DOCSLIB.ORG

Tamiasciurus Hudsonicus)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Tamiasciurus Hudsonicus) THERMAL ADAPTATION IN THE AMERICAN RED SQUIRREL (TAMIASCIURUS HUDSONICUS) A Dissertation Presented to the Faculty of the Graduate School of Cornell University In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy by Fríða Jóhannesdóttir January 2017 © 2017 Fríða Jóhannesdóttir THERMAL ADAPTATION IN THE AMERICAN RED SQUIRREL (TAMIASCIURUS HUDSONICUS) Fríða Jóhannesdóttir, Ph.D. Cornell University 2017 Temperature is one of the most important environmental variables impacting organisms. For endotherms, temperature can be extremely testing since they need to maintain a constant core body temperature at any given ambient temperature. However, endotherms can survive both in very hot areas and very cold areas and mammals are, for example, found throughout the world and widespread species may face temperature differences of more than 80C over their distribution range. Recent changes in climate are likely to have great impact on thermoregulatory abilities and with increased regional temperatures due to anthropogenic climate change more and more species are being pushed to, or beyond their thermal limits in parts of their distribution, making an understanding of adaptation to temperature particularly important. The following series of studies examine multiple aspects of thermal adaptation in the American red squirrel (Tamiasciurus hudsonicus). The first chapter asks if the distribution of the species is limited by temperature. Indeed, three of the major predictors of the species distribution reflect temperature, i.e. mean annual temperature, minimum temperature of the coldest month and maximum temperature of the warmest month. Knowing the importance of climate in determining the species niche helps us understand the selective pressures it asserts. The second and third chapters discuss adaptations found in the morphology of T.hudsonicus that relate to temperature. Both whole body and skull dimensions vary with temperature, with smaller animals being found in colder areas, either as a response to reduction of heat loss in cold conditions or i increased heat loss in hot conditions. This is consistent with Bergmann’s Rule, but with regards Allen’s Rule, only one protuberance or appendage – the nose - was found to show an adaptive trend and that shows a relationship with humidity rather than temperature. The fourth chapter examines variation in gene expression levels in response to temperature and elevation. The gene expression responses suggest that T.hudsonicus has a decreased metabolic activity in cold conditions compared to warm (or alternatively increased metabolic activity in warm conditions) and shows greater metabolic responses to increased elevation than to temperature. Overall T.hudsonicus is found to live within limits determined by temperature and shows both morphological and gene expression response to temperature. ii BIOGRAPHICAL SKETCH Fríða Jóhannesdóttir was born in Iceland late July during Iceland’s one week of summer. She lived close to the Arctic Circle in Akureyri until moving to the capital city, Reykjavík, to study Biology at the University of Iceland. This decision was made based on her interest in genetics following the cloning of Dolly the sheep and the founding of DeCode. Thankfully Professor Páll Hersteinsson showed her the light and turned her in the direction of mammal ecology prompting her to move to Scotland to finish her BSc degree at the University of Aberdeen. Following her time in Scotland Fríða took a year off from science and worked with children with special needs before deciding that the University system might have more need for her skill than the pre- schools. She therefore moved again to the UK to complete a Masters in Ecology and Environmental Management at the University of York. It was during that time she learnt that not all genetic studies have to involve Drosophila but can focus on crucial issues such as looking at the evolutionary ecology of small mammals. With that in mind she joined the lab of Jeremy Searle which led her to Cornell to do a PhD with him there. At Cornell Fríða was determined to understand how a widespread mammal can deal with a wide temperature range, a question close to her heart due to her inability to thermoregulate. After a false start on a European species she sat down with a mammal guide looking for a species that would have appropriate distribution and ecology to answer the question and chose the cutest one, the American red squirrel. Fríða thesis work took her to the corners of the species distribution, allowing her to visit 36 states in the US and 8 provinces of Canada during her stay in North America. iii This thesis is dedicated to Yorkshire tea. Without it, all of this would never have happened. May it continue supporting me through science for a long time to come. iv ACKNOWLEDGEMENTS I would like to specially thank my advisor Jeremy B. Searle for his unwavering support and patience over the years. I would also like to thank my committee, Kelly Zamudio, the late Rick Harrison and Monica Geber for picking up where Rick sadly