Marijuana And The Teenage Brain: Public Health Impact, 2018 University of Vermont
Marijuana And The Teenage Brain: Public Health Impact, Katie C. Warther
Family Medicine Clerkship Student Projects
This project explores the neurobiological impact of teenage marijuana use, and the ways that public health interventions can help educate adolescents and delay the onset of use.
The Effects Of Intensified Training On Resting Metabolic Rate (Rmr), Body Composition And Performance In Trained Cyclists, 2018 Australian Catholic University
The Effects Of Intensified Training On Resting Metabolic Rate (Rmr), Body Composition And Performance In Trained Cyclists, Amy L. Woods, Anthony J. Rice, Laura A. Garvican-Lewis, Alice M. Wallett, Bronwen Lundy, Margot A. Rogers, Marijke Welvaert, Shona Halson, Andrew Mckune, Kevin G. Thompson
Faculty of Health Sciences Publications
Background: Recent research has demonstrated decreases in resting metabolic rate (RMR), body composition and performance following a period of intensified training in elite athletes, however the underlying mechanisms of change remain unclear. Therefore, the aim of the present study was to investigate how an intensified training period, designed to elicit overreaching, affects RMR, body composition, and performance in trained endurance athletes, and to elucidate underlying mechanisms. Method: Thirteen (n = 13) trained male cyclists completed a six-week training program consisting of a “Baseline” week (100% of regular training load), a “Build” week (~120% of Baseline load), two “Loading” weeks (~140, 150 ...
Body Composition Vs Athletic Performance In Volleyball, 2018 The University of Akron
Body Composition Vs Athletic Performance In Volleyball, Elizabeth Decaro
Williams Honors College, Honors Research Projects
Objectives: The goal of this study was to determine if body composition affected athletic performance in the sport of volleyball at the University of Akron.
Methods: The study was conducted in the School of Sports Science & Wellness Education on the 3rd floor of Infocision Stadium at the University of Akron using the computer containing the Bod Pod data for the women’s volleyball team.
Results: 20 subjects of the women’s varsity volleyball team were studied. The averages of each test were varied between the different skills tests in counter-movement vertical jump, approach vertical jump, block, broad jump, chin-ups ...
Early Diagnosis And Nutritional Treatment Stabilizes Neuropsychiatric Disorders, 2018 Edith Cowan University
Early Diagnosis And Nutritional Treatment Stabilizes Neuropsychiatric Disorders, Ian James Martins
ECU Publications Post 2013
The reliable diagnostic identification of neuropsychiatric disorders such as schizophrenia, bipolar disease, and depression has been associated with some biological markers (genomics, proteomics, metabolomics) but to date, these markers do not have the sensitivity/specificity of a diagnostic test. Biomarker tests that are relevant to global chronic disease are now applicable to neuropsychiatric diseases to prevent autoimmune disease, endoplasmic reticulum stress associated mitophagy with relevance to neuron apoptosis. Metabolic abnormalities has been linked to neuropsychiatric disorder with the careful nutritional assessment of patients reported in many published studies. Early interventions with genomic medicine now assist in the prevention of autoimmune ...
Metabolic Dysregulation And Cancer Mortality In A National Cohort Of Blacks And Whites, 2017 University of Kentucky
Metabolic Dysregulation And Cancer Mortality In A National Cohort Of Blacks And Whites, Tomi Akinyemiju, Justin Xavier Moore, Suzanne Judd, Susan Lakoski, Michael Goodman, Monika M. Safford, Maria Pisu
Epidemiology Faculty Publications
Background: We examined the association between metabolic dysregulation and cancer mortality in a prospective cohort of Black and White adults.
Methods: A total of 25,038 Black and White adults were included in the analysis. Metabolic dysregulation was defined in two ways: 1) using the joint harmonized criteria for metabolic syndrome (MetS) and 2) based on factor analysis of 15 variables characterizing metabolic dysregulation. We estimated hazards ratios (HRs) and 95% confidence intervals (CIs) for the association of MetS and metabolic dysregulation with cancer mortality during follow-up using Cox proportional hazards models.
