Appetite and Body Weight: Integrative Systems and the Development of Anti-Obesity Drugs

379 Pages·2006·9.22 MB·English

by  Tim Kirkham

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APPETITE AND
BODY WEIGHT
integrative systems and the development
of anti-obesity drugs
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APPETITE AND
BODY WEIGHT
Integrative Systems and the
Development of Anti-Obesity Drugs
Edited by
TIM C. KIRKHAM
and
STEVEN J. COOPER
University of Liverpool, School of Psychology, Liverpool, UK
AMSTERDAM• BOSTON• HEIDELBERG• LONDON
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Contents
Contributors vii
1. Introduction and Overview 1
Steven J. Cooper and Tim C. Kirkham
2. Cortical Systems Involved in Appetite and Food Consumption 5
Morten L. Kringelbach
I. Introduction 5
II. Food Motivation 6
III. Cortical Representations of Sensory Inputs 8
IV. Conclusion 20
Acknowledgments 20
References 20
3. The Nucleus Accumbens Shell as a Model of Integrative Subcortical Forebrain Systems
Regulating Food Intake 27
Thomas R. Stratford
I. Introduction 28
II. The Regulation of Feeding Behavior by the Nucleus Accumbens Shell 29
III. Afferent Projections to the AcbSh That May Be Involved in Regulating Food Intake 38
IV. Downstream Components of the Functional AcbSh Feeding Circuit 43
V. The AcbSh Feeding Circuit As a Potential Site for Pathology and Therapeutic
Intervention in the Treatment of Eating Disorders 53
References 55
4. Hypothalamic Neuropeptides and Feeding Regulation 67
Bernard Beck
I. Introduction 68
II. Neuropeptide Y 69
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CONTENTS
III. The Orexins 75
IV. Melanin-Concentrating Hormone 78
V. Conclusion 81
Acknowledgments 81
References 81
5. Brainstem-Hypothalamic Neuropeptides and the Regulation of Feeding 99
Simon M. Luckman
I. The Control of Feeding 100
II. Neural Integration by the Dorsal Vagal Complex 103
III. Considerations in Assessing the Role of “Neuropeptides” 105
IV. “Humoral” Interactions with the Dorsal Vagal Complex 107
V. Intrinsic Peptidergic Neurons of the Dorsal Vagal Complex 114
VI. Descending Peptidergic Regulation of Brainstem Feeding Circuits 119
VII. Summary and Potential for Drug Development 122
References 123
6. The Gut-Brain Axis in the Control of Eating 143
Thomas A. Lutz and Nori Geary
I. Introduction 144
II. Gastric Mechanoreception 145
III. Intestinal Cholecystokinin (CCK) 146
IV. Amylin 152
V. Ghrelin 155
VI. Potentials and Problems of Gut–Brain Axis Signals in the Treatment of Obesity 158
References 160
7. Integration of Peripheral Adiposity Signals and Psychological Controls of Appetite 167
Dianne Figlewicz Lattemann, Nicole M. Sanders, Amy MacDonald Naleid and Alfred J. Sipols
I. Introduction and Overview 168
II. Mesolimbic Dopamine Circuitry and Energy Regulatory Signals 170
III. Brain Opioid Systems and Energy Regulatory Signals 171
IV. Endocannabinoids and Energy Regulatory Signals 175
V. LHA Circuitry and Energy Regulatory Signals 176
VI. Other CNS Sites: Target for Future Studies? 178
VII. Human and Clinical Studies: At the Forefront of Our Knowledge 179
VIII. Concluding Remarks 183
Acknowledgments 183
References 183
8. Brain Reward Systems for Food Incentives and Hedonics in Normal Appetite and Eating
Disorders 191
Kent C. Berridge
I. Introduction 192
II. Possible Roles of Brain Reward Systems in Eating Disorders 192
III. Understanding Brain Reward Systems for Food “Liking” and “Wanting” 193
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CONTENTS
IV. “Wanting” Without “Liking” 201
V. A Brief History of Appetite: Food Incentives, Not Hunger Drives 208
VI. Connecting Brain Reward and Regulatory Systems 210
VII. Conclusion 210
Acknowledgments 211
References 211
9. Pharmacology of Food, Taste and Learned Flavor Preferences 217
Steven J. Cooper
I. Introduction 217
II. Pharmacology of Food Preference 219
III. Pharmacology of Unlearned Taste Preference and Reactivity 224
IV. Pharmacology of Learned Flavor Preference 232
V. Concluding Remarks 236
Acknowledgments 238
References 238
10. The Role of Palatability in Control of Human Appetite: Implications for Understanding