left off. I would like to thank Jacob Höglund and Paulo Celio Alves for supporting me during my time in their respective labs in Sweden and Portugal in my last year. Various members of the Searle lab have been instrumental in this work, especially Jacob Tyrell who supported me during four field seasons and collected around half of all the field samples. My undergraduate students Brian Magnier, Brian O’Toole, Cassandra Ramirez and Camille Mangiaratti all impressed me with their hard work and determination in and out of the field and all contributed beyond words to this thesis. Additionally, Margherita Collini, Beatriz Oliva, Nick Fletcher, Rodrigo Vega and Michelle Alexander provided invaluable help in the field. Finally, Tom White and Heidi Eager provided both intellectual and emotional support that can never be repaid. I would have been unable to complete this work without help from a large number of people both at museums and field location. I am first of all grateful to Charles Dardia (Cornell University Museum of Vertebrates) who has been immensely supportive throughout my time in Ithaca helping with specimen preparation, and helping me and my field assistants get certification for collecting. Charles was also supportive during my time as a lab instructor for the Mammalogy course. Additionally, Eileen Westwig (American Museum of Natural History), William Stanley and Rebecca Banasiak (Field Museum of Natural History) and Suzanne Peurach (National Museum of Natural History) provided invaluable assistance while obtaining museum v data. I would also like to thank Burton Lim & Jacqueline Miller (Royal Ontario Museum), Nikole Castleberry (Georgia Museum of Natural History), Samantha Delserra (Bell Museum), Suzanne McLaren (Carnegie Museum of Natural History), Ray Poulin (Royal Saskatchewan Museum), Cindy Opitz (Univeresity of Iowa Museum of Natural History), Kamal Khidas (Canadian Museum of Nature), Virginie Millien & Anthony Wayne Howell (Redpath Museum), Timothy Gaudin (University of Tennessee at Chattanooga Museum), Donald McAlpine (New Brunswick Museum) & Duke Rogers (Monte L. Bean Life Science Museum) for specimen data. I am thankful for the help of Frank Maus, Rob Hoelscher, Jon Morton, Jeff Gross, Jeff Wells and many, many others including private land owners and National Forest staff in various states for help with finding field sites and allowing me to work there. Many thanks to Jeff Glaubitz, Qi Sun and Minghui Wang for help with bioinformatics and Erika Mudrak for help with statistics. I am additionally extremely grateful to Andrew McAdam for introducing me to the red squirrel and showing me the ropes and to Helga Óskarsdóttir for spending a part of her US holiday helping me collect data at the National Museum of Natural History. Financial support for this work came from various sources. Stipend support came from the Andrew and Margaret Paul Fellowship in the Life Sciences, Olin Graduate Fellowship and through teaching. Research support came from the Heredity Fieldwork grant (Genetics Society), the Lewis and Clark Fund for Exploration and Field Research, the Betty Miller ’47 Francis Fund, the Sigma Xi Grants in Aid of Research, the Theodore Roosevelt Memorial Fund, the Kieckhefer Adirondack Fellowship, the Department of Ecology and Evolutionary Biology Graduate Student Research Fund, the Cornell Graduate School Research Travel Grant, and the Cornell Sigma Xi Research Grant. vi I would like to thank my family in Iceland and friends, who became a family away from home in Ithaca. I would especially like to thank Amos, Denise, Nancy, Indrani, Monica, Gui, Ana, Alberto and David for many happy memories and for listening to rants and providing a support during hard times. Finally, I would like to thank the American red squirrels, a living proof that something small, common and seemingly insignificant can be the source of wonder, amazement and enthusiasm beyond words. Who needs megafauna when we have small mammals! vii TABLE OF CONTENTS BIOGRAPHICAL SKETCH iii DEDICATION iv ACKNOWLEDGEMENTS v TABLE OF CONTENTS viii LIST OF FIGURES ix LIST OF TABLES x CHAPTER 1 The thermal niche of the American red squirrel (Tamiasciurus hudsonicus) 1 CHAPTER 2 Adaptive geographic variation in external morphology in the American red squirrel, Tamiasciurus hudsonicus 18 SUPPLEMENTARY MATERIAL 2 45 CHAPTER 3 Range-wide variation in skull morphometry in the American red squirrel, Tamiasciurus hudsonicus 63 SUPPLEMENTARY MATERIAL 3 88 CHAPTER 4 Gene expression responses of the American red squirrel (Tamiasciurus hudsonicus) to temperature and elevation 106 SUPPLEMENTARY MATERIAL 4 130 viii LIST OF FIGURES Figure 1.1 Locations of specimens used in the study 6 Figure 1.2 Climatic species distribution model of T.hudsonicus for North America 9 Figure 1.3 Full species distribution model of T.hudsonicus for North America 9 Figure 1.4 Importance of each variable for the full species distribution model 10 Figure 1.5 Response curves of the best supported climatic predictors 10 Figure 2.1 Collection locations for all specimens analyzed in the chapter 25 Figure 2.2 Criteria used to classify T.hudsonicus specimens into age classes.
