Lustig Obesity Before Birth

Maternal and prenatal influences on the offspring
1. Auflage 2010
ISBN: 978-1-4419-7034-3
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 30, 414 Seiten

Reihe: Endocrine Updates

This volume will explore the epidemiology and the basic mechanisms of each of these prenatal phenomena, in an attempt to explain the role of the prenatal environment in promoting postnatal weight gain. This information will contribute to resolving the nature-nurture controversy. This information provides guidance to clinical practitioners involved in both prenatal and postnatal care. This volume further stimulates research into underlying mechanisms and prevention and treatment of this phenomenon.

Autoren/Hrsg.

Lustig, Robert H

Inhaltsverzeichnis

1;Preface;6
2;Contents;8
3;Contributors;10
4;1 Obesity: Nature or Nurture;13
4.1;1.1 Introduction;13
4.2;1.2 Definitions;14
4.3;1.3 The Nurture Interpretation;14
4.3.1;1.3.1 Risk Factors for Obesity Ascribable to ''Nurture'';15
4.3.2;1.3.2 Problems with the ''Nurture'' Interpretation;15
4.4;1.4 The Nature Interpretation;17
4.4.1;1.4.1 Risk Factors for Obesity Ascribable to ''Nature'';18
4.4.2;1.4.2 Problems with the ''Nature'' Interpretation;19
4.5;1.5 Toward a More Biochemical Understanding of the Nature Versus Nurture Argument;19
4.6;1.6 Hyperinsulinemia and Leptin Resistance;19
4.6.1;1.6.1 Postnatal Hyperinsulinemia, Leptin Resistance, and Obesity;20
4.6.2;1.6.2 Two Clinical Paradigms Have Shown Improvement in Human Leptin Resistance;20
4.6.2.1;1.6.2.1 Forced Weight Loss;20
4.6.2.2;1.6.2.2 Insulin Suppression;21
4.6.3;1.6.3 Prenatal Hyperinsulinemia, Leptin Resistance, and Risk for Future Obesity;22
4.6.4;1.6.4 Studies of SGA and Future Obesity;22
4.6.5;1.6.5 Studies of LGA and Future Obesity;22
4.6.6;1.6.6 Studies of Prematurity and Future Obesity;23
4.6.7;1.6.7 Animal Models of Hypothalamic Maldevelopment: The Role of Neonatal Leptin;23
4.7;1.7 Stress, Glucocorticoids, and Visceral Adiposity;24
4.7.1;1.7.1 Postnatal Stress, Glucocorticoids, and Visceral Adiposity;25
4.7.2;1.7.2 Prenatal Stress, Glucocorticoid Exposure, and Risk for Future Visceral Adiposity;25
4.7.3;1.7.3 Prenatal Glucocorticoid Exposure in Animal Models;26
4.8;1.8 Conclusions;26
4.9;References;27
5;Part I Genetic Disorders Leading to Obesity;35
5.1;2 The Contribution of Heredity to Clinical Obesity;36
5.1.1;2.1 Introduction;36
5.1.2;2.2 Defining Heredity;36
5.1.3;2.3 Clinical Obesity;37
5.1.4;2.4 The Environment;37
5.1.5;2.5 The Obesogenic Environment and the Rise in Obesity;37
5.1.6;2.6 Why Arent We All Obese;38
5.1.7;2.7 Is Obesity Heritable;38
5.1.8;2.8 Twin Studies;38
5.1.8.1;2.8.1 Types of Twin Studies;40
5.1.8.1.1;2.8.1.1 The Classical Twin Study;40
5.1.8.1.2;2.8.1.2 The Extended Twin Study;40
5.1.8.1.3;2.8.1.3 The Co-twin Control Study;41
5.1.8.1.4;2.8.1.4 The Discordant MZ Twin Study;41
