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Adipose Tissue in Health and Disease

Todd Leff (Editor), James G. Granneman (Editor)
ISBN: 978-3-527-31857-5
530 pages
April 2010, Wiley-Blackwell
Adipose Tissue in Health and Disease (3527318577) cover image

Description

This timely and most comprehensive reference available on the topic covers all the different aspects vital in the fight against the global obesity epidemic.
Following a look at adipose tissue development and morphology, the authors go on to examine its metabolic and endocrine functions and its role in disease. The final section deals with comparative and evolutionary aspects of the tissue.
The result is an essential resource for cell and molecular biologists, physiologists, biochemists, pharmacologists, and those working in the pharmaceutical industry.
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Table of Contents

Preface XIX

List of Contributors XXI

Part One Adipose Tissue Development and Morphology 1

1 Transcriptional Control of Adipogenesis and Fat Cell Gene Expression 3
Ursula A. White and Jacqueline M. Stephens

1.1 Introduction 3

1.2 Transcriptional Control of Adipogenesis 4

1.3 Identification of Adipocyte Transcription Factor Target Genes 9

References 14

2 Cellular and Molecular Basis of Functional Differences among Fat Depots 21
Thomas Thomou, Tamara Tchkonia, and James L. Kirkland

2.1 Introduction 21

2.2 Physiology 27

2.3 Conclusions 35

References 36

3 Plasticity of the Adipose Organ 49
Saverio Cinti

3.1 Introduction 49

3.2 Gross Anatomy Demonstrates that WAT and BAT are Mixed Together in the Adipose Organ 50

3.3 Light and Electron Microscopy show that White and Brown Adipocytes have a Well-Defined and Distinct Morphology 51

3.4 WAT and BAT have a Different Vascular and Nerve Supply 53

3.5 WAT and BAT have a Different Physiology 54

3.6 Phenotype of the Adipose Organ is Variable: Plasticity of the Adipose Organ 55

3.7 Adipose Organ of Humans 61

References 63

4 Biology of Adipose Tissue Stem Cells 69
Jeffrey M. Gimble, Bruce A. Bunnell, and Farshid Guilak

4.1 Introduction 69

4.2 In Situ Localization and Embryology 69

4.3 Isolation Methods 70

4.4 Characterization 71

4.5 Differentiation and Potential Utility for Regenerative Medicine 73

4.6 Conclusions 74

References 74

Part Two Metabolic Functions of Adipose Tissue 81

5 Molecular Mechanisms of Adipocyte Lipolysis 83
James G. Granneman and Hsiao-Ping H. Moore

5.1 Introduction 83

5.2 Key Players in Adipocyte Lipolysis 83

5.3 Lipolytic Protein Trafficking 88

5.4 Working Model and Unresolved Issues 91

References 93

6 New Developments in the Lipolytic Processing of Triglyceride-Rich Lipoproteins 97
André Bensadoun, Anne P. Beigneux, Loren G. Fong, and Stephen G. Young

6.1 Introduction 97

6.2 LPL 98

6.3 Functional Domains of LPL 99

6.4 Regulation of LPL Activity by Angiopoietin-Like Proteins 100

6.5 Role of GPIHBP1 in the Lipolysis of Triglyceride-Rich Lipoproteins 101

6.6 Role of Apo-AV in Lipolysis 103

6.7 Newly Discovered Regulators of LPL Activity and their Physiological Significance 104

References 105

7 Intracellular Fatty Acid Transport, Activation, and Trafficking 109
Doug Mashek

7.1 Introduction 109

7.2 Fatty Acid-Binding Protein Family 109

7.3 Fatty Acid Activation and Channeling: Role of Long-Chain Acyl-CoA Synthetases and Fatty Acid Transport Proteins 113

7.4 Role of Acyl-CoA-Binding Protein in Acyl-CoA Metabolism 116

7.5 Regulation and Function of Distinct Fatty Acid and Acyl-CoA Pools 117

7.6 Contribution of Fatty Acid and Acyl-CoA Metabolism to Metabolic Diseases 119

7.7 Conclusions 121

References 121

8 Aquaporins and Adipose Tissue: Lesson from Discovery to Physiopathology and to the Clinic of Aquaporin Adipose (AQP7) 129
Ken Kishida