Load more

Recommended publications
  • The Interplay Between Angiopoietin-Like Proteins and Adipose Tissue: Another Piece of the Relationship Between Adiposopathy and Cardiometabolic Diseases?
    International Journal of Molecular Sciences Review The Interplay between Angiopoietin-Like Proteins and Adipose Tissue: Another Piece of the Relationship between Adiposopathy and Cardiometabolic Diseases? Simone Bini *,† , Laura D’Erasmo *,†, Alessia Di Costanzo, Ilenia Minicocci , Valeria Pecce and Marcello Arca Department of Translational and Precision Medicine, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy; [email protected] (A.D.C.); [email protected] (I.M.); [email protected] (V.P.); [email protected] (M.A.) * Correspondence: [email protected] (S.B.); [email protected] (L.D.) † These authors contributed equally to this work. Abstract: Angiopoietin-like proteins, namely ANGPTL3-4-8, are known as regulators of lipid metabolism. However, recent evidence points towards their involvement in the regulation of adipose tissue function. Alteration of adipose tissue functions (also called adiposopathy) is considered the main inducer of metabolic syndrome (MS) and its related complications. In this review, we intended to analyze available evidence derived from experimental and human investigations highlighting the contribution of ANGPTLs in the regulation of adipocyte metabolism, as well as their potential role in common cardiometabolic alterations associated with adiposopathy. We finally propose a model of ANGPTLs-based adipose tissue dysfunction, possibly linking abnormalities in the angiopoietins to the induction of adiposopathy and its related disorders. Keywords: adipose tissue; adiposopathy; brown adipose tissue; ANGPTL3; ANGPTL4; ANGPTL8 Citation: Bini, S.; D’Erasmo, L.; Di Costanzo, A.; Minicocci, I.; Pecce, V.; Arca, M. The Interplay between 1. Introduction Angiopoietin-Like Proteins and Adipose tissue (AT) is an important metabolic organ and accounts for up to 25% of Adipose Tissue: Another Piece of the healthy individuals’ weight.
    [Show full text]
  • Regulation of Angiopoietin-Like Protein 8 Expression Under Different Nutritional and Metabolic Status
    2019, 66 (12), 1039-1046 Review Regulation of angiopoietin-like protein 8 expression under different nutritional and metabolic status Chang Guo1), Zhicong Zhao1), Xia Deng1), Zian Chen2), Zhigang Tu2) and Guoyue Yuan1) 1) Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China 2) Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, China Abstract. Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with increasing prevalence worldwide. Angiopoietin-like protein 8 (ANGPTL8), a member of the angiopoietin-like protein family, is involved in glucose metabolism, lipid metabolism, and energy homeostasis and believed to be associated with T2DM. Expression levels of ANGPTL8 are often significantly altered in metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD) and diabetes mellitus. Studies have shown that ANGPTL8, together with other members of this protein family, such as angiopoietin-like protein 3 (ANGPTL3) and angiopoietin-like protein 4 (ANGPTL4), regulates the activity of lipoprotein lipase (LPL), thereby participating in the regulation of triglyceride related lipoproteins (TRLs). In addition, members of the angiopoietin-like protein family are varyingly expressed among different tissues and respond differently under diverse nutritional and metabolic status. These findings may provide new options for the diagnosis and treatment of diabetes, metabolic syndromes and other diseases. In this review, the interaction between ANGPTL8 and ANGPTL3 or ANGPTL4, and the differential expression of ANGPTL8 responding to different nutritional and metabolic status during the regulation of LPL activity were reviewed. Key words: Angiopoietin-like protein 8 (ANGPTL8), Diabetes mellitus, Metabolic status, Nutritional status Introduction under capillary endothelial cells [6]. LPL has hydrolytic activity in the form of dimer, and the dissociation of LPL Triglycerides (TGs) are one of the most important sub‐ dimer is the key to its spontaneous inactivation [7].