5.1.8.1.5;2.8.1.5 Twins Reared Apart;41
5.1.8.1.6;2.8.1.6 Twin Studies to Distinguish Between Genetic and Environmental Effects;42
5.1.8.2;2.8.2 Twin Studies and Obesity;42
5.1.9;2.9 Genetic Linkage Studies Using DZ Twins;42
5.1.10;2.10 Twin Studies of Obesity-Related Traits;43
5.1.10.1;2.10.1 BMI in Children;43
5.1.10.2;2.10.2 BMI in Adolescents;44
5.1.10.3;2.10.3 BMI in Adults;45
5.1.10.4;2.10.4 Other Anthropometric Measures;46
5.1.10.5;2.10.5 Body Composition;46
5.1.10.6;2.10.6 Eating Behavior;49
5.1.10.6.1;2.10.6.1 Restraint, Emotional Eating, and External Eating;49
5.1.10.6.2;2.10.6.2 Satiety and Food Responsiveness;50
5.1.10.6.3;2.10.6.3 Eating Rate and Eating Styles;50
5.1.10.7;2.10.7 Physical Activity;51
5.1.11;2.11 Adoption Studies;53
5.1.12;2.12 Family-Based Studies;54
5.1.13;2.13 CaseControl Studies and the Missing Heritability Problem;55
5.1.14;2.14 Heredity and Nongenetic Traits in Obesity;56
5.1.15;2.15 Conclusions;57
5.1.16;References;58
5.2;3 Monogenic Disorders Within the Energy Balance Pathway;64
5.2.1;3.1 Introduction;64
5.2.2;3.2 Gene Mutations That Affect the LeptinMelanocortin System;65
5.2.2.1;3.2.1 Melanocortin-4 Receptor (MC4R);65
5.2.2.2;3.2.2 Leptin;68
5.2.2.3;3.2.3 Leptin Receptor (LepR);68
5.2.2.4;3.2.4 Proopiomelanocortin (POMC);69
5.2.2.5;3.2.5 Prohormone Convertase 1/3 (PC1/3);70
5.2.3;3.3 Gene Mutations That Affect Neurodevelopment;71
5.2.3.1;3.3.1 SIM1;71
5.2.3.2;3.3.2 Brain-Derived Neurotrophic Factor (BDNF);72
5.2.3.3;3.3.3 NTRK2;73
5.2.4;3.4 Treatment;73
5.2.5;3.5 Conclusions;75
5.2.6;References;76
5.3;4 Ciliary Syndromes and Obesity;81
5.3.1;4.1 Introduction;81
5.3.2;4.2 Ciliary Function, the Ciliopathies, and Clinical Phenotypes;82
5.3.3;4.3 An Overview of the Primary Vertebrate Cilium;83
5.3.4;4.4 Intraflagellar Transport (IFT);84
5.3.5;4.5 A Role for Cilia in Developmental Signaling;85
5.3.5.1;4.5.1 Cilia and Hedgehog Signaling;85
5.3.5.2;4.5.2 Cilia and Wnt Signaling;86
5.3.6;4.6 A Role for Primary Cilia in Appetite Control;87
5.3.6.1;4.6.1 Leptin Signaling in the Hypothalamus Regulates Body Weight;88
5.3.6.2;4.6.2 A Requirement for IFT in Leptin Signaling;88
5.3.6.3;4.6.3 BBS Proteins and the Control of Leptin Signaling;89
5.3.6.4;4.6.4 Other Roles for BBS Proteins in Neuronal Signaling and Obesity;91
5.3.7;4.7 Cilia and Adipogenesis;92
5.3.8;4.8 The Human Ciliopathies and Obesity;93
5.3.9;4.9 BardetBiedl Syndrome;93
5.3.10;4.10 Alstrm Syndrome;95
5.3.11;4.11 Concluding Remarks;96
5.3.12;References;96
5.4;5 Genome-Wide Association Studies and Human Population Obesity;104
5.4.1;5.1 Introduction;104
5.4.2;5.2 Genome-Wide Association (GWA) Studies;105
5.4.2.1;5.2.1 The International HapMap Project and High-Throughput Genotyping -- The Bedrocks of the Genome-Wide Association Approach;105
5.4.2.2;5.2.2 Two-Stage Design of GWA Studies;106
5.4.2.3;5.2.3 Imputation;107
5.4.2.4;5.2.4 Presentation of Genome-Wide Results;107
