EDITED BY
Suzanne L. Dickson
The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Julian G. Mercer
The Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK
This edition first published 2016
© 2016 John Wiley & Sons, Ltd
Registered Office
John Wiley & Sons, Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, United Kingdom
For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com.
The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.
Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book.
Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. It is sold on the understanding that the publisher is not engaged in rendering professional services and neither the publisher nor the author shall be liable for damages arising herefrom. If professional advice or other expert assistance is required, the services of a competent professional should be sought.
Library of Congress Cataloging-in-Publication Data
Names: Dickson, Suzanne L., editor. | Mercer, Julian G., editor.
Title: Neuroendocrinology of appetite / [edited by] Suzanne L Dickson, Julian G Mercer.
Description: Chichester, West Sussex ; Hoboken : John Wiley & Sons Inc., 2016. | Includes bibliographical references and index.
Identifiers: LCCN 2016022665| ISBN 9781118839324 (cloth) | ISBN 9781118839287 (Epdf) | ISBN 9781118839300 (Epub) | ISBN 9781118839317 (Obook)
Subjects: | MESH: Appetite Regulation–physiology | Neurosecretory Systems–anatomy & histology | Feeding and Eating Disorders–therapy
Classification: LCC RC552.E18 | NLM WI 102 | DDC 616.85/2606–dc23
LC record available at https://lccn.loc.gov/2016022665
A catalogue record for this book is available from the British Library.
Deniz Atasoy
Istanbul Medipol University
Istanbul, Turkey
Udo Bauer
AstraZeneca R&D Mölndal
Mölndal, Sweden
Sebastien G. Bouret
The Saban Research Institute
Developmental Neuroscience Program, Children’s Hospital Los Angeles
University of Southern California
Los Angeles, California, USA;
INSERM, Jean-Pierre Aubert Research Center
University of Lille
Lille, France
Sophie Croizier
The Saban Research Institute
Developmental Neuroscience Program, Children’s Hospital Los Angeles
University of Southern California
Los Angeles, California, USA;
INSERM, Jean-Pierre Aubert Research Center
University of Lille
Lille, France
Stephan Hjorth
Department of Molecular and Clinical Medicine
Institute of Medicine
The Sahlgrenska Academy at the University of Gothenburg
Gothenburg, Sweden
Jens Juul Holst
Department of Biomedical Sciences
Faculty of Health Sciences
University of Copenhagen
Copenhagen, Denmark
Tara Jois
Department of Physiology
Biomedicine Discovery Institute
Monash University
Clayton, Victoria, Australia
Scott E. Kanoski
Department of Biological Sciences
University of Southern California
Los Angeles, California, USA
Susanne La Fleur
Department of Endocrinology and Metabolism
Laboratory of Endocrinology
University of Amsterdam
Amsterdam, The Netherlands
Wolfgang Langhans
Physiology and Behaviour Laboratory
Institute of Food, Nutrition and Health
ETH Zurich
Schwerzenbach, Switzerland
Carel le Roux
Diabetes Complications Research Centre
UCD Conway Institute
School of Medicine and Medical Science
University College Dublin
Dublin, Ireland
Anders Lehmann
Division of Endocrinology
Department of Physiology
Institute of Neuroscience and Physiology
The Sahlgrenska Academy at the University of Gothenburg
Gothenburg, Sweden
Rudolph L. Leibel
Division of Molecular Genetics, Department of Pediatrics and Naomi Berrie Diabetes Center
Columbia University
College of Physicians and Surgeons
New York, NY, USA
Gareth Leng
Centre for Integrative Physiology
University of Edinburgh
Edinburgh, UK
John Menzies
Centre for Integrative Physiology
University of Edinburgh
Edinburgh, UK
Mathieu Méquinion
Univ. Lille, INSERM, CHU Lille,
UMR-S 1172 - JPArc - Centre de Recherche
Jean-Pierre AUBERT Neurosciences et Cancer
Lille, France;
Department of Physiology Faculty of Medicine, Monash University Melbourne, Victoria, Australia
Paul N. Mirabella
Department of Physiology
Monash University
Melbourne, Victoria, Australia
Timothy H. Moran
Department of Psychiatry and Behavioral Sciences
Johns Hopkins University School of Medicine
Baltimore, Maryland, USA;
Johns Hopkins Global Obesity Prevention Center
Johns Hopkins University School of Medicine Baltimore, Maryland, USA
Karl Neff
Diabetes Complications Research Centre
UCD Conway Institute
