Appetite and Body Weight -

Appetite and Body Weight (eBook)

Integrative Systems and the Development of Anti-Obesity Drugs
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2011 | 1. Auflage
384 Seiten
Elsevier Science (Verlag)
978-0-08-046646-0 (ISBN)
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There is now enough basic work to sketch out the principal systems at all levels of the brain, from prefrontal cortex to lower brainstem, which are orchestrated to provide control of food selection, preference and consumption. At the same time, the complex interplay between central systems and signals generated from peripheral systems include the gut, liver and fat stores, as well as the interactions with the neuroendocrine system can be described in some detail. A continuing theme throughout the book is that the functional analysis of appetite and food intake cannot be limited to a single focus, e.g. hypothalamic neuropeptides and their interactions, but must be based on a fully integrated view of the several contributing systems.

Appetite and Body Weight: Integrative Systems and the Development of Anti-Obesity Drugs provides an expert guide to the neural, neurochemical, autonomic and endocrine interrelations which underpin appetite and the controls of food intake and body weight. The book covers many of the neurochemical entities that are currently under investigation, including: neuropeptides, leptin, insulin, monoamines and endogenous cannabinoids in relation to appetite and body-weight control. In addition to the neuroscience analysis, there are also chapters that provide an expert guide to some of the key psychological concepts that the researchers believe are essential in trying to understand the phenomena under investigation. The volume will also serve as an authoritative guide to the current emphasis on the development of novel, efficacious anti-obesity medication.

* Provides an integrative view of the many systems involved in appetite and how they interact to effect food intake (i.e. the brain, endocrine, gut, liver etc.)
* Considers psychological aspects such as incentive, preference, liking and palatability, and sets these concepts in their behavioural, pharmacological and neural contexts
* Examines the development of novel anti-obesity drugs, drawing on experience of pharmacological development work, pre-clinical tests for anti-obesity efficacy, and clinical trials of candidate anti-obesity compounds
There is now enough basic work to sketch out the principal systems at all levels of the brain, from prefrontal cortex to lower brainstem, which are orchestrated to provide control of food selection, preference and consumption. At the same time, the complex interplay between central systems and signals generated from peripheral systems include the gut, liver and fat stores, as well as the interactions with the neuroendocrine system can be described in some detail. A continuing theme throughout the book is that the functional analysis of appetite and food intake cannot be limited to a single focus, e.g. hypothalamic neuropeptides and their interactions, but must be based on a fully integrated view of the several contributing systems. Appetite and Body Weight: Integrative Systems and the Development of Anti-Obesity Drugs provides an expert guide to the neural, neurochemical, autonomic and endocrine interrelations which underpin appetite and the controls of food intake and body weight. The book covers many of the neurochemical entities that are currently under investigation, including: neuropeptides, leptin, insulin, monoamines and endogenous cannabinoids in relation to appetite and body-weight control. In addition to the neuroscience analysis, there are also chapters that provide an expert guide to some of the key psychological concepts that the researchers believe are essential in trying to understand the phenomena under investigation. The volume will also serve as an authoritative guide to the current emphasis on the development of novel, efficacious anti-obesity medication. Provides an integrative view of the many systems involved in appetite how they interact to effect food intake (i.e. the brain, endocrine, gut, liver etc.) Considers psychological aspects such as incentive, preference, liking and palatability, and sets these concepts in their behavioural, pharmacological and neural contexts Examines the development of novel anti-obesity drugs, drawing on experience of pharmacological development work, pre-clinical tests for anti-obesity efficacy, and clinical trials of candidate anti-obesity compounds

Front cover 1
APPETITE AND BODY WEIGHT 4
Copyright page 5
Table of Contents 6
Contributors 10
CHAPTER 1: Introduction and Overview 12
CHAPTER 2: Cortical Systems Involved in Appetite and Food Consumption 16
I. INTRODUCTION 16
II. FOOD MOTIVATION 17
III. CORTICAL REPRESENTATIONS OF SENSORY INPUTS 19
IV. CONCLUSION 31
Acknowledgments 33
References 33
CHAPTER 3: The Nucleus Accumbens Shell as a Model of Integrative Subcortical Forebrain Systems Regulating Food Intake 38
I. INTRODUCTION 39
II. THE REGULATION OF FEEDING BEHAVIOR BY THE NUCLEUS ACCUMBENS SHELL 40
III. AFFERENT PROJECTIONS TO THE AcbSh THAT MAY BE INVOLVED IN REGULATING FOOD INTAKE 49
IV. DOWNSTREAM COMPONENTS OF THE FUNCTIONAL AcbSh FEEDING CIRCUIT 54
V. THE AcbSh FEEDING CIRCUIT AS A POTENTIAL SITE FOR PATHOLOGY AND THERAPEUTIC INTERVENTION IN THE TREATMENT OF EATING DISORDERS 64
References 66
CHAPTER 4: Hypothalamic Neuropeptides and Feeding Regulation 78
I. INTRODUCTION 79
II. NEUROPEPTIDE Y 80
III. THE OREXINS 86
IV. MELANIN-CONCENTRATING HORMONE 89
V. CONCLUSION 92
Acknowledgments 92
References 92
CHAPTER 5: Brainstem-Hypothalamic Neuropeptides and the Regulation of Feeding 110
I. THE CONTROL OF FEEDING 111
II. NEURAL INTEGRATION BY THE DORSAL VAGAL COMPLEX 114
III. CONSIDERATIONS IN ASSESSING THE ROLE OF “NEUROPEPTIDES” 116
IV. “HUMORAL” INTERACTIONS WITH THE DORSAL VAGAL COMPLEX 118
V. INTRINSIC PEPTIDERGIC NEURONS OF THE DORSAL VAGAL COMPLEX 125
VI. DESCENDING PEPTIDERGIC REGULATION OF BRAINSTEM FEEDING CIRCUITS 130
VII. SUMMARY AND POTENTIAL FOR DRUG DEVELOPMENT 133
References 134
CHAPTER 6: The Gut–Brain Axis in the Control of Eating 154
I. INTRODUCTION 155
II. GASTRIC MECHANORECEPTION 156
III. INTESTINAL CHOLECYSTOKININ (CCK) 157
IV. AMYLIN 163
V. GHRELIN 166
VI. POTENTIALS AND PROBLEMS OF GUT–BRAIN AXIS SIGNALS IN THE TREATMENT OF OBESITY 169
References 171
CHAPTER 7: Integration of Peripheral Adiposity Signals and Psychological Controls of Appetite 178
I. INTRODUCTION AND OVERVIEW 179
II. MESOLIMBIC DOPAMINE CIRCUITRY AND ENERGY REGULATORY SIGNALS 181
III. BRAIN OPIOID SYSTEMS AND ENERGY REGULATORY SIGNALS 182
IV. ENDOCANNABINOIDS AND ENERGY REGULATORY SIGNALS 186
V. LHA CIRCUITRY AND ENERGY REGULATORY SIGNALS 187
VI. OTHER CNS SITES: TARGET FOR FUTURE STUDIES? 189
VII. HUMAN AND CLINICAL STUDIES: AT THE FOREFRONT OF OUR KNOWLEDGE 190
VIII. CONCLUDING REMARKS 194
Acknowledgments 194
References 194
CHAPTER 8: Brain Reward Systems for Food Incentives and Hedonics in Normal Appetite and Eating Disorders 202
I. INTRODUCTION 203
II. POSSIBLE ROLES OF BRAIN REWARD SYSTEMS IN EATING DISORDERS 203
III. UNDERSTANDING BRAIN REWARD SYSTEMS FOR FOOD “LIKING” AND “WANTING” 204
IV. “WANTING” WITHOUT “LIKING” 212
V. A BRIEF HISTORY OF APPETITE: FOOD INCENTIVES, NOT HUNGER DRIVES 219
VI. CONNECTING BRAIN REWARD AND REGULATORY SYSTEMS 221
VII. CONCLUSION 221
Acknowledgments 222
References 222
CHAPTER 9: Pharmacology of Food, Taste, and Learned Flavor Preferences 228
I. INTRODUCTION 228
II. PHARMACOLOGY OF FOOD PREFERENCE 230
III. PHARMACOLOGY OF UNLEARNED TASTE PREFERENCE AND REACTIVITY 235
IV. PHARMACOLOGY OF LEARNED FLAVOR PREFERENCE 243
V. CONCLUDING REMARKS 247
Acknowledgments 249
References 249
CHAPTER 10: The Role of Palatability in Control of Human Appetite: Implications for Understanding and Treating Obesity 258
I. INTRODUCTION 259
II. ASSESSING THE EFFECTS OF PALATABILITY ON APPETITE 259
III. PALATABILITY AND THE CONTROL OF NORMAL APPETITE 261
IV. PALATABILITY AND OBESITY 273
V. CONCLUSION 275
References 275
CHAPTER 11: Learned Influences on Appetite, Food Choice, and Intake: Evidence in Human Beings 282
I. INTRODUCTION 283
II. INNATE INFLUENCES ON HUMAN EATING 284
III. TYPES OF LEARNING 285
IV. THE LEARNED APPETITE FOR ENERGY 288
V. LEARNED MODULATION OF APPETITE AND MEAL SIZE BY ASSOCIATED STATES 289
VI. NUTRIENT-SPECIFIC LEARNED APPETITES 294
VII. FLAVOR-FLAVOR LEARNING 297
VIII. AWARENESS AND DIETARY LEARNING 301
IX. SUMMARY 304
References 305
CHAPTER 12: Gene Environment Interactions and the Origin of the Modern Obesity Epidemic: A Novel “Nonadaptive Drift” Scenario 312
I. INTRODUCTION 313
II. EVIDENCE SUPPORTING THE FAMINE HYPOTHESIS 314
III. EVIDENCE AGAINST THE FAMINE HYPOTHESIS 315
IV. THE CHALLENGE FACING EVOLUTIONARY SCENARIOS FOR THE GENETIC PREDISPOSITION TO OBESITY IN MODERN SOCIETIES 317
V. AN ALTERNATIVE MODEL FOR THE EVOLUTION OF THE GENETIC BASIS FOR OBESITY 317
VI. TIME TRENDS IN OBESITY PREVALENCE: THE INTERACTION OF PHYSIOLOGY AND SOCIAL FACTORS 325
VII. IMPLICATIONS 327
Acknowledgments 329
References 329
CHAPTER 13: Preclinical Developments in Antiobesity Drugs 334
I. INTRODUCTION 335
II. CNS TARGETS FOR NOVEL ANTIOBESITY DRUGS 336
III. PERIPHERAL TARGETS FOR NOVEL ANTIOBESITY DRUGS 341
IV. CONCLUSION 343
References 344
CHAPTER 14: Clinical Investigations of Antiobesity Drugs 348
I. INTRODUCTION 349
II. A BRIEF HISTORY OF OBESITY PHARMACOTHERAPY 349
III. CURRENTLY AVAILABLE DRUGS LICENSED FOR OBESITY TREATMENT 350
IV. POTENTIAL NEW TARGETS FOR OBESITY DRUG DEVELOPMENT 353
V. PRECLINICAL TESTING 356
VI. REGULATORY REQUIREMENTS FOR CLINICAL DEVELOPMENT 357
References 363
Index 368
Color Plates 384

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