    [Show full text]
  • The Metabolic Effects of Angiopoietin-Like Protein 8 (ANGPLT8) Are Differentially Regulated By
    bioRxiv preprint doi: https://doi.org/10.1101/734954; this version posted August 15, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The Metabolic Effects of Angiopoietin-like protein 8 (ANGPLT8) are Differentially Regulated by Insulin and Glucose in Adipose Tissue and Liver and are Controlled by AMPK Signaling Lu Zhang1, Chris E. Shannon1, Terry M. Bakewell1, Muhammad A. Abdul-Ghani1, Marcel Fourcaudot1, and Luke Norton1* Affiliations: 1Diabetes Division, University of Texas Health Science Center, San Antonio, TX Key words: ANGPTL8, Insulin, Lipid, Adipose Tissue, Liver, Transcription factor Running title: Regulation and function of ANGPTL8 Word Count (main): 3,493 Word Count (abstract): 249 Figures and Tables: 6 Figures, 3 Tables, 4 Supplementary Figures *Address all correspondence to: Luke Norton, PhD Email: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/734954; this version posted August 15, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract Objective: The angiopoietin-like protein (ANGPTL) family represents a promising therapeutic target for dyslipidemia, which is a feature of obesity and type 2 diabetes (T2DM). The aim of the present study was to determine the metabolic role of ANGPTL8 and to investigate its nutritional, hormonal and molecular regulation in key metabolic tissues.
    [Show full text]
  • Identification of the Active Constituents and Significant Pathways of Cangfu Daotan Decoction for the Treatment of PCOS Based on Network Pharmacology
    Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2020, Article ID 4086864, 15 pages https://doi.org/10.1155/2020/4086864 Research Article Identification of the Active Constituents and Significant Pathways of Cangfu Daotan Decoction for the Treatment of PCOS Based on Network Pharmacology Wenting Xu , Mengyu Tang , Jiahui Wang , and Lihong Wang Department of Reproduction, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Suzhou, Jiangsu, China Correspondence should be addressed to Lihong Wang; [email protected] Received 18 December 2019; Accepted 27 January 2020; Published 22 February 2020 Academic Editor: Deborah A. Kennedy Copyright © 2020 Wenting Xu et al. ,is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Polycystic ovary syndrome (PCOS) is the most common female endocrine disease. Cangfu Daotan Decoction (CDD) can effectively relieve the clinical symptoms of PCOS patients. Methods. To explore the active ingredients and related pathways of CDD for treating PCOS, a network pharmacology-based analysis was carried out. ,e active ingredients of CDD and their potential targets were obtained from the TCM system pharmacology analysis platform. ,e obtained PCOS-related genes from OMIM and GeneCards were imported to establish protein-protein interaction networks in STRING. Finally, GO analysis and significant pathway analysis were conducted with the RStudio (Bioconductor) database. Results. A total of 111 active compounds were obtained from 1433 ingredients present in the CDD, related to 118 protein targets. In addition, 736 genes were found to be closely related to PCOS, of which 44 overlapped with CDD and were thus considered therapeutically relevant.
    [Show full text]
  • Aspects Genotypiques Et Phenotypiques Des Dyslipidemies
    N° 244 - 2014 Année 2014 THESE UNIVERSITE LYON 1 – UNIVERSITE CLAUDE BERNARD Ecole Doctorale Interdisciplinaire Sciences-Santé Diplôme de Doctorat Spécialité Biochimie par Mathilde Charcosset Di Filippo Aspects génotypiques et phénotypiques des dyslipidémies primitives rares affectant le métabolisme des lipoprotéines riches en triglycérides Soutenue le 20 novembre 2014 Directeur de Thèse : Professeur Philippe MOULIN Co-encadrant : Docteur Agnès SASSOLAS JURY Monsieur le Professeur Philippe MOULIN Directeur de thèse Madame le Professeur Laurence DUVILLARD Rapporteur Monsieur le Professeur Jean Marc LACORTE Rapporteur Monsieur le Docteur Philippe LESNIK Examinateur Monsieur le Professeur René VALERO Examinateur Monsieur le Docteur Hubert VIDAL Examinateur UNIVERSITE CLAUDE BERNARD - LYON 1 Président de l’Université M. François-Noël GILLY Vice-président du Conseil d’Administration M. le Professeur Hamda BEN HADID Vice-président du Conseil des Etudes et de la Vie Universitaire M. le Professeur Philippe LALLE Vice-président du Conseil Scientifique M. le Professeur Germain GILLET Directeur Général des Services M. Alain HELLEU COMPOSANTES SANTE Faculté de Médecine Lyon Est – Claude Bernard Directeur : M. le Professeur J. ETIENNE Faculté de Médecine et de Maïeutique Lyon Sud – Charles Mérieux Directeur : Mme la Professeure C. BURILLON Faculté d’Odontologie Directeur : M. le Professeur D. BOURGEOIS Institut des Sciences Pharmaceutiques et Biologiques Directeur : Mme la Professeure C. VINCIGUERRA Institut des Sciences et Techniques de la Réadaptation Directeur : M. le Professeur Y. MATILLON Département de formation et Centre de Recherche en Biologie Directeur : Mme. la Professeure A-M. SCHOTT Humaine COMPOSANTES ET DEPARTEMENTS DE SCIENCES ET TECHNOLOGIE Faculté des Sciences et Technologies Directeur : M. F. DE MARCHI Département Biologie Directeur : M.