School of Medicine and Medical Science
University College Dublin
Dublin, Ireland
Brian J. Oldfield
Department of Physiology
Monash University
Melbourne, Victoria, Australia
Hubert Preissl
Institute for Diabetes Research and Metabolic
Diseases of the Helmholtz Center Munich at the University of Tübingen
Tübingen, Germany
Michael Rosenbaum
Division of Molecular Genetics, Department of Pediatrics and Naomi Berrie Diabetes Center
Columbia University
College of Physicians and Surgeons
New York, NY, USA
Nancy Sabatier
Centre for Integrative Physiology
University of Edinburgh
Edinburgh, UK
Karolina P. Skibicka
Department of Physiology/Metabolic Physiology
Institute of Neuroscience and Physiology
The Sahlgrenska Academy at the University of Gothenburg
Gothenburg, Sweden
Mark W. Sleeman
Departments of Physiology and Biochemistry and Molecular Biology
Biomedicine Discovery Institute
Monash University
Clayton, Victoria, Australia
Paul A.M. Smeets
Image Sciences Institute
University Medical Center Utrecht
Utrecht, The Netherlands and
Division of Human Nutrition
Wageningen University and Research Centre
Wageningen, The Netherlands
Aneta Stefanidis
Department of Physiology
Monash University
Melbourne, Victoria, Australia
Scott M. Sternson
Janelia Research Campus
Howard Hughes Medical Institute
Ashburn, Virginia, USA
Yada Treesukosol
Department of Psychiatry and Behavioral Sciences
Johns Hopkins University School of Medicine
Baltimore, Maryland, USA
Odile Viltart
Univ. Lille, INSERM, CHU Lille,
UMR-S 1172 - JPArc - Centre de Recherche
Jean-Pierre AUBERT Neurosciences et Cancer
Lille, France
This Series is a joint venture between the International Neuroendocrine Federation and Wiley-Blackwell. The broad aim of the Series is to provide established researchers, trainees, and students with authoritative up-to-date accounts of the present state of knowledge, and prospects for the future across a range of topics in the burgeoning field of neuroendocrinology. The Series is aimed at a wide audience as neuroendocrinology integrates neuroscience and endocrinology. We define neuroendocrinology as the study of the control of endocrine function by the brain and the actions of hormones on the brain. It encompasses study of normal and abnormal function, and the developmental origins of disease. It includes study of the neural networks in the brain that regulate and form neuroendocrine systems. It also includes study of behaviors and mental states that are influenced or regulated by hormones. It necessarily includes understanding and study of peripheral physiological systems that are regulated by neuroendocrine mechanisms. Clearly, neuroendocrinology embraces many current issues of concern to human health and well-being, but research on these issues necessitates reductionist animal models.
Contemporary research in neuroendocrinology involves use of a wide range of techniques and technologies, from subcellular to systems and whole-organism level. A particular aim of the Series is to provide expert advice and discussion about experimental or study protocols in research in neuroendocrinology, and to further advance the field by giving information and advice about novel techniques, technologies, and interdisciplinary approaches.
To achieve our aims each book is on a particular theme in neuroendocrinology, and for each book we have recruited an editor, or pair of editors, expert in the field, and they have engaged an international team of experts to contribute Chapters in their individual areas of expertise. Their mission was to give an up-date of knowledge and recent discoveries, to discuss new approaches, ‘gold-standard’ protocols, translational possibilities, and future prospects. Authors were asked to write for a wide audience to minimize references, and to consider use of video clips and explanatory text boxes; each Chapter is peer-reviewed, and has a Glossary, and each book has a detailed index. We have been guided by an Advisory Editorial Board. The Masterclass Series is open-ended; books in the Series published to date are: Neurophysiology of Neuroendocrine Neurons (2014, eds W.E. Armstrong and J.G. Tasker), Neuroendocrinology of Stress (2015, eds J.A. Russell and M.J. Shipston), Molecular Neuroendocrinology: From Genome to Physiology (2016, eds D. Murphy and H. Gainer); Computational Neuroendocrinology (eds D.J. Macgregor and G. Leng). Books in preparation include The GnRH Neuron and its Control.
