This textbook presents for the first time a comprehensive body of the latest knowledge in the field of neuropeptides and their action on energy balance. It contains a detailed and comprehensive account of the specific hypothalamic peptides in regards to their roles in energy balance, food intake control and co-morbidities, to better understand the patho-physiology of obesity.
The textbook includes an examination the history of the evolution of human society from a thin to the obese phenotype and, within that context, how modern society habits and industrial food production did not respect the evolutionary trait resulting in changes in the energy balance set point. It provides a novel conceptualization of the problem of obesity when considering the biochemistry of peptide hormones and entertaining novel ideas on multiple approaches to the problems of energy balance, as well as demonstrates and explains why alterations in pro-hormone processing are paramount to understand metabolic disease.
This text is excellent material for teaching graduate and medical school courses, as well as a valuable resource for researchers in biochemistry, cell, and molecular biology, neuroscientists, physician endocrinologists, and nutritionists.
Author(s): Eduardo A. Nillni
Edition: 1
Publisher: Springer INternational Publishing
Year: 2018
Language: English
Pages: 379
City: Cham
Tags: nutrient sensors thyrotropin releasing hormone endoplasmic reticulum stress leptin obesity prohormones neuroendocrinology
Dedication......Page 5
Preface......Page 6
Contents......Page 10
Contributors......Page 12
Part I: Evolution and Origens of Obesity......Page 14
1.2 Brain Evolution and Changes in Human Nutrition......Page 15
1.3 Definition of Obesity......Page 18
1.4 Nutritional Balance, Metabolic and Hedonic Set Point......Page 21
1.5 Evolutionary Traits......Page 26
1.6 Thermogenesis and Human Migration......Page 30
1.7 Conclusions and Further Thoughts......Page 31
References......Page 34
Part II: The Hypothalamus......Page 38
2.1 Introduction......Page 39
2.2 The Hypothalamus......Page 40
2.3 The Arcuate Nucleus (ARC) of the Hypothalamus......Page 44
2.4 Paraventricular Nucleus (PVN)......Page 47
2.5 Lateral Hypothalamus Area......Page 49
2.7 Ventromedial Nucleus......Page 50
2.9 Peripheral Signals Leptin and Insulin Involved in Energy Homeostasis......Page 51
2.10 Conclusions......Page 54
References......Page 56
3.1 Transcriptional Mechanisms......Page 65
3.1.1.2 Hypothalamic Cell Lines......Page 66
3.1.1.3 In Vivo Methods and Models......Page 67
3.1.2 Hypothalamic Promoter Regions......Page 68
3.1.3 Hypothalamic Transcription Factors......Page 71
3.1.4 DNA and Histone Modification......Page 72
3.1.6 POMC Neurons in Response to Increased Energy Availability......Page 73
3.1.7 Responses to Fasting and Reduced Energy Availability......Page 76
3.2 Summary and Key Questions that Remain Unanswered......Page 78
References......Page 79
4.1 Inflammation......Page 84
4.1.1 Hallmarks of Inflammation......Page 85
4.1.2.1 Neurons Are Not Alone in the CNS......Page 87
4.1.2.2 Hypothalamic Inflammation and Energy Homeostasis......Page 88
4.2 Endoplasmic Reticulum Stress and Unfolded Protein Response......Page 93
4.2.1 ER Stress and the Regulation of Energy Balance......Page 98
4.2.2 Hypothalamic ER Stress and Neuropeptides......Page 102
4.3 Conclusion......Page 104
References......Page 106
5.1 Introduction......Page 118
5.2 Origin of the Prohormone Theory and Biosynthesis of Inactive Prohormone Precursors......Page 119
5.3 The Family of Prohormone Convertases (PCs) and Their Cellular Traffic and Action on Key Neuropeptide Prohormones: History of PCs on Prohormones......Page 120
5.4 Traffic of Prohormones and Its Derivate Peptides to the Regulated Secretory Pathway......Page 125
5.5 Pro-thyrotropin-Releasing Hormone......Page 131
5.6 Pro-opiomelanocortin......Page 134
5.7 Pro-corticotropin-Releasing Hormone CRH......Page 137
5.8 Conclusions......Page 139
References......Page 140
6.1 Introduction......Page 149
6.2 Cellular Nutrient Sensors......Page 151
6.2.1 mTOR......Page 152
6.2.2 AMPK......Page 153
6.2.3 Histone Deacetylases: Sirtuins and Classical HDACs......Page 154
6.3.1 mTOR......Page 157
6.3.2 AMPK......Page 159
6.3.3 Histone Deacetylases: Sirtuins and Classical HDACs with Special Emphasis on SIRT1......Page 160
6.4 Prohormone Processing and Prohormone Convertases......Page 162