8.1 Introduction 129

8.2 Characteristics of Adipocytes and Gycerol Metabolism in the Mammalian Body 130

8.3 Adipose Glycerol Channel: AQP7 132

8.4 Hepatic Glycerol Channel: AQP9 141

8.5 Coordination of Adipose Glycerol Channel, AQP7, and Hepatic Glycerol Channel, AQP9 143

8.6 Dysregulation of AQP7 and AQP9 in Obesity with Insulin Resistance 143

8.7 Conclusions 144

References 144

9 Signaling Pathways Controlling Lipolysis and Lipid Mobilization in Humans 149
Max Lafontan

9.1 Introduction 149

9.2 Role of Lipases in the Regulation of Hydrolysis of Fat Cell Triacylglycerols 151

9.3 Adrenergic Control of cAMP Production, Lipolysis and Lipid Mobilization 152

9.4 Control of cAMP Production by Adenylyl Cyclase Inhibitors – Inhibition of Lipolysis 157

9.5 Insulin: A Major Antilipolytic Agent Controlling cAMP Degradation 158

9.6 Natriuretic Peptides Control cGMP Production, Lipolysis, and Lipid Mobilization in Humans 159

9.7 Other Lipolytic Pathways 163

9.8 Future Trends and Pharmacological Prospects 167

References 168

Part Three Endocrine Functions of Adipose Tissue 181

10 Leptin Secretion and Action 183
Robert V. Considine

10.1 Introduction 183

10.2 Leptin Synthesis 184

10.3 Leptin Receptors 187

10.4 Leptin Action in the Central Nervous System 187

10.5 Leptin Resistance in Obesity 189

10.6 Metabolic Complications of Hyperleptinemia in Obesity 190

10.7 Leptin Therapy in Humans 192

10.8 Conclusions 194

References 194

11 Adiponectin 201
Jonathan P. Whitehead and Ayanthi A. Richards

11.1 Introduction 201

11.2 Adiponectin Structure and Post-Translational Modifications 202

11.3 Significance and Bioactivity of Adiponectin Multimers 204

11.4 Adiponectin and Liver 205

11.5 Adiponectin and Skeletal Muscle 206

11.6 Adiponectin and the Vasculature 206

11.7 Adiponectin and the Brain 207

11.8 Adiponectin Expression and Secretion 208

11.9 Adiponectin Secretion 209

11.10 Ectopic Adiponectin Expression 211

11.11 Regulation of Expression and Secretion 212

11.12 Adiponectin Clearance 214

11.13 Adiponectin Receptors and Downstream Effectors 215

11.14 Adiponectin Signaling 216

11.15 Conclusions 217

References 218

12 Preadipocyte factor-1 and Adipose Tissue-Specific Secretory Factor/Resistin – Two Secreted Factors from Adipose Tissue: Role in Adipogenesis and Insulin Resistance 231
Hei Sook Sul, Yuhui Wang, and Carolyn Hudak

12.1 Introduction 231

12.2 Pref-1 Structure 232

12.3 Pref-1 Inhibition of Adipocyte Differentiation 233

12.4 Mechanism for Pref-1 Function 234

12.5 In Vivo Effect of Pref-1 on Adipogenesis and Glucose/Insulin Homeostasis 235

12.6 ADSF/Resistin: Identification and Structure 236

12.7 ADSF/Resistin Expression and Function 237

12.8 Conclusions 239

References 240

13 Adipose Tissue and Blood Pressure Regulation 245
Lisa A. Cassis and Sara B. Police

13.1 Introduction 245

13.2 Adipose Tissue Changes with Obesity: Relation to Blood Pressure Control 245

13.3 Regional Adipose Deposition and Blood Pressure Regulation 254

13.4 Conclusions 256

References 257

14 Adipokines, Inflammation, and Obesity 265
Karine Clément

14.1 Introduction 265

14.2 Contribution of Adipose Tissue in Systemic Inflammation during Obesity 266

14.3 Adipose Tissue Depots and Adipokine Production 268

14.4 Adipokines and Adipose Tissue Cell Types 269

14.5 Adipokines, Macrophages, and the Biology of Adipocytes 270

14.6 Adipokines and Complications of Obesity 274

14.7 Adipokines and Weight Loss 275

14.8 Conclusions 276

References 276

Part Four Adipose Tissue and Disease 283

15 Depot-Specific Biology of Adipose Tissues: Links to Fat Distribution and Metabolic Risk 285
Mi-Jeong Lee and Susan K. Fried

15.1 Introduction 285

15.2 Adipose Depots: Definitions 286

15.3 Physiological and Anatomical Differences among Depots may Drive Functional Heterogeneity 286

15.4 Heterogeneity in Adipocyte Function among Adipose Depots 288

15.5 Regional Differences in Adipose Tissue Gene Expression and Protein Production: Relationship to the Metabolic Syndrome 291

15.6 Search for Novel Adipokines with Depot-Specific Expression that Link Regional Adiposity to Metabolic Risk 291

15.7 Importance of Adipose Tissue Macrophages and other Immunocytes in Regional Adipose Tissue Dysfunction 293