    [Show full text]
  • Elevated Levels of Betatrophin in Patients with Newly Diagnosed Diabetes
    ORIGINAL ARTICLE ISSN 2450–7458 Rafał Maciulewski1, Anna Zielińska-Maciulewska1, Katarzyna Siewko1, Gabryela Kozłowska1, Danuta Lipińska1, Anna J. Milewska2, Maria Górska1, Adam Krętowski1, Małgorzata Szelachowska1 1Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Poland 2Department of Statistics and Medical Informatics, Medical University of Bialystok, Poland Elevated levels of betatrophin in patients with newly diagnosed diabetes ABSTRACT betatrophin, triglyceride (TG) and high-density lipopro- Introduction. Betatrophin is primarily produced in the tein (HDL) levels in all study participants, and C-peptide liver and regulates the metabolism of triglycerides. in the T1DM group. Its elevated concentration might be associated with Conclusions. Betatrophin concentration was signi- an increased risk of type 2 diabetes. The aim of the ficantly elevated in patients with newly diagnosed study was to evaluate the impact of betatrophin on T1DM and T2DM, compared to the control group and beta cell function and to compare the concentration of could be a biomarker of diabetes. Our study provided betatrophin in patients newly diagnosed with type 1 evidence which supports the impact of betatrophin diabetes mellitus (T1DM including LADA), type 2 on lipid metabolism. The positive correlation between diabetes mellitus (T2DM) and a control group (CG) of betatrophin and C-peptide in the T1DM group suggests healthy volunteers. that betatrophin is associated with insulin secretion in Patients and methods. The study included 210 patients T1DM. (Clin Diabetol 2019; 8, 2: 110–115) with newly diagnosed diabetes (70 with T1DM, 140 with T2DM) and 70 CG. To evaluate the relationship Key words: betatrophin, C-peptide, glucagon between betatrophin and insulin secretion, a glucagon stimulation test, newly diagnosed diabetes stimulation test was conducted.
    [Show full text]
  • Investigating the Effect of Chronic Activation of AMP-Activated Protein
    Investigating the effect of chronic activation of AMP-activated protein kinase in vivo Alice Pollard CASE Studentship Award A thesis submitted to Imperial College London for the degree of Doctor of Philosophy September 2017 Cellular Stress Group Medical Research Council London Institute of Medical Sciences Imperial College London 1 Declaration I declare that the work presented in this thesis is my own, and that where information has been derived from the published or unpublished work of others it has been acknowledged in the text and in the list of references. This work has not been submitted to any other university or institute of tertiary education in any form. Alice Pollard The copyright of this thesis rests with the author and is made available under a Creative Commons Attribution Non-Commercial No Derivatives license. Researchers are free to copy, distribute or transmit the thesis on the condition that they attribute it, that they do not use it for commercial purposes and that they do not alter, transform or build upon it. For any reuse or redistribution, researchers must make clear to others the license terms of this work. 2 Abstract The prevalence of obesity and associated diseases has increased significantly in the last decade, and is now a major public health concern. It is a significant risk factor for many diseases, including cardiovascular disease (CVD) and type 2 diabetes. Characterised by excess lipid accumulation in the white adipose tissue, which drives many associated pathologies, obesity is caused by chronic, whole-organism energy imbalance; when caloric intake exceeds energy expenditure. Whilst lifestyle changes remain the most effective treatment for obesity and the associated metabolic syndrome, incidence continues to rise, particularly amongst children, placing significant strain on healthcare systems, as well as financial burden.
