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Abdominal Obesity and the Endocannabinoid System - J. Despres, V. Di Marzo (Informa, 2009) WW PDF

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Template_7x10_Hamilton.indd about the book… This internationally renowned author team provides a unique and thorough analysis and distillation of the endocannabinoid system and its relationship to abdominal obesity, diabetes, and cardiovascular disease. The endocannabinoid system (ECS) plays an important role in cardiometabolic risk, as well as modulating energy balance, feeding behavior, hepatic lipogenesis, and perhaps glucose homeostasis. Evidence suggests that the ECS is overactive in human obesity and dyslipidemia. Critical to the management of cardiometabolic risk, this new, timely book provides practical overviews and management guidance on many important topics, including: • abdominal obesity and the metabolic syndrome • the endocannabinoid system and energy balance: functions and dysfunctions • abdominal obesity, the EC system, and cardiometabolic risk about the editors... JEAN-PIERRE DESPRÉS is Professor at the Division of Kinesiology of the Department of Social and Preventive Medicine at Université Laval, Québec, Canada. He received his Ph.D. in Exercise Physiology from Université Laval and then pursued a post-doctoral training at the Department of Medicine of the University of Toronto. Dr. Després is Director of Research at the Québec Heart Institute in Québec City and holds the position of Scientific Director of the International Chair on Cardiometabolic Risk, a multi-disciplinary academic organisation based at Université Laval. Dr. Després has been the Editor for the International Journal of Obesity from 1992 to 2000, and he is currently a member of the editorial boards of several scientific journals He also serves on the board of numerous organisation and has been the recipient of many awards. Dr. Després has published more than 480 papers in peer-reviewed journals and has written 50 book chapters. VINCENZO DI MARZO is Research Director at the Istituto di Chimica Biomolecolare, Pozzuoli (Naples), Italy, and Adjunct Associate Professor at Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA. Dr. Di Marzo received his first degree in chemistry from the University of Naples “Federico II”, in Italy, and his Ph.D. in biochemistry from the Imperial College of Science. Technology & Medicine, London, UK. Among his many achievements, Dr. Di Marzo was the principal investigator of a Human Frontier in Science Organization grant and past president of the International Cannabinoid Research Society, and founded the Endocannabinoid Research Group, in which several laboratories working on endocannabinoids in the Naples area converge. He has co- authored over 340 articles in peer-reviewed scientific journals. In 2007 he received the Mechoulam Award for “his outstanding contributions to cannabinoid research”. Printed in the United States of America H6084 Endocrinology nC nM nY nK Abdominal Obesity and the Endocannabinoid System From Basic Aspects to Clinical Management of Related Cardiometabolic Risk Després • Di Marzo From Basic Aspects to Clinical Management of Related Cardiometabolic Risk Abdominal Obesity and the Endocannabinoid System Edited by Jean-Pierre Després and Vincenzo Di Marzo Despres_978-1420060843.indd 1 10/31/08 12:51:02 PM Abdominal Obesity and the Endocannabinoid System Despres_978-1420060843_TP.indd 1 10/31/08 12:51:26 PM Edited by Jean-Pierre Després Université Laval Quebec, Canada Vincenzo Di Marzo Consiglio Nazionale delle Ricerche Pozzuoli, Napoli, Italy From Basic Aspects to Clinical Management of Related Cardiometabolic Risk Abdominal Obesity and the Endocannabinoid System Despres_978-1420060843_TP.indd 2 10/31/08 12:51:26 PM SJT SJT IHBK010-FM IHBK010-Despress October 29, 2008 20:30 Char Count= Informa Healthcare USA, Inc. 52 Vanderbilt Avenue New York, NY 10017 C⃝ 2009 by Informa Healthcare USA, Inc. Informa Healthcare is an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number ISBN-13: 978-1-4200-6084-3 International Standard Book Number ISBN-10: 1-4200-6084-8 This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequence of their use. No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Abdominal obesity and the endocannabinoid system : from basic aspects to clinical management of related cardiometabolic risk / edited by Jean-Pierre Despres,Vincenzo Di Marzo. p. ; cm. Includes bibliographical references and index. ISBN-13: 978-1-4200-6084-3 (hardcover : alk. paper) ISBN-10: 1-4200-6084-8 (hardcover : alk. paper) 1. Obesity–Molecular aspects. 2. Abdomen. 3. Cannabinoids. I. Despr´es, Jean-Pierre. II. Di Marzo, Vincenzo. [DNLM: 1. Obesity–complications. 2. Abdominal Fat. 3. Cardiovascular Diseases. 4. Endocannabinoids–physiology. 