Feedback and suggestions are welcome.
John A. Russell, University of Edinburgh,
and William E. Armstrong, University of Tennessee
Advisory Editorial Board:
Ferenc A. Antoni, Egis Pharmaceuticals PLC, Budapest
Tracy Bale, University of Pennsylvania
Rainer Landgraf, Max Planck Institute of Psychiatry, Munich
Gareth Leng, University of Edinburgh
Stafford Lightman, University of Bristol
Andrew Loudon, University of Manchester
International Neuroendocrine Federation – www.isneuro.org
L'appétit vient en mangeant. Plus on a, plus on veut avoir.
(Appetite comes with eating. The more one has, the more one wants to have.)
When we reflect over this French saying, we realize the complexity of this term ‘appetite.’ It describes an instinctive need to eat that extends beyond the metabolic need for the calories, macronutrients, and micronutrients found in foods to encompass the pure pleasure of eating. This hedonic component to appetite undoubtedly contributes to the tendency to over-consume when palatable foods are available. From an evolutionary perspective, appetite is important for survival, ensuring that we went out into our environment to seek out and eat foods, including foods of diverse nutritional value, and that we maximized the energetic and nutritional gain during this previously ‘risky’ undertaking. The neuroendocrinology of appetite involves extensive neurobiological pathways, distributed throughout the brain, including those that sense energy need, that process hunger and satiety information being forwarded from the gastrointestinal tract and peripheral tissues, that predict the energy and reward value of foods, as well as those that generate a behavioral outcome that culminates in a feeding response.
In the 1950s, classic lesion and stimulation experiments identified regions in the hypothalamus that were important for energy balance, including the lateral hypothalamus that was designated a role in hunger, and the ventromedial nucleus with a role in satiation. Although advances over subsequent decades revealed that this rather simplified push–pull model concealed a complex network of interconnected nuclei in the hypothalamus and beyond, it formed the foundation of a growing research field. This field was enormously invigorated by the discovery of leptin in 1994 by the group of Jeffrey Friedman, a seminal finding that opened a window on brain function for energy balance control, and enabled the identification of specific pathways that direct food intake and associated behaviors, as well as those involved in energy expenditure. In this volume, we provide a state-of-the-art account of these and other hypothalamic regions of importance for appetite, including the key orexigenic and anorexigenic pathways and their ontogeny and electrophysiological properties. We describe the many afferent signaling systems, including the prominent role of gut-derived circulating appetite-regulating hormones, such as ghrelin and glucagon-like peptide-1. These hormones engage hypothalamic pathways but also afferent pathways in the brainstem and higher brain areas involved in reward-based eating and craving behaviors. We introduce the reader to behavioral models commonly used to study feeding control in pre-clinical research including reward-based feeding as well as transgenic and knockout technologies and how these are being used to advance knowledge in the field. Major advances have also been made through the introduction of optogenetics, a technology in which the activity of a specific target cell group is controlled by the activation of light-sensitive channels. Advances in human brain imaging have shown the translational value of much of this work originating in rodents and we introduce the reader to cutting edge technologies in this field also.
We can also learn about the neuroendocrinology of appetite through understanding pathophysiological process that lead to dysregulated eating behaviors. We explore animal models of anorexia and binge eating for which the normal physiological processes controlling appetite break down or are over-ridden. Loss of feeding control, both what we eat and how much we eat, is also a feature of common obesity. Here we have lessons to learn from the field of bariatric (weight loss) surgery in which rearrangement of the gastrointestinal tract can lead to an almost miraculous recovery of dietary control, with healthier dietary selections, and rapid reversal of metabolic complications. We review knowledge of the potential mechanisms involved, including the impact on gut hormone secretion and appetitive brain networks. Finally, progress in appetite control will require effective pharmacotherapies, not only for weight loss but also for the maintenance of a lower body weight in the postobese state. Many such drugs have reached clinical development, but equally many have fallen by the wayside either during development or after introduction onto the market. We discuss some of the recent progress in this area and the obstacles that face those at the front line of therapeutic development.
Suzanne L. Dickson, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Julian G. Mercer, The Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK