DOCSLIB.ORG

Genetic and Neural Mechanisms Regulating the Interaction

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genetic and Neural Mechanisms Regulating the Interaction GENETIC AND NEURAL MECHANISMS REGULATING THE INTERACTION BETWEEN SLEEP AND METABOLISM IN DROSOPHILA MELANOGASTER by Maria E. Yurgel A Dissertation Submitted to the Faculty of The Charles E. Schmidt College of Science In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Florida Atlantic University Boca Raton, FL December 2018 Copyright 2018 by Maria Eduarda Yurgel ii GENETIC AND NEURAL MECHANISMS REGULATING THE INTERACTION BETWEEN SLEEP AND METABOLISM IN DROSOPHILAMELANOGASTER by Maria E. Yurgel This dissertation was prepared under the direction of the candidate's dissertation advisor, Dr. Alex C. Keene, Department of Biological Sciences, and has been approved by the members of her supervisory committee. It was submitted to the faculty of the Charles E. Schmidt College of Science and was accepted in partial fulfillmentof the requirements for the degree of Doctor of Philosophy. SUPERVISORY COMMITTEE: Z!--�•r<. �� --- Alex C. Keene, Ph.D. Disserta · n Advis ,,. Tanja Godenschwege, Ph.p Khaled Sobhan, Ph.D. Date� 7 Interim Dean, Graduate College 111 ACKNOWLEDGEMENTS I would like to express my gratitude for all my committee members for their guidance and support. First and foremost, I would like to thank my mentor, Dr. Alex Keene, for believing in my potential and giving me the opportunity to pursue my PhD in his laboratory. During these 5 years, I have been challenged to my limit and pushed to think, to be creative, and be productive. His passion and excitement for science fueled me to get out of my comfort zone, implement new techniques, and pursue questions that were not trivial. I am also greatly indebted to Dr. Tanja Godenschwege, for helping me both scientifically and personally through the highs and lows of my graduate education. Her extensive knowledge and thirst for new challenges made me appreciate research. I will be forever thankful for her always welcoming my questions, providing thoughtful advice, and above all, instilling a newfound confidence in myself. I also would like to thank Dr. Greg Macleod for always providing experimental guidance and making me think outside the box. I am greatly indebted to Dr. Rod Murphey for creating an ideal environment for scientific pursuits and being extremely supportive of all graduate students. Finally, I have been lucky to have an informal advisor, Erik Duboue, who has always welcomed my questions and provided thoughtful experimental and career advice. Moving from the University of Nevada, Reno to Florida Atlantic University was not an easy transition. I am eternally appreciative of my labmates and good friends, Kazuma Murakami, James Jaggard, Melissa Slocumb, and Beatriz Robinson who made this journey enjoyable. Without their help and support I would not have succeeded. iv The work presented in this dissertation would not have been possible without the environment in the Keene lab. I wanted to thank all lab members for their patience, willingness to help, and support through the many ups and downs of graduate life. In particular, I wanted to express my deepest gratitude to John Tauber. His wit for research, incredible talent, perseverance, and critical eye has challenged me to do better and be better. I am also thankful to Kreesha Shah, without her help my last year in lab would not have gone smoothly. Lastly, I am thankful to the post docs in the Keene Lab including Pavel Masek, Masato Yoshizawa, Bethany Stahl, and Elizabeth Brown. In particular, Elizabeth for being an incredible labmate, always willing to help and brainstorm with me. There are innumerable graduate students and staff members of MC-19 that have been critical during my PhD. I would like to thank the members of the Macleod, Godenschwege, Duboue, Stackman, and Murphey Labs. In particular, I want to thank Jana Boerner for her collaborative work and patience to teach me microscopy. Finally, I would like to thank Silvana Jaramillo and Dr. Stacee Caplan for going above and beyond to help me with administrative issues throughout my PhD. Above all, I would like to thank my family for their love and support. Their emphasis in education, culture, and knowledge is truly unprecedented, you are my inspiration. My mother and father have taught me from a young age to be persistent and move through life with an ambitious mind. I will be forever thankful for their support in every single decision in my life. My grandfather, Henrique, grandmothers, Maria Helena and Adelia, and aunt, Maria Laura, for their unconditional love. Your love has grounded me and given me strength and inspiration to reach my life goals. My sister, Martina, her clever sense of humor, understanding and protective nature, has made life easier and v more enjoyable. I am eternally grateful for her support. I would like to thank all my cousins for always giving me advice and supporting who I am, especially, Caio and Marcela. Both of you have set a bar unreachably high both academically and personally and I am constantly looking up to both of you. Finally, I would like to thank my partner, Paloma Amaral. Her love and support have given me the strength to carry on. I am honored to have you by my side. I am also very grateful for all the help she has given me in the lab, both experimentally and in editing my thesis. Throughout my life I have been very lucky to have met incredible friends who have gone lengths to help me. I would like to thank my college friend, Kathryn Zingaro, for her loyalty and support throughout this endeavor. I am also greatly indebted to Veronica Arinze, who showed me the fun side of life. Also, Ed and Gail Greenberg for taking the time to read my thesis and being supportive in every aspect of my personal and professional life. I would like to thank my mentor, Daniela Vilas Boas, for her invaluable guidance. Lastly, I thank my tennis coach, Mauro Brandao, for teaching me to be perseverant. vi ABSTRACT Author: Maria Eduarda Yurgel Title: GENETIC AND NEURAL MECHANISMS REGULATING THE INTERACTION BETWEEN SLEEP AND METABOLISM IN DROSOPHILA MELANOGASTER Institution: Florida Atlantic University Dissertation Advisor: Dr. Alex C. Keene Degree: Doctor of Philosophy Year: 2018 Dysregulation of sleep and metabolism has enormous health consequences. Sleep loss is linked to increased appetite and insulin insensitivity, and epidemiological studies link chronic sleep deprivation to obesity-related disorders. Interactions between sleep and metabolism involve the integration of signalling from brain regions regulating sleep, feeding, and metabolism, as well as communication between the brain and peripheral organs. In this series of studies, using the fruit fly as a model organism, we investigated how feeding information is processed to regulate sleep, and how peripheral tissues regulate sleep through the modulation of energy stores. In order to address these questions, we performed a large RNAi screen to identify novel genetic regulators of sleep and metabolism. We found that, the mRNA/DNA binding protein, Translin (trsn), is necessary for the acute modulation of sleep in accordance with feeding state. Flies mutant for trsn or selective knockdown of trsn in Leucokinin (Lk) neurons abolishes starvation-induced sleep suppression. In addition, vii genetic silencing of Lk neurons or a mutation in the Lk locus also disrupts the integration between sleep and metabolism, suggesting that Lk neurons are active during starvation. We confirmed this hypothesis by measuring baseline activity during fed and starved states. We found that LHLK neurons, which have axonal projections to sleep and metabolic centers of the brain, are more active during starvation. These findings suggest that LHLK neurons are modulated in accordance with feeding state to regulate sleep. Finally, to address how peripheral tissues regulate sleep, we performed an RNAi screen, selectively knocking down genes in the fat body. We found that knockdown of Phosphoribosylformylglycinamidine synthase (Ade2), a highly conserved gene involved the biosynthesis of purines, regulates sleep and energy stores. Flies heterozygous for two Ade2 mutations are short sleepers and this effect is partially rescued by restoring Ade2 to the fly fat body. These findings suggest Ade2 functions within the fat body to promote both sleep and energy storage, providing a functional link between these processes. Together, the experimental evidence presented here provides an initial model for how the peripheral tissues communicate to the brain to modulate sleep in accordance with metabolic state. viii GENETIC AND NEURAL MECHANISMS REGULATING THE INTERACTION BETWEEN SLEEP AND METABOLISM IN DROSOPHILA MELANOGASTER LIST OF TABLES ........................................................................................................... xiii LIST OF FIGURES ......................................................................................................... xiv CHAPTER 1. LITERATURE REVIEW ............................................................................ 1 Introduction ..................................................................................................................... 1 Why do we sleep? ........................................................................................................... 2 How sleep is regulated in mammals? .............................................................................. 3 Food intake and energy expenditure in mammals ........................................................... 7 Mechanisms for sleep-metabolism interactions in mammals ........................................