5. Metabolic Syndrome X. WD 210 A1355 2008] RC628.A233 2008 362.196’398–dc22 2008042736 For Corporate Sales and Reprint Permissions call 212–520-2700 or write to: Sales Department, 52 Vanderbilt Avenue, 16th floor, New York, NY 10017. Visit the Informa Web site at www.informa.com and the Informa Healthcare Web site at www.informahealthcare.com SJT SJT IHBK010-FM IHBK010-Despress November 11, 2008 18:2 Char Count= Foreword The worldwide development of an obesity epidemic with associated diabetes and cardiovas- cular disease represents one of the major challenges of the 21st century. Both the biomedical research investigator as well as the clinician are being challenged to advance our present under- standing of the etiology and pathophysiology of obesity as well as to develop new therapeutic approaches to control the epidemic. During the last several years major new insights have been made in our understanding of the clinical importance of the adipocyte. The role of the adipocyte has evolved from that of an uninteresting storage organ for lipids to that of a dynamic endocrine organ which secretes hormones and cytokines which play a pivotal role in regulating metabolism, inflammation, and cardiovascular disease. Of particular importance has been the realization that there are marked differences in the metabolism of visceral and peripheral adi- posity. Current evidence indicates that visceral obesity accompanied by ectopic fat in the liver and muscle is associated with insulin resistance and an increased risk of the development of dia- betes and vascular disease. The frequent combination of visceral obesity and insulin resistance with increased triglycerides, low HDL, increased blood pressure and elevated blood glucose has led to the codification of this multiplex risk factor as the insulin resistance syndrome or metabolic syndrome. Although the academic community has struggled with the selection of the most effective nosology to deal with this constellation of risk factors, the underlying evidence that patients with the metabolic syndrome are at risk for the future development of diabetes and cardiovascular events continues to accrue. The addition of risk factors associated with the metabolic syndrome to the classical risk factors for cardiovascular disease has resulted in the concept of global cardiometabolic risk. The ultimate clarification of whether the metabolic risk factors associated with visceral adiposity and ectopic fat will predict cardiovascular events beyond or independently from the classical risk factors awaits further clinical studies. An addi- tional advancement in the clinical assessment of high risk patients will be the delineation of individual risk factors as a continuum of severity rather than a dichotomized classification system. For the practicing physician a clinical clue for the identification of the high risk obese patient with insulin resistance and the metabolic syndrome from the low risk equally obese individual is an increased waist circumference and elevated triglycerides. A major breakthrough in our understanding of the pathophysiological basis of obesity and the metabolic syndrome has been the elucidation of the role of the endocannabinoid system in the regulation of caloric intake and metabolism. The identification of the CB1 receptor and the metabolic effects of regulation of the endocannabinoid pathways in the brain as well as peripheral organs have provided major new insights into lipid and glucose metabolism as well as obesity. Although a definitive understanding of the endocannabinoid system is being actively pursued in laboratories around the world, the ability to modulate a potentially dysfunctional endocannabinoid system in obesity and the metabolic syndrome has arrived. Clinical experience with CB1 antagonists, in conjunction with aggressive lifestyle changes, is currently underway and the evaluation of side effects as well as the selection of the appropriate patient for treatment will be ascertained. The chapters in this book provide an up to date unique compendium of basic research and clinical information from investigators with expertise in both obesity and the endocannabi- noid system. A comprehensive analysis of the topics presented in the individual chapters will provide the reader with an exceptional in-depth knowledge of this exciting and explosive area of medicine Bryan Brewer, Jr. Cardiovascular Research Institute Washington Hospital Center Washington, D.C., U.S.A. SJT SJT IHBK010-FM IHBK010-Despress November 11, 2008 18:51 Char Count= Preface Why a book on abdominal obesity and the endocannabinoid system? This work summarizes about 20 years of exciting developments and conceptual advances in our understanding of the form of overweight/obesity carrying the highest risk for chronic disease: visceral obesity. Indeed, we now better understand that many complications of obesity are more related to the distribution of body fat than to excess total fat per se. On the other hand, studies conducted over the last decade have documented the importance of the endocannabinoid system in the control of regional fat deposition and in the regulation of carbohydrate and lipid metabolism. Thus, it is only recently that we have begun to recognize the interplay between a dysfunc- tional endocannabinoid system and visceral obesity and its complications. These notions have tremendously important clinical implications on how to target the endocannabinoid system in order to reduce abdominal obesity. Unfortunately, the pharmaceutical industry and regulatory agencies have used the old “overall obesity” paradigm to evaluate “anti-obesity” drugs under development, including the antagonists of endocannabinoid action. This traditional view of obesity, assessed in the old fashioned way on the basis of indices of relative weight such as the body mass index, have led to a very difficult and uncertain path for drug developers and for physicians and their patients who are still expecting a “miracle drug”. This book is currently the most comprehensive effort at describing the endocannabinoid system as a whole and its role in the regulation of body fat distribution and of abdominal obesity-related metabolic complications that increase the risk of type 2 diabetes and cardiovas- cular disease. Whether pharmaceutical companies and regulatory bodies will agree on better experimental designs and more carefully selected patient populations for the evaluation of drugs targeting the endocannabinoid system is, at this stage, unclear. We hope that this comprehensive effort will help shed light on these issues. Jean-Pierre Despr´es Vincenzo Di Marzo SJT SJT IHBK010-FM IHBK010-Despress November 11, 2008 19:30 Char Count= Contents Foreword Bryan Brewer, Jr. . . . . iii Preface . . . . iv Contributors . . . . ix 1. Abdominal Obesity, Metabolic Syndrome, and Risk of Cardiovascular Disease 1 Jean-Pierre Despr´es and Vincenzo Di Marzo 2. Abdominal Obesity in Type 2 Diabetes 11 Isabelle Lemieux and Jean-Pierre Despr´es 3. Obesity and Hypertension 19 Paul Poirier and Caroline Rh´eaume 4. Visceral Adiposity, Liver Fat, and Atherogenic Dyslipidemia 27 Marja-Riitta Taskinen, Martin Adiels, and Jan Bor´en 5. Visceral Adiposity and Inflammation 33 Ulf Smith 6. Abdominal Obesity and Alterations in Haemostasis—Thrombosis 37 Ir`ene Juhan-Vague and Marie-Christine Alessi 7. Physiological and Metabolic Characteristics of Visceral Adipocytes 49 Alain Veilleux and Andr´e Tchernof 8. The Endocrine Function of Adipose Tissue: Implications of Visceral Obesity for Patients With Cardiometabolic Risk 55 Max Lafontan 9. Free Fatty Acid Metabolism in Visceral Obesity 69 Asem Ali and Michael D. Jensen 10. Animal Models of Visceral Obesity 75 Derek M. Huffman and Nir Barzilai 11. Insulin Sensitivity and Visceral Adiposity: Effects of Rimonabant 81 Joyce M. Richey, Morvarid Kabir, Orison O. Woolcott, Stella P. Kim, Lisa N. Harrison, Darko Stefanovski, Isabel Hsu, Dan Zheng, Maya Lottati, Cathryn Kolka, Viorica Ionut, Karyn Catalano, Jenny D. Chiu, and Richard N. Bergman 12. Physical Activity in the Management of Visceral Obesity and Related Cardiometabolic Risk 89 Peter M. Janiszewski and Robert Ross 13. Can We Change the Lifestyle of High-Risk Patients? Lessons from the Prevention of Diabetes Trials 105 Jaakko Tuomilehto and Jaana Lindstr¨om SJT SJT IHBK010-FM IHBK010-Despress October 24, 2008 20:18 Char Count= vi Contents 14. Can We Change the Body Fat Distribution Phenotype? Lessons from PPAR� Agonists 111 Zubin Punthakee and Hertzel C. Gerstein 15. Is There an Optimal Diet for the Management of Abdominal Obesity and Related Cardiometabolic Risk 117 Benoˆıt Lamarche and Caroline Richard 16. The EC System and Central Control of Energy Balance—The Hypothalamus 123 Vincenzo Di Marzo 17. The EC System and Central Control of Energy Balance: The Nucleus Accumbens 129 Tim C. Kirkham 18. The EC System and the HPA Axis 137 Daniela Cota 19. The EC System and Gut–Brain Interactions Relevant to Satiety 141 Richard Jones, Galina Burdyga, David G. Thompson, and Graham J. Dockray 20. The Endogenous Cannabinoid System in the Gastrointestinal Tract 147 Angelo A. Izzo 21. The EC System in the Adipose Tissue and Endocrine Pancreas 153 Isabel Matias 22. The EC System in the Immune System and the Inflammatory Response 163 Tracy A. Sherwood and Thomas W. Klein 23. The Endocannabinoid System in the Liver 173 Ariane Mallat and Sophie Lotersztajn 24. The Endocannabinoid System and Cardiovascular Disease 179 P´al Pacher and George Kunos 25. The Endocannabinoid System, Energy Expenditure, and Thermogenesis 185 Luigi Bellocchio, Cristina Cervino, Valentina Vicennati, Renato Pasquali, and Uberto Pagotto 26. Effects of Dietary Fatty Acids on Endocannabinoid Signaling in the Brain and Peripheral Organs 191 Alvin Berger and Vincenzo Di Marzo 27. Endocannabinoid Overactivity and Abdominal Obesity 203 Vincenzo Di Marzo and Jean-Pierre Despr´es 28. CB1 Antagonism in the Management of Abdominal Obesity 209 Luc F. Van Gaal 29. Abdominal Obesity and the Endocannabinoid System CB1 Blockade, Insulin Resistance, and Type 2 Diabetes 219 Andr´e J. Scheen 30. Abdominal Obesity As a Therapeutic Target to Manage the Atherogenic Dyslipidemia and Related Metabolic Abnormalities 227 Jean-Pierre Despr´es 31. CB1 Blockade and Hypertension 237 Luis M. Ruilope SJT SJT IHBK010-FM IHBK010-Despress October 24, 2008 20:18 Char Count= Contents vii 32. Future Developments 1: CB1 Blockade for Weight Gain Subsequent to Smoking Cessation 247 Jaimee L. Heffner and Robert M. Anthenelli 33. Future Developments 2: Cannabinoid CB1 Receptor Blockade in Weight Gain Subsequent to Psychiatric Disorder Treatment 253 Ester Fride, Shimon Rabichev, and Nikolai Gobshtis Index . . . . 261

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