5.4.3;5.3 Three Waves of Discoveries;108
5.4.3.1;5.3.1 First Wave -- Discovery of FTO;108
5.4.3.2;5.3.2 Second Wave -- Discovery of MC4R;109
5.4.3.3;5.3.3 Third Wave -- Discovery of Nine New Loci;110
5.4.4;5.4 Impact and Predictive Value of the Established Obesity Loci;111
5.4.5;5.5 Follow-Up and Functional Characterization of the Established Loci;113
5.4.6;5.6 Clinical Applications;114
5.4.7;5.7 Approaches for Identifying More Loci for Obesity Through GWA Studies;115
5.4.7.1;5.7.1 Increased Sample Size;115
5.4.7.2;5.7.2 Studies in Populations of Different Ethnic Backgrounds;115
5.4.7.3;5.7.3 Genome-Wide Association Studies in Children and Adolescents;115
5.4.7.4;5.7.4 Studies on Other Obesity-Related Traits than BMI;116
5.4.7.5;5.7.5 Studies on the Risk of Obesity;116
5.4.7.6;5.7.6 Studies on Intermediary Traits of Obesity;116
5.4.7.7;5.7.7 Studies on Gene--Lifestyle Interaction;117
5.4.7.8;5.7.8 Replication of Variants with Less Stringent Significance Thresholds;117
5.4.7.9;5.7.9 Genome-Wide Association of Copy Number Variants (CNVs);118
5.4.7.10;5.7.10 More Comprehensive Genotyping Chips;118
5.4.8;5.8 Conclusions;119
5.4.9;References;119
6;Part II Epigenetic Changes and the Development of Obesity;122
6.1;6 Known Clinical Epigenetic Disorders with an Obesity Phenotype: PraderWilli Syndrome and the GNAS Locus;123
6.1.1;6.1 Introduction;123
6.1.2;6.2 Genomic Imprinting;124
6.1.3;6.3 Genetic Subtypes and Clinical Differences in PWS;125
6.1.3.1;6.3.1 Genetics;125
6.1.3.2;6.3.2 Deletion Versus Maternal Disomy 15;127
6.1.3.3;6.3.3 Molecular Genetics and Deletion Types in PWS;128
6.1.3.4;6.3.4 Clinical Findings Associated with Type I Versus Type II Deletions;132
6.1.3.5;6.3.5 Expression of Four Genes Between BP1 and BP2 in PWS;134
6.1.4;6.4 PWS with Atypical 15q11q13 Deletions or Translocations and Causative Genes;135
6.1.5;6.5 Gene Expression in PWS;136
6.1.6;6.6 Clinical Stages and Natural History of PWS;137
6.1.7;6.7 Fatness Patterns and Body Composition Measures in PWS;140
6.1.8;6.8 Obesity and Nutritional Management in PWS;142
6.1.9;6.9 GNAS, a Complex and Imprinted Locus ;144
6.1.10;6.10 Albright Hereditary Osteodystrophy (AHO), Pseudohypoparathyroidism (PHP), and Pseudopseudohypoparathyroidism (PPHP);145
6.1.11;6.11 McCuneAlbright Syndrome;146
6.1.12;6.12 Applications to Other Areas of Health and Disease Related to Epigenetics and Obesity;148
6.1.13;References;149
6.2;7 Evidence for Epigenetic Changes as a Cause of Clinical Obesity;154
6.2.1;7.1 Introduction;154
6.2.2;7.2 Developmental Plasticity;155
6.2.3;7.3 Developmental Plasticity and Human Metabolic Disease;156
6.2.4;7.4 Experimental Models;158
6.2.5;7.5 Nutrition in Early Life and Gene Transcription;158
6.2.6;7.6 Epigenetic Mechanisms in Induced Risk of Obesity;162
6.2.6.1;7.6.1 Epigenetic Mechanisms and Gene Regulation;162