Load more

Recommended publications
  • Using Drosophila to Discover Mechanisms Underlying Type 2 Diabetes Ronald W
    © 2016. Published by The Company of Biologists Ltd | Disease Models & Mechanisms (2016) 9, 365-376 doi:10.1242/dmm.023887 REVIEW SUBJECT COLLECTION: TRANSLATIONAL IMPACT OF DROSOPHILA Using Drosophila to discover mechanisms underlying type 2 diabetes Ronald W. Alfa1,2,* and Seung K. Kim1,3,4,* ABSTRACT phenotypes (Dimas et al., 2014; Frayling and Hattersley, 2014; Mechanisms of glucose homeostasis are remarkably well conserved Renström et al., 2009). Nonetheless, major challenges remain in between the fruit fly Drosophila melanogaster and mammals. From translating GWAS associations into mechanistic and clinically the initial characterization of insulin signaling in the fly came the translatable insights (McCarthy et al., 2008). As discovery of identification of downstream metabolic pathways for nutrient storage disease-associated single-nucleotide polymorphisms (SNPs) and utilization. Defects in these pathways lead to phenotypes that are continues, these SNPs first need to be causally associated with analogous to diabetic states in mammals. These discoveries have individual genes. Once gene candidates are identified, the gold- stimulated interest in leveraging the fly to better understand the standard for characterizing the molecular mechanisms of disease genetics of type 2 diabetes mellitus in humans. Type 2 diabetes alleles and the role of individual genes in metabolic disease is results from insulin insufficiency in the context of ongoing insulin experimental interrogation in model organisms (McCarthy et al., resistance. Although genetic susceptibility is thought to govern the 2008). This task can present a formidable challenge considering that propensity of individuals to develop type 2 diabetes mellitus under SNPs might cause gain of function, loss of function or reflect tissue- appropriate environmental conditions, many of the human genes specific effects.
    [Show full text]
  • Supplementary Materials File Recent Advances In
    1 Supplementary Materials file Appendix 1 Recent advances in neuropeptide signaling in Drosophila, from genes to physiology and behavior Dick R. Nässel1 and Meet Zandawala Brief overview of Drosophila neuropeptides and peptide hormones (Appendix to section 5) Contents 5. 1. Adipokinetic hormone (AKH) 5. 2. Allatostatin-A (Ast-A) 5. 3. Allatostatin-B (Ast-B), or myoinhibitory peptide (MIP) 5. 4. Allatostatin-C (Ast-C) 5. 5. Allatostatin-CC (Ast-CC) or allatostatin double C 5. 6. Bursicon and partner of bursicon, or bursicon a and b 5. 7. Capability (Capa), a precursor encoding periviscerokinins and a pyrokinin 5. 8. CCHamide-1 and CCHamide-2 are encoded by separate genes 5. 9. CNMamide 5. 10. Corazonin (CRZ) 5. 11. Crustacean cardioactive peptide (CCAP) 5. 12. Diuretic hormone 31 (DH31), or calcitonin-like diuretic hormone 5. 13. Diuretic hormone 44 (DH44) 5. 14. Ecdysis-triggering hormone (ETH) and pre-ecdysis-triggering hormone (PETH) 5. 15. Eclosion hormone (EH) 5. 16. FMRFamide (FMRFa), or extended FMRFamides 5. 17. Glycoprotein A2 (GPA2) and Glycoprotein B5 (GPB5) 5. 18. Insulin-like peptides (ILPs), encoded by multiple genes 5. 19. Ion-transport peptide (ITP) 5. 20. Leucokinin (LK) or kinins (insectakinins) 5. 21. Limostatin 2 5. 22. Myosuppressin (Dromyosuppressin, DMS) 5. 23. Natalisin 5. 24. Neuropeptide F (NPF) 5. 25. Neuropeptide-like precursors 5. 25. 1. Neuropeptide-like precursor 1 (NPLP1) 5. 25. 2. Neuropeptide-like precursor 2 (NPLP2) 5. 25. 3. Neuropeptide-like precursor 3 (NPLP3) 5. 25. 4. Neuropeptide-like precursor 4 (NPLP4) 5. 26. Orcokinin (OK) 5. 27. Pigment-dispersing factor (PDF) 5.
    [Show full text]
  • Peninsula Laboratories International, Inc
    PENINSULA LABORATORIES INTERNATIONAL, INC. ProductNumberName Amount Unit H-4952.0010 ([125I]-Tyr)-Angiotensin II, CE-marked, Liquid 10 µCi H-4954.0010 ([125I]-Tyr0)-Bradykinin, CE-marked, Liquid 10 µCi H-4956.0010 ([125I]-Tyr)-Calcitonin (salmon I), CE-marked, Liquid 10 µCi H-4958.0010 ([125I]-Tyr0)-a-CGRP (mouse, rat), CE-marked, Liquid 10 µCi H-4962.0010 ([125I]-Tyr0)-CRF (human, mouse, rat), CE-marked, Liquid 10 µCi H-4964.0010 ([125I]-Tyr)-Endothelin-1 (human, bovine, dog, mouse, porcine, rat), CE-marked, Liquid 10 µCi H-4966.0010 ([125I]-Tyr)-GLP-1 (7-36) amide (human, bovine, guinea pig, mouse, rat), CE-marked, Liquid 10 µCi H-4968.0010 ([125I]-Tyr)-(Des-Gly10,D-Leu6,Pro-NHEt9)-LHRH, CE-marked, Liquid 10 µCi H-4972.0010 ([125I]-Tyr)-(Des-Gly10,D-Trp6,Pro-NHEt9)-LHRH, CE-marked, Liquid 10 µCi H-4974.0010 ([125I]-Tyr)-Orexin A (human, bovine, canine, mouse, ovine, porcine, rat), CE-marked, Liquid 10 µCi H-4976.0010 ([125I]-Tyr)-Oxytocin, CE-marked, Liquid 10 µCi H-4978.0010 ([125I]-Tyr0)-pTH (1-34) (human), CE-marked, Liquid 10 µCi H-5004.0010 ([125I]-Tyr)-ACTH (1-39) (mouse, rat), CE-marked, Liquid 10 µCi H-5006.0010 ([125I]-Tyr)-Atrial Natriuretic Factor (1-28) (mouse, rabbit, rat), CE-marked, Liquid 10 µCi H-5008.0010 ([125I]-Tyr0)-BNP-32 (human), CE-marked, Liquid 10 µCi H-5012.0010 ([125I]-Tyr)-b-Endorphin (human), CE-marked, Liquid 10 µCi H-5016.0010 ([125I]-Tyr)-Gastric Inhibitory Polypeptide (human), CE-marked, Liquid 10 µCi H-5018.0010 ([125I]-Tyr)-Pancreatic Polypeptide (human), CE-marked, Liquid 10 µCi H-5022.0010 ([125I]-Tyr)-Peptide
    [Show full text]
  • Neuroendocrine Cancer: Genomics of Phaeochromocytomas And
    RESEARCH HIGHLIGHTS Nature Reviews Endocrinology 11, 194 (2015); published online 17 February 2015; doi:10.1038/nrendo.2015.19; doi:10.1038/nrendo.2015.20; IN BRIEF doi:10.1038/nrendo.2015.21; doi:10.1038/nrendo.2015.22 OBESITY New pathway in the distribution of body fat identified Mutations in genes encoding WNT co-receptors, LPR5 and LPR6, are known to be associated with cardiometabolic disorders. A team of researchers has now investigated the role of LPR5 in adipose tissue. They found that patients with gain-of-function mutations had increased fat accumulation in the lower body, whereas a common LPR5 allele (rs599083) was associated with increased abdominal accumulation of fat. Furthermore, LPR5 expression was higher in abdominal adipocyte progenitors than in gluteal adipocyte progenitor cells and knockdown of the gene in the two progenitor cell populations led to different outcomes in fat distribution. Original article Loh, N. Y. et al. LRP5 regulates human body fat distribution by modulating adipose progenitor biology in a dose- and depot-specific fashion. Cell Metab. 21, 262–272 (2015) METABOLISM Limostatin—a decretin—suppresses insulin production Experiments in Drosophila melanogaster have revealed that limostatin, a peptide hormone, suppresses insulin production and secretion and can therefore be classed as a decretin hormone. Flies that lacked limostatin displayed features similar to hyperinsulinaemia, hypoglycaemia and increased adiposity. The researchers suggest that neuromedin U receptors are a human orthologue for limostatin, as NMRU1 is expressed in human islet β cells and purified neuromedin U suppressed insulin section in isolated human β cells. Original article Alfa, R. W.
    [Show full text]
  • Metabolism and Growth Adaptation to Environmental Conditions in Drosophila
    Cellular and Molecular Life Sciences (2020) 77:4523–4551 https://doi.org/10.1007/s00018-020-03547-2 Cellular andMolecular Life Sciences REVIEW Metabolism and growth adaptation to environmental conditions in Drosophila Takashi Koyama1 · Michael J. Texada1 · Kenneth A. Halberg1 · Kim Rewitz1 Received: 16 December 2019 / Revised: 19 April 2020 / Accepted: 11 May 2020 / Published online: 24 May 2020 © The Author(s) 2020 Abstract Organisms adapt to changing environments by adjusting their development, metabolism, and behavior to improve their chances of survival and reproduction. To achieve such fexibility, organisms must be able to sense and respond to changes in external environmental conditions and their internal state. Metabolic adaptation in response to altered nutrient availability is key to maintaining energy homeostasis and sustaining developmental growth. Furthermore, environmental variables exert major infuences on growth and fnal adult body size in animals. This developmental plasticity depends on adaptive responses to internal state and external cues that are essential for developmental processes. Genetic studies have shown that the fruit fy Drosophila, similarly to mammals, regulates its metabolism, growth, and behavior in response to the environment through several key hormones including insulin, peptides with glucagon-like function, and steroid hormones. Here we review emerg- ing evidence showing that various environmental cues and internal conditions are sensed in diferent organs that, via inter- organ communication, relay information to neuroendocrine centers that control insulin and steroid signaling. This review focuses on endocrine regulation of development, metabolism, and behavior in Drosophila, highlighting recent advances in the role of the neuroendocrine system as a signaling hub that integrates environmental inputs and drives adaptive responses.
    [Show full text]
  • Regulation of Body Size and Growth Control
    | FLYBOOK DEVELOPMENT AND GROWTH Regulation of Body Size and Growth Control Michael J. Texada, Takashi Koyama, and Kim Rewitz1 Department of Biology, University of Copenhagen, 2100, Denmark ORCID IDs: 0000-0003-2551-3059 (M.J.T.); 0000-0003-4203-114X (T.K.); 0000-0002-4409-9941 (K.R.) ABSTRACT The control of body and organ growth is essential for the development of adults with proper size and proportions, which is important for survival and reproduction. In animals, adult body size is determined by the rate and duration of juvenile growth, which are influenced by the environment. In nutrient-scarce environments in which more time is needed for growth, the juvenile growth period can be extended by delaying maturation, whereas juvenile development is rapidly completed in nutrient-rich conditions. This flexibility requires the integration of environmental cues with developmental signals that govern internal checkpoints to ensure that maturation does not begin until sufficient tissue growth has occurred to reach a proper adult size. The Target of Rapamycin (TOR) pathway is the primary cell-autonomous nutrient sensor, while circulating hormones such as steroids and insulin-like growth factors are the main systemic regulators of growth and maturation in animals. We discuss recent findings in Drosophila melanogaster showing that cell-autonomous environment and growth-sensing mechanisms, involving TOR and other growth-regulatory pathways, that converge on insulin and steroid relay centers are responsible for adjusting systemic growth, and development, in response to external and internal conditions. In addition to this, proper organ growth is also monitored and coordinated with whole-body growth and the timing of maturation through modulation of steroid signaling.
    [Show full text]
  • Hipoglikemia
    i DR. Dr. Andi Makbul Aman, SpPD, K-EMD, FINASIM HIPOGLIKEMIA DALAM PRAKTIK SEHARI-HARI ii HIPOGLIKEMIA DALAM PRAKTIK SEHARI-HARI Penulis : Andi Makbul Aman Mansyur ISBN : 978-602-61363-4-3 Diterbitkan Oleh : Departemen Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Hasanuddin 2018 Hak Cipta Dilindungi Undang-Undang : Dilarang memperbanyak, mencetak dan menerbitkan sebagian atau seluruh isi buku ini dengan cara dan bentuk apapun tanpa seizin penulis dan penerbit iii Pengantar dari Penulis Hipoglikemia merupakan kondisi klinis yang ditandai oleh penurunan kadar glukosa darah melewati ambang batas yang bisa ditoleransi oleh tubuh. Hipoglikemia sering dijumpai dalam praktek sehari-hari, baik pada pasien rawat jalan maupun pasien rawat inap di rumah sakit. Bila tidak terdeteksi dan tidak mendapat terapi dengan cepat akan menimbulkan konsekwensi dan komplikasi yang serius. Kualitas hidup pasien hipoglikemia terutama yang berulang akan menurun, menyebabkan kerusakan otak ringan hingga permanen bahkan dapat menjadi pemicu terjadinya penyakit jantung koroner dan kematian secara mendadak. Tujuan penulisan buku ini adalah untuk memberikan informasi lengkap tentang definisi, prevalensi, jenis dan klasifikasi serta dampak dari hipoglikemia, baik untuk pasien diabetes melitus maupun untuk pasien non-diabetes. Dipaparkan pula tentang tatacara diagnosis dan terapi dari hipoglikemia. Penulis menyampaikan terima kasih kepada semua pihak yang telah membantu mulai saat merancang hingga tahap penulisan buku ini selesai. Ucapan terima kasih terutama penulis haturkan kepada Bapak Prof. Dr. dr. Ahmad Rudijanto, SpPD, K-EMD, FINASIM selaku ketua umum PB. PERKENI periode tahun 2012-2015 dan 2015-2018 atas dukungan serta kesediannya untuk memberikan kata sambutan pada buku ini. Demikian pula kepada Bapak Prof. Dr.dr. H. Syakib Bakri, SpPD, K-GH, FINASIM yang senantiasa memberikan gagasan, semangat, bantuan literatur serta saran dan koreksi sehingga buku ini berhasil diterbitkan.