    [Show full text]
  • A Short Review on ANGPTL-8 As an Important Regulator in Diabetes
    Avicenna Journal of Medical Biochemistry doi:10.34172/ajmb.2019.11 2019 December;7(2):61-63 http://ajmb.umsha.ac.ir Review Article A Short Review on ANGPTL-8 as an Important Regulator in Diabetes Maryam Esfahani1, Mohamad Taghi Goodarzi2* 1Ph.D. in Clinical Biochemistry, Nutrition Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran 2Professor of Clinical Biochemistry, Department of Biochemistry, Shahrood Branch, Islamic Azad University, Shahrood, Iran *Corresponding author: Mohamad Taghi Goodarzi, Abstract Department of Biochemistry, ANGPTL8, a new hormone, is regarded as a novel target for type-2 diabetes and associated metabolic Shahrood Branch, Islamic Azad University, Shahrood, disorder. Nutritional state and hormonal factors are involved in the regulation of ANGPTL-8 expression. Iran. This protein is associated with some myokines or adipokines. Several studies confirmed the function of Tel: +98 23 32390360 ANGPTL-8 in glucose metabolism and diabetes complications; however, there are opposite results. The Fax: +98 23 32390077 Email: mtgoodarzi@yahoo. accurate function of ANGPTL-8 in T2D remains unclear. Further strictly controlled studies including com measuring methods, nutritional state, diagnostic criteria of overweight/obesity, age, and ethnicity may help to resolve discrepancies. In addition, more studies are demanded to clarify the potential role of Received: 25 November 2019 ANGPTL-8 in humans, a cause or an effect of this protein in association with insulin resistance, the Accepted: 12 December 2019 ePublished: 30 December 2019 regulatory mechanism of ANGPTL-8 expression, and the association of ANGPTL8 with other adipokines or myokines. In this mini review, we described various roles of ANGPTL-8 in diabetes.
    [Show full text]
  • ANGPTL8/Betatrophin R59W Variant Is Associated with Higher Glucose
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector Abu-Farha et al. Lipids in Health and Disease (2016) 15:26 DOI 10.1186/s12944-016-0195-6 RESEARCH Open Access ANGPTL8/Betatrophin R59W variant is associated with higher glucose level in non-diabetic Arabs living in Kuwaits Mohamed Abu-Farha1*†, Motasem Melhem2†, Jehad Abubaker1, Kazem Behbehani1,2, Osama Alsmadi2 and Naser Elkum3* Abstract Background: ANGPTL8 (betatrophin) has been recently identified as a regulator of lipid metabolism through its interaction with ANGPTL3. A sequence variant in ANGPTL8 has been shown to associate with lower level of Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL). The objective of this study is to identify sequence variants in ANGPTL8 gene in Arabs and investigate their association with ANGPTL8 plasma level and clinical parameters. Methods: A cross sectional study was designed to examine the level of ANGPTL8 in 283 non-diabetic Arabs, and to identify its sequence variants using Sanger sequencing and their association with various clinical parameters. Results: Using Sanger sequencing, we sequenced the full ANGPTL8 gene in 283 Arabs identifying two single nucleotide polymorphisms (SNPs) Rs.892066 and Rs.2278426 in the coding region. Our data shows for the first time that Arabs with the heterozygote form of (c.194C > T Rs.2278426) had higher level of Fasting Blood Glucose (FBG) compared to the CC homozygotes. LDL and HDL level in these subjects did not show significant difference between the two subgroups. Circulation level of ANGPTL8 did not vary between the two forms.