6.2.6.2;7.6.2 Evidence for the Involvement of Altered Epigenetic Regulation in Human Cardiometabolic Disease;163
6.2.6.3;7.6.3 Epigenetic Regulation in Animal Models;164
6.2.6.4;7.6.4 Mechanisms for Induced Changes in the Epigenome;165
6.2.6.5;7.6.5 Prevention and Reversal of an Altered Epigenotype and Phenotype;166
6.2.7;7.7 Conclusions;168
6.2.8;References;168
6.3;8 Epigenetic Changes Associated with Intrauterine Growth Retardation and Adipogenesis;174
6.3.1;8.1 Introduction;174
6.3.2;8.2 Chromatin Structure, DNA Methylation, and Gene Expression;175
6.3.2.1;8.2.1 Histone Modifications;175
6.3.2.2;8.2.2 DNA Methylation;175
6.3.2.3;8.2.3 Noncoding RNAs;176
6.3.3;8.3 Epigenetic Regulation of Gene Expression in Intrauterine Growth Retardation;176
6.3.3.1;8.3.1 Chromatin Remodeling in the ß-Cell of IUGR Rats;177
6.3.3.2;8.3.2 Chromatin Remodeling in the Muscle of IUGR Rats;178
6.3.4;8.4 Epigenetics of the Adipocyte;180
6.3.5;8.5 Stages of the Developing Adipocyte: Determination and Differentiation;182
6.3.6;8.6 Experimental Systems for Studying Adipogenesis;182
6.3.7;8.7 Adipogenesis;184
6.3.7.1;8.7.1 CAAT/Enhancer-Binding Proteins (C/EBPs);184
6.3.7.2;8.7.2 PPAR-y -- A Master Regulator of Adipogenesis;185
6.3.8;8.8 Epigenetic Regulation of Adipogenesis;185
6.3.8.1;8.8.1 Epigenetic Regulation of Preadipocyte Determination;185
6.3.8.2;8.8.2 Chromatin Remodeling and C/EBP Transcription Factors;188
6.3.8.3;8.8.3 Epigenetic Regulation of PPAR: The Role of Histone Acetylation;189
6.3.8.4;8.8.4 Histone Methylation in Adipogenesis;190
6.3.8.5;8.8.5 DNA Methylation and Gene Expression;191
6.3.9;8.9 Conclusions;191
6.3.10;References;192
7;Part III Developmental Programming and the Development of Obesity;197
7.1;9 Exposure to Diabetes In Utero, Offspring Growth, and Risk for Obesity;198
7.1.1;9.1 Introduction;198
7.1.2;9.2 Maternal Hyperglycemia and Fetal Growth;200
7.1.3;9.3 Early Life Growth Patterns and Risk for Obesity in Offspring of Diabetic Mothers;200
7.1.4;9.4 Abnormal Glucose Tolerance and T2DM in Offspring of Diabetic Mothers;202
7.1.5;9.5 The Role of Fetal Hyperinsulinemia;203
7.1.6;9.6 Less Conclusive Findings;203
7.1.7;9.7 An Independent Effect of Intrauterine Exposure: Beyond Genetics and Postnatal Environment;204
7.1.8;9.8 The Long-Term Consequences Are Independent of Maternal Diabetes Type;205
7.1.9;9.9 Public Health Consequences;205
7.1.10;9.10 Prevention and Risk Reduction Strategies;206
7.1.11;References;206
7.2;10 Maternal Weight Gain During Pregnancy and Obesity in the Offspring;210
7.2.1;10.1 Introduction;210
7.2.2;10.2 The Physiology of Weight Gain During Pregnancy Among Obese and Non-obese Women;210
7.2.3;10.3 The Institute of Medicine (IOM) Weight Gain Guidelines;212
7.2.4;10.4 Epidemiology and Trends of Pregnancy Weight Gain;212
7.2.5;10.5 Association Between Gestational Weight Gain (GWG) and Childhood Obesity;213