    [Show full text]
  • Fat Body—Multifunctional Insect Tissue
    insects Review Fat Body—Multifunctional Insect Tissue Patrycja Skowronek *, Łukasz Wójcik and Aneta Strachecka Department of Zoology and Animal Ecology, University of Life Sciences in Lublin, Akademicka 13, 20-950 Lublin, Poland; [email protected] (Ł.W.); [email protected] (A.S.) * Correspondence: [email protected] Simple Summary: Efficient and proper functioning of processes within living organisms play key roles in times of climate change and strong human pressure. In insects, the most abundant group of organisms, many important changes occur within their tissues, including the fat body, which plays a key role in the development of insects. Fat body cells undergo numerous metabolic changes in basic energy compounds (i.e., lipids, carbohydrates, and proteins), enabling them to move and nourish themselves. In addition to metabolism, the fat body is involved in the development of insects by determining the time an individual becomes an adult, and creates humoral immunity via the synthesis of bactericidal proteins and polypeptides. As an important tissue that integrates all signals from the body, the processes taking place in the fat body have an impact on the functioning of the entire body. Abstract: The biodiversity of useful organisms, e.g., insects, decreases due to many environmental factors and increasing anthropopressure. Multifunctional tissues, such as the fat body, are key ele- ments in the proper functioning of invertebrate organisms and resistance factors. The fat body is the center of metabolism, integrating signals, controlling molting and metamorphosis, and synthesizing hormones that control the functioning of the whole body and the synthesis of immune system Citation: Skowronek, P.; Wójcik, Ł.; proteins.
    [Show full text]
  • Drosophila As a Model to Study Obesity and Metabolic Disease Laura Palanker Musselman1,* and Ronald P
    © 2018. Published by The Company of Biologists Ltd | Journal of Experimental Biology (2018) 221, jeb163881. doi:10.1242/jeb.163881 REVIEW Drosophila as a model to study obesity and metabolic disease Laura Palanker Musselman1,* and Ronald P. Kühnlein2,3 ABSTRACT environmental and lifestyle factors in the etiology of obesity and Excess adipose fat accumulation, or obesity, is a growing problem obesity-related co-morbidities are still poorly understood. Given the worldwide in terms of both the rate of incidence and the severity of inherent genetic heterogeneity of human populations, animal obesity-associated metabolic disease. Adipose tissue evolved in models such as mice and flies are of particular value to animals as a specialized dynamic lipid storage depot: adipose cells disentangle the roles of nurture and nature in fat accumulation and synthesize fat (a process called lipogenesis) when energy is plentiful homeostasis. and mobilize stored fat (a process called lipolysis) when energy is Researchers began to develop an interest in employing needed. When a disruption of lipid homeostasis favors increased fat Drosophila melanogaster (hereafter called simply Drosophila)as synthesis and storage with little turnover owing to genetic a model system for obesity research in the early 1960s after the predisposition, overnutrition or sedentary living, complications such pioneering work of Dr Winifred Doane, who isolated the first obese as diabetes and cardiovascular disease are more likely to arise. The fly mutant called adipose from a Nigerian wild population. adipose vinegar fly Drosophila melanogaster (Diptera: Drosophilidae) is used mutant flies suffer from excessive fat storage but reduced as a model to better understand the mechanisms governing fat carbohydrate reserves (Doane, 1961, 1960a,b).