    [Show full text]
  • The Circulating ANGPTL8 Levels Show Differences Among Novel Subgroups
    www.nature.com/scientificreports OPEN The circulating ANGPTL8 levels show diferences among novel subgroups of adult patients with diabetes and are associated with mortality in the subsequent 5 years Huajie Zou1, Wu Duan1,2, Zeqing Zhang1, Xi Chen1, Puhan Lu1 & Xuefeng Yu1* ANGPTL8, an important regulator of glucose and lipid metabolism, is associated with diabetes, but the role of ANGPTL8 in the outcomes of novel subgroups of diabetes remains unclear. To assess the circulating ANGPTL8 levels in novel subgroups of diabetes and their association with health outcomes, we performed a data-driven cluster analysis (k-means) of patients with newly diagnosed diabetes (741 patients enrolled from 2011 through 2016) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study. The primary outcomes were mortality from all causes and cardiovascular diseases (CVD), and the secondary outcome was any cardiovascular event. Comparisons among groups were performed using the Kruskal–Wallis test, and the correlations between variables were assessed using the Pearson correlation test. Logistic regression was used to detect associations between the risk of outcomes and the ANGPTL8 levels. We identifed four replicable clusters of patients with diabetes that exhibited signifcantly diferent patient characteristics and risks of all-cause mortality. The serum ANGPTL8 levels in the cluster of mild age-related diabetes (MARD), severe insulin-resistant diabetes (SIRD), and severe insulin-defcient diabetes (SIDD) were signifcantly higher than those in the mild obesity-related diabetes (MOD) cluster (685.01 ± 24.50 vs. 533.5 ± 18.39, p < 0.001; 649.69 ± 55.83 vs. 533.5 ± 18.39, = 0.040; 643.29 ± 30.89 vs.
    [Show full text]
  • The ANGPTL8 Rs2278426 (C/T) Polymorphism Is Associated with Prediabetes and Type 2 Diabetes in a Han Chinese Population in Hebei Province
    Hindawi International Journal of Endocrinology Volume 2020, Article ID 1621239, 8 pages https://doi.org/10.1155/2020/1621239 Research Article The ANGPTL8 rs2278426 (C/T) Polymorphism Is Associated with Prediabetes and Type 2 Diabetes in a Han Chinese Population in Hebei Province Guangsen Hou,1 Yong Tang,2 Luping Ren ,2 Yunpeng Guan,1 Xiaoyu Hou,1 and Guangyao Song 1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, China 2Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, China Correspondence should be addressed to Guangyao Song; [email protected] Received 1 July 2020; Revised 14 October 2020; Accepted 23 November 2020; Published 3 December 2020 Academic Editor: Pawel Grzmil Copyright © 2020 Guangsen Hou et al. ,is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Our aim was to investigate the association between the genetics of the angiopoietin protein-like 8 (ANGPTL8) rs2278426 (C/T) polymorphism with prediabetes (pre-DM) and type 2 diabetes (T2DM) in a Han Chinese population in Hebei Province, China. Methods. We enrolled 1,460 participants into this case-control study: healthy controls, n � 524; pre-DM, n � 460; and T2DM: n � 460. Ligase assays on blood samples from all participants were used to identify polymorphisms. Differences in genotype and allele distributions were compared by the chi-square test and one-way analysis of variance, and a post hoc pairwise analysis was performed using the Bonferroni test. ,e logistic regression technique was adjusted for age, sex, and body mass index.
    [Show full text]
  • ANGPTL8 Protein-Truncating Variant and the Risk of Coronary Disease, Type 2 Diabetes and Adverse Effects
    medRxiv preprint doi: https://doi.org/10.1101/2020.06.09.20125278; this version posted June 12, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . ANGPTL8 protein-truncating variant and the risk of coronary disease, type 2 diabetes and adverse effects Authors: Pyry Helkkula, MEng1, Tuomo Kiiskinen, MD1,2, Aki S. Havulinna, DSc (Tech)1,2, Juha Karjalainen, PhD1,3,4, Seppo Koskinen, MD, PhD2, Veikko Salomaa, MD, PhD2, FinnGen, Mark J. Daly, PhD1,3,4, Aarno Palotie, MD, PhD1,4,5, Ida Surakka, PhD1,6, Samuli Ripatti, PhD1,4,7† Affiliations: 1. Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland 2. Finnish Institute for Health and Welfare, Helsinki, Finland 3. Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA 4. Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA 5. Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Analytic and Translational Genetics Unit, Department of Medicine, and the Department of Neurology, Massachusetts General Hospital, Boston, MA, USA 6. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA 7. Department of Public Health, University of Helsinki, Helsinki, Finland †Corresponding author: Samuli Ripatti, PhD Institute for Molecular Medicine Finland, HiLIFE PO Box 20 FI-00014 University of Helsinki, Finland and Broad Institute of MIT and Harvard, Cambridge, MA +358 40 567 0826 [email protected] NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
    [Show full text]