7.2.6;10.6 Optimal Weight Gain for Obese Women an Ongoing Controversy;215
7.2.7;10.7 Interventions to Prevent Excessive Pregnancy Weight Gain;216
7.2.8;10.8 Special Diets for Obese Women During Pregnancy;217
7.2.9;References;218
7.3;11 Intrauterine Growth Restriction, Small for Gestational Age, and Experimental Obesity;220
7.3.1;11.1 Introduction;220
7.3.2;11.2 Programming of Obesity;221
7.3.3;11.3 Effects of the In Utero Environment on Fetal Development;222
7.3.4;11.4 Animal Models;223
7.3.5;11.5 Animal Species;224
7.3.6;11.6 Programming Mechanisms and Results: Appetite and Adipogenesis;225
7.3.7;11.7 Appetite Physiology;226
7.3.8;11.8 Development of Appetite and Satiety Mechanisms;227
7.3.8.1;11.8.1 Role of Leptin;227
7.3.8.1.1;11.8.1.1 Animal Leptin Physiology;227
7.3.8.1.2;11.8.1.2 Human Leptin Physiology;229
7.3.8.1.3;11.8.1.3 Research on Neural Stem Cell Cultures (NSC);229
7.3.8.2;11.8.2 Role of Adipose Tissue;229
7.3.9;11.9 Programming of Adiposity;230
7.3.9.1;11.9.1 Enhanced Adipogenesis and Lipogenesis;230
7.3.9.1.1;11.9.1.1 Research in Primary Adipocyte Cultures;232
7.3.10;11.10 Programmed Obesity: Putative Causative Mechanisms;233
7.3.11;11.11 Therapies and Applications;233
7.3.12;11.12 Conclusions;234
7.3.13;References;235
7.4;12 Experimental Models of Maternal Obesity andINTtie;High-Fat Diet During Pregnancy and Programmed ObesityINTnl; in the Offspring;245
7.4.1;12.1 Introduction;245
7.4.2;12.2 Animal Models to Study the Role of Maternal Diet in Pregnancy on Offspring Health and Disease;246
7.4.3;12.3 Animal Models of Maternal Obesity, Hypercaloric Diet, and High-Fat Feeding;247
7.4.4;12.4 What Is the Stimulus to Developmental Programming Following Maternal Obesity, Hypercaloric Diet, or High-Fat Feeding;248
7.4.4.1;12.4.1 Elucidating the Programming Effects of Maternal Obesity and Fat Feeding;249
7.4.4.2;12.4.2 Programming Effects of Maternal Diets Differing in Types of Fatty Acids;250
7.4.4.3;12.4.3 The Relative Importance of Maternal Obesity vs. Maternal Fat Intake in Pregnancy;251
7.4.4.4;12.4.4 The Effect of Maternal Hypercholesterolemia in Developmental Programming;252
7.4.5;12.5 The Postnatal Period Is Important and Implicates a Role for Altered Appetite Circuitry in the Development of Programmed Obesity;253
7.4.6;12.6 Development of the Appetite Regulatory System;254
7.4.7;12.7 Programming of SNS Activity, Obesity, and Hypertension;256
7.4.8;12.8 Perspectives;258
7.4.9;References;258
7.5;13 High-Carbohydrate Intake Only During the Suckling Period Results in Adult-Onset Obesity in Mother as well as Offspring;264
7.5.1;13.1 Introduction;264
7.5.2;13.2 Metabolic Programming of the Fetus for Adult-Onset Disease;265
7.5.3;13.3 Altered Dietary Experience in the Immediate Postnatal Period (Suckling Period);266
7.5.4;13.4 The High-Carbohydrate (HC) Rat Model;266
7.5.5;13.5 Effects of the HC Milk Formula Observed in Rat Pups (F0) During the Period of the Dietary Modification;268