Results: About 46% of Black and 39% of ...
Nmd Monitors Translational Fidelity 24/7, 2017 University of Massachusetts Medical School
Nmd Monitors Translational Fidelity 24/7, Alper Celik, Feng He, Allan Jacobson
Open Access Articles
Nonsense-mediated mRNA decay (NMD) is generally thought to be a eukaryotic mRNA surveillance pathway tasked with the elimination of transcripts harboring an in-frame premature termination codon (PTC). As presently conceived, NMD acting in this manner minimizes the likelihood that potentially toxic polypeptide fragments would accumulate in the cytoplasm. This notion is to be contrasted to the results of systematic RNA-Seq and microarray analyses of NMD substrates in multiple model systems, two different experimental approaches which have shown that many mRNAs identified as NMD substrates fail to contain a PTC. Our recent results provide insight into, as well as a possible ...
Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel
Biochemistry -- Faculty Publications
Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood.
Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo.
Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation ...
Defining Electron Bifurcation In The Electron-Transferring Flavoprotein Family, 2017 Montana State University
Defining Electron Bifurcation In The Electron-Transferring Flavoprotein Family, Amaya M. Garcia Costas, Saroj Poudel, Anne-Frances Miller, Gerrit J. Schut, Rhesa N. Ledbetter, Kathryn R. Fixen, Lance C. Seefeldt, Michael W. W. Adams, Caroline S. Harwood, Eric S. Boyd, John W. Peters
Chemistry Faculty Publications
Electron bifurcation is the coupling of exergonic and endergonic redox reactions to simultaneously generate (or utilize) low- and high-potential electrons. It is the third recognized form of energy conservation in biology and was recently described for select electron-transferring flavoproteins (Etfs). Etfs are flavin-containing heterodimers best known for donating electrons derived from fatty acid and amino acid oxidation to an electron transfer respiratory chain via Etf-quinone oxidoreductase. Canonical examples contain a flavin adenine dinucleotide (FAD) that is involved in electron transfer, as well as a non-redox-active AMP. However, Etfs demonstrated to bifurcate electrons contain a second FAD in place of the ...
Inhibition Of Cholesterol Biosynthesis Through Rnf145-Dependent Ubiquitination Of Scap, 2017 University of California - Los Angeles
Inhibition Of Cholesterol Biosynthesis Through Rnf145-Dependent Ubiquitination Of Scap, Li Zhang, Prashant Rajbhandari, Christina Priest, Jaspreet Sandhu, Xiaohui Wu, Ryan E. Temel, Antonio Castrillo, Thomas Q. De Aguiar Vallim, Tamer Sallam, Peter Tontonoz
Saha Cardiovascular Research Center Faculty Publications
Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma. Mechanistic studies show ...
Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, 2017 University of Kentucky
Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, Jared D. Hoffman, Ishita Parikh, Stefan J. Green, George Chlipala, Robert P. Mohney, Mignon Keaton, Bjoern Bauer, Anika M. S. Hartz, Ai-Ling Lin
Sanders-Brown Center on Aging Faculty Publications
Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes ...
A Cross-Sectional Study Of Dietary And Genetic Predictors Of Blood Folate Levels In Healthy Young Adults, Daniel Cummings, Kevin F. Dowling, Noah J. Silverstein, Alexandra S. Tanner, Hamdi Eryilmaz, Jordan W. Smoller, Joshua L. Roffman
Open Access Articles
Since 1998, the U.S. has mandated folic acid (FA) fortification of certain grain products to reduce the risk of neural tube defects. Folate intake and red blood cell (RBC) folate concentrations increased substantially post-intervention, although recent studies raise concerns about the level of ongoing benefit. This study investigated blood folate level determinants in healthy young adults, including intake of naturally occurring food folate, synthetic FA, and the interaction of naturally occurring food folate with a common missense variant in the FOLH1 gene thought to affect absorption. Participants (n = 265) completed the Diet History Questionnaire II, RBC folate testing, and ...