and Treating Obesity 247
Martin R. Yeomans
I. Introduction 248
II. Assessing the Effects of Palatability on Appetite 248
III. Palatability and the Control of Normal Appetite 250
IV. Palatability and Obesity 262
V. Conclusion 264
References 264
11. Learned Influences on Appetite, Food Choice, and Intake: Evidence in Human
Beings 271
E.L. Gibson and J.M. Brunstrom
I. Introduction 272
II. Innate Influences on Human Eating 273
III. Types of Learning 274
IV. The Learned Appetite for Energy 277
V. Learned Modulation of Appetite and Meal Size by Associated States 278
VI. Nutrient-Specific Learned Appetites 283
VII. Flavor-Flavor Learning 286
VIII. Awareness and Dietary Learning 290
IX. Summary 293
References 294
12. Gene Environment Interactions and the Origin of the Modern Obesity Epidemic:
A Novel “Nonadaptive Drift” Scenario 301
John R. Speakman
I. Introduction 302
II. Evidence Supporting the Famine Hypothesis 303
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CONTENTS
III. Evidence Against the Famine Hypothesis 304
IV. The Challenge Facing Evolutionary Scenarios for the Genetic Predisposition to
Obesity in Modern Societies 306
V. An Alternative Model for the Evolution of the Genetic Basis for Obesity 306
VI. Time Trends in Obesity Prevalence: The Interaction of Physiology and Social
Factors 314
VII. Implications 316
Acknowledgments 318
References 318
13. Preclinical Developments in Antiobesity Drugs 323
Steven P. Vickers and Sharon C. Cheetham
I. Introduction 324
II. CNS Targets for Novel Antiobesity Drugs 325
III. Peripheral Targets for Novel Antiobesity Drugs 330
IV. Conclusion 332
References 333
14. Clinical Investigations of Antiobesity Drugs 337
John Wilding
I. Introduction 338
II. A Brief History of Obesity Pharmacotherapy 338
III. Currently Available Drugs Licensed for Obesity Treatment 339
IV. Potential New Targets for Obesity Drug Development 342
V. Preclinical Testing 345
VI. Regulatory Requirements for Clinical Development 346
References 352
Index 357
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Contributors
Numbers in parenthesis indicate the chapter to which the author has contributed
Bernard Beck(4) INSERM U.724, Neurocal Group—Faculté de Médecine, B.P. 184—Avenue
de la Forêt de Haye, 54500 vandŒuvre les Nancy, France
Kent C. Berridge (8) The University of Michigan, Department of Psychology (Biopsychol-
ogy Program), 525 E. University, Ann Arbor, MI, 48109, USA
J.M. Brunstrom (11) Bristol University, Department of Experimental Psychology, 8
Woodland Road, Bristol, BS8 1TN, United Kingdom
Sharon C. Cheetham(13) RenaSci Consultancy Ltd, BioCity, Nottingham, Pennyfoot Street,
Nottingham, NG1 1GF, United Kingdom
Steven J. Cooper(1, 9) University of Liverpool, School of Psychology, Liverpool, L69 7ZA,
United Kingdom
Dianne Figlewicz Lattemann (7) VA Puget Sound Health Care System, Metabolism/
Endocrinology (151), 1660 So. Columbian Way, Seattle, WA, 98108, USA
Nori Geary (6) Swiss Federal Institute of Technology Zurich (ETHZ), Institute of Animal
Sciences, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland
E.L. Gibson (11) Roehampton University, Whitelands College, School of Human and Life
Sciences, West Hill, Holybourne Avenue, London, SW15 3SN, United Kingdom
Tim C. Kirkham (1) University of Liverpool, School of Psychology, Liverpool, L69 7ZA,
United Kingdom
Morten L. Kringelbach(2) University of Oxford, Department of Physiology, Anatomy and
Genetics, Parks Road, Oxford, OX1 3PT, United Kingdom
Simon M. Luckman (5) University of Manchester, School of Biological Sciences, Oxford
Road, Manchester, M13 3PT, United Kingdom
Thomas A. Lutz (6) University of Zurich, Vetsuisse Faculty, Institute of Veterinary Physi-
ology, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland
Amy MacDonald Naleid (7) University of Washington, Department of Psychiatry and
Behavioral Sciences, Box 356560, Seattle, WA, 98195-6560, USA
Nicole M. Sanders (7) VAPuget Sound Health Care System, Metabolism/Endocrinology
(151), 1660 So. Columbian Way, Seattle, WA, 98108, USA
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