7.5.6;13.6 Long-Term Effects of the HC Dietary Modification Observed in Adulthood;268
7.5.7;13.7 The Transgenerational Effect of HC Dietary Modification;269
7.5.8;13.8 The HC Female Rat (F0) in the Prepregnancy Period;269
7.5.9;13.9 The HC Pregnant Rat (F0 Generation);269
7.5.10;13.10 The HC Fetus (F1 Generation);271
7.5.11;13.11 The HC Offspring (F1) in the Postnatal Period;272
7.5.12;13.12 Reversal of the Transgenerational Effect;273
7.5.13;13.13 Maternal Obesity due to High-Fat Diet Consumption and Programming Effects on the Offspring;274
7.5.14;13.14 Mechanisms Supporting the Phenomenon of Metabolic Programming;275
7.5.15;13.15 Conclusions;275
7.5.16;References;277
7.6;14 Prenatal Stress, Glucocorticoids, and the Metabolic Syndrome;281
7.6.1;14.1 Early Life Programming;281
7.6.2;14.2 The Role of Glucocorticoids;282
7.6.3;14.3 Glucocorticoids and Fetal Development;282
7.6.4;14.4 11ß-Hydroxysteroid Dehydrogenase Type 2 and the Feto-placental Glucocorticoid Barrier;283
7.6.5;14.5 Glucocorticoid Programming;285
7.6.6;14.6 Programming of Cardiovascular and Metabolic Systems;286
7.6.6.1;14.6.1 Programming of Blood Pressure and Vascular Function;286
7.6.6.2;14.6.2 Programming of Glucose and Insulin Homeostasis;287
7.6.6.3;14.6.3 Programming of the Pancreas;289
7.6.6.4;14.6.4 Fatty Liver;289
7.6.6.5;14.6.5 Programming of Muscle and Fat;290
7.6.7;14.7 Evidence for Glucocorticoid Programming in Humans;290
7.6.8;14.8 Mechanisms of Early Life Programming;292
7.6.9;14.9 Conclusions and Implications for Human Health;292
7.6.10;References;293
7.7;15 Hypothalamic Fetal Programming of Energy Homeostasis;303
7.7.1;15.1 Introduction;303
7.7.2;15.2 Prenatal Programming and Obesity;304
7.7.2.1;15.2.1 Epidemiological Studies;304
7.7.2.1.1;15.2.1.1 Human Maternal Undernutrition;304
7.7.2.1.2;15.2.1.2 Human Maternal Overnutrition;304
7.7.2.2;15.2.2 Animal Studies;305
7.7.3;15.3 Models to Induce Prenatal Maternal Undernutrition;305
7.7.3.1;15.3.1 Caloric Restriction;305
7.7.3.2;15.3.2 Protein Restriction;306
7.7.4;15.4 Models to Induce Prenatal Maternal Overnutrition;306
7.7.4.1;15.4.1 High-Fat Diet;306
7.7.4.2;15.4.2 Gestational Diabetes Mellitus (GDM);308
7.7.5;15.5 Central Mechanisms for Fetal Programming;308
7.7.5.1;15.5.1 Perinatal Hypothalamic Controls of Energy Homeostasis;308
7.7.5.2;15.5.2 Perinatal Leptin;310
7.7.6;15.6 Abnormal Hypothalamic Regulation of Fetal Programming;312
7.7.6.1;15.6.1 Fetal Hypothalamic Alterations in Maternal Overnutrition;312
7.7.6.2;15.6.2 Fetal Hypothalamic Alterations in Maternal Undernutrition;314
7.7.7;15.7 Conclusions;316
7.7.8;References;317
7.8;16 Adipocyte Development and Experimental Obesity;322
7.8.1;16.1 Introduction;322
7.8.2;16.2 Mechanisms of Adipose Tissue Growth and Function;323
7.8.2.1;16.2.1 Hyperplasia Versus Hypertrophy;323