6.4.1 SIRT1 Regulates POMC and AgRP Peptides......Page 163
6.4.2 SIRT1 Regulates proCRH......Page 169
6.5 Concluding Remarks......Page 172
References......Page 173
Part III: Peripheral Contributors Participating in Energy Homeostasis and Obesity......Page 189
7: Gastrointestinal Hormones Controlling Energy Homeostasis and Their Potential Role in Obesity......Page 190
7.1 Introduction: General Aspects of Gastrointestinal Hormones......Page 191
7.2 Ghrelin......Page 192
7.3 Cholecystokinin......Page 194
7.4 Glucagon-Like Peptide-1......Page 196
7.5 PYY......Page 197
7.6 Other Gastrointestinal Hormones......Page 199
7.7 Gastrointestinal Hormones and Obesity......Page 200
References......Page 204
8.1 Types of Adipose Tissue and Adipocytes......Page 211
8.2 Depots and Depot Differences in AT......Page 212
8.3 Cellular and Noncellular Composition of WAT/BAT......Page 215
8.4 Endocrine Function of AT......Page 218
8.5 Control of Lipolysis and Lipogenesis......Page 219
8.6 Ectopic Fat Deposition/Lipodystrophy......Page 220
8.7 AT Remodeling......Page 221
References......Page 223
9.1 General......Page 230
9.2 Insulin Signaling and Resistance......Page 231
9.2.1 Insulin Signaling......Page 232
9.2.2 Insulin Resistance......Page 233
9.3 Inflammation in Adipose Tissue......Page 235
9.3.1 Adipose Tissues......Page 236
9.3.2 Immune Responses in Adipose Tissues......Page 237
9.4 Adipokines......Page 239
9.4.1.1 Leptin......Page 240
9.4.1.3 Interleukin-6......Page 241
9.4.1.5 CC Chemokine Ligand Type 2 (CCL2) and CC Chemokine Receptor Type 5 (CCR5)......Page 242
9.4.1.8 Dipeptidyl Peptidase-4 (DPP-4)......Page 243
9.4.2.1 Adiponectin......Page 244
9.4.2.3 Secreted Frizzled-Related Protein 5 (SFRP5)......Page 245
9.4.2.6 Apelin......Page 246
9.5 Adipokines and the Neuroendocrine System......Page 247
References......Page 248
Part IV: Neuroendocrine Axes and Obesity......Page 258
10.1.1 The Regulation of Thyroid Hormone Levels......Page 259
10.1.2 The Role of Thyroid Hormone in Gene Regulation......Page 262
10.2 Thyroid Hormone’s Role in Body Weight Regulation......Page 264
10.2.1 Thyroid Hormone Has Direct and Indirect Effects on Metabolism......Page 265
10.2.2 Thyroid Hormone as a Treatment for Obesity......Page 266
10.3 The Effects of Weight Loss on Thyroid Hormone......Page 267
10.4 Conclusions......Page 268
References......Page 269
11.1 The Melanocortin System: Proopiomelanocortin......Page 275
11.2 Melanocortin Receptors......Page 277
11.3 Beta-Endorphin......Page 279
11.4 The Stress Response: Overview......Page 282
11.5 Melanocortins and the Physiologic Stress Response......Page 285
11.6 Melanocortins and Immune Function......Page 286
11.7 Melanocortins and Pain Pathways......Page 288
11.8 Melanocortins and the Behavioral Responses to Stress......Page 289
11.9.1 Food Insecurity and Obesity......Page 291
11.9.2 Acute Stress and Body Weight......Page 292
11.9.3 Chronic Stress and Body Weight......Page 294
11.9.4 Obesity-Induced “Stress”......Page 297
11.10 Conclusions......Page 298
References......Page 301
12.1 Introduction to the growth hormone/insulin-like growth factor (GH/IGF-1) Axis......Page 324
12.2 Role of GH in Nutrient Metabolism......Page 326
12.3.1 Acromegaly and Gigantism......Page 328
12.3.3 Laron Syndrome (LS)......Page 329
12.3.6 Decreased GH Action......Page 330
12.4.1 Body Composition......Page 332
12.4.2 Adipokines......Page 333
12.4.4 GH as a Treatment Modality for Obesity? Pros vs Cons......Page 335
References......Page 338
Part V: Nutrition......Page 348
13.1.1 Conflicting Theories of Hedonically Motivated Food Intake......Page 349
13.1.2 Dynamic Theory of Hedonically Motivated Food Intake......Page 350
13.2.1 The Impact of Food Volume Driving Intake......Page 351
13.2.3 Individual Differences in Environmental Response......Page 352
13.3.1 Food-Specific Aberrant Response in Obesity......Page 353
13.3.2 Generalized Reward Sensitivity and Impulsivity......Page 354
13.4.1 Neural and Genetic Risk Factors of Overeating and Weight Gain......Page 355
13.4.1.1 Genetic Influences on Brain Response to Food and Weight Regulation......Page 356
13.4.2 Brain-Based Predication and Consequences of Weight Gain and Overeating......Page 357
13.5.1 Leptin......Page 358
13.5.2 Insulin......Page 359
13.5.3 Ghrelin......Page 361
13.5.4 Glucagon-like Peptide-1......Page 362
References......Page 363
Index......Page 372