    [Show full text]
  • Regulation of Endoplasmic Reticulum Stress in Adipose
    University of Warwick institutional repository: http://go.warwick.ac.uk/wrap A Thesis Submitted for the Degree of PhD at the University of Warwick http://go.warwick.ac.uk/wrap/74256 This thesis is made available online and is protected by original copyright. Please scroll down to view the document itself. Please refer to the repository record for this item for information to help you to cite it. Our policy information is available from the repository home page. Regulation of Endoplasmic Reticulum Stress in Adipose Tissue Metabolism By Philip Demos Voyias, BSc Hons A thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Medical Sciences Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick June 2015 1 Table of Contents Abbreviations ....................................................................................................... 8 List of tables ........................................................................................................ 15 List of figures ...................................................................................................... 15 Acknowledgements ............................................................................................. 18 Declaration .......................................................................................................... 20 List of publications ............................................................................................. 21 Abstract ..............................................................................................................
    [Show full text]
  • Regulation of Insulin and Adipokinetic Hormone/Glucagon Production in Flies
    Received: 26 March 2019 Revised: 28 June 2019 Accepted: 9 July 2019 DOI: 10.1002/wdev.360 ADVANCED REVIEW Regulation of insulin and adipokinetic hormone/glucagon production in flies Muhammad Ahmad1 |LiHe1 | Norbert Perrimon1,2 1Department of Genetics, Harvard Medical School, Boston, Massachusetts Abstract 2Howard Hughes Medical Institute, Harvard Metabolic homeostasis is under strict regulation of humoral factors across various Medical School, Boston, Massachusetts taxa. In particular, insulin and glucagon, referred to in Drosophila as Drosophila insulin-like peptides (DILPs) and adipokinetic hormone (AKH), respectively, are Correspondence Norbert Perrimon, Department of Genetics, key hormones that regulate metabolism in most metazoa. While much is known Harvard Medical School, Boston, MA about the regulation of DILPs, the mechanisms regulating AKH/glucagon produc- 02115. tion is still poorly understood. In this review, we describe the various factors that Email: [email protected] regulate the production of DILPs and AKH and emphasize the need for future studies Funding information to decipher how energy homeostasis is governed in Drosophila. National Institute of Diabetes and Digestive and Kidney Diseases, Grant/Award Number: This article is categorized under: R01DK121409 Invertebrate Organogenesis > Flies Signaling Pathways > Global Signaling Mechanisms KEYWORDS AKH, Drosophila, hormone, insulin 1 | INTRODUCTION Insulin and glucagon are key mammalian hormones produced from pancreatic islet cells that regulate the mobilization of fat and glucose in an antagonistic fashion (Freychet, 1990; Ganong, 1991). Under high blood sugar conditions, pancreatic β-cells release insulin, which in turn triggers glucose accumulation in the form of glycogen synthesis. Under low blood sugar conditions, insulin is repressed and pancreatic α-cells release glucagon, which triggers the breakdown of glycogen to free sugars.
    [Show full text]
  • NIDDK Recent Advances and Emerging Opportunities
    Up to half of people with diabetes suffer damage to nerves throughout the body, damage that can lead to decreased sensation, difficulty moving, and pain and tingling in arms, legs, hands, and feet—a condition called diabetic sensorimotor polyneuropathy, or DSPN. Neuropathy is a major risk factor for amputation. Because the earliest signs of nerve damage occur in small nerves, tools to assess small nerve damage are critical for detecting and developing new therapies for DSPN. Currently, the most reliable tool for assessing small nerve damage is an invasive skin biopsy. A noninvasive technique to measure small nerve damage has the potential to improve the ability to detect and monitor DSPN early and to speed research to develop new approaches to prevent and treat it. Research described in this chapter indicates that a noninvasive laser-based imaging technique called corneal confocal microscopy (CCM), which allows users to image small nerves in the front of a person’ s eye, could be a new tool for detecting DSPN. The three panels above show CCM images of nerve fibers (white) in the eyes of three study participants. Compared to a person without diabetes (left) and a person with type 1 diabetes but no DSPN (middle), a person with type 1 diabetes and DSPN (right) has lower nerve fiber density, as illustrated by fewer arrows pointing to main (red arrow) and branch (yellow arrow) nerve fibers. As described in the chapter, both CCM and the invasive skin biopsy technique were similarly effective for diagnosing DSPN. These new findings suggest that the noninvasive nature of CCM, as well as its potential for automation, could make it preferable to skin biopsy for detecting DSPN.
    [Show full text]