7.8.2.2;16.2.2 Adipocyte Hypertrophy and Lipogenesis;327
7.8.2.3;16.2.3 Adipocyte Lipolysis;328
7.8.3;16.3 Endocrinology of Adipose Tissue;328
7.8.4;16.4 Prenatal Development of Adipose Tissue Depots;329
7.8.4.1;16.4.1 White Adipose Tissue;329
7.8.4.2;16.4.2 Brown Adipose Tissue;330
7.8.4.3;16.4.3 Developmental Origins of WAT Versus BAT;331
7.8.4.4;16.4.4 Body Fat Distribution;331
7.8.5;16.5 The Prenatal Nutritional Environment, Body Composition, and Obesity Risk;332
7.8.5.1;16.5.1 Prenatal Undernutrition, Low Birth Weight, and Adiposity;332
7.8.5.2;16.5.2 Role of Accelerated Postnatal Growth (''Catch-Up Growth'');333
7.8.6;16.6 Prenatal Undernutrition, LBW, and Adipocyte Biology;335
7.8.6.1;16.6.1 Adipogenesis, Lipogenesis, and Lipolysis in SGA Humans;335
7.8.6.2;16.6.2 Adipogenesis, Lipolysis, and Lipogenesis in Experimental Models;336
7.8.7;16.7 Hormone Signaling in SGA-Associated Obesity and Experimental Models;337
7.8.8;16.8 Adipokines in SGA-Associated Obesity and Experimental Models;339
7.8.9;16.9 Future Directions: Potential Role of Epigenetic and Developmental Mechanisms in Prenatal Undernutrition-Associated Obesity;340
7.8.10;16.10 Conclusions;341
7.8.11;References;342
8;Part IV Environmental Obesogens;354
8.1;17 The Obesogen Hypothesis of Obesity: Overview andINTtie;Human Evidence;355
8.1.1;17.1 Introduction;355
8.1.2;17.2 Developmental Origins of Health and Disease Paradigm;356
8.1.3;17.3 Environmental Toxicants;357
8.1.4;17.4 The Obesogen Hypothesis of Obesity;358
8.1.5;17.5 Human Data Supporting the Obesogen Hypothesis of Obesity;360
8.1.5.1;17.5.1 Smoking;360
8.1.5.2;17.5.2 Persistent Organic Pollutants;361
8.1.6;17.6 Adult Exposures to Environmental Agents and Obesity;362
8.1.6.1;17.6.1 Fructose;362
8.1.6.2;17.6.2 Monosodium Glutamate (MSG);362
8.1.6.3;17.6.3 Phthalates;363
8.1.7;17.7 Recommendations;363
8.1.8;References;364
8.2;18 Perinatal Exposure to Endocrine Disrupting Chemicals with Estrogenic Activity and the Development of Obesity;366
8.2.1;18.1 Introduction;366
8.2.2;18.2 The Developmental Origins of Adult Disease;367
8.2.3;18.3 Experimental Evidence for Involvement of Environmental Estrogens in Obesity;369
8.2.4;18.4 Diethylstilbestrol (DES);369
8.2.5;18.5 Bisphenol A;374
8.2.6;18.6 Phytoestrogens;376
8.2.7;18.7 Other EDCs;376
8.2.8;18.8 Proposed Modes of Action;377
8.2.9;18.9 Conclusions;377
8.2.10;References;378
8.3;19 The Role of Environmental Obesogens in the Obesity Epidemic;382
8.3.1;19.1 Introduction;382
8.3.2;19.2 An Archetype for Prenatal Chemical Exposure Leading to Obesity (Obesogens): Tributyltin;383
8.3.3;19.3 Obesogens Acting on Estrogen/Androgen Metabolism;384
8.3.4;19.4 Obesogens Acting on Glucocorticoid Metabolism;386
8.3.5;19.5 Obesogens Acting on Peroxisome Proliferator-Activated Receptors;388
8.3.6;19.6 Epigenetics: The GeneEnvironment Connection;389
8.3.7;19.7 Conclusion;391
8.3.8;References;392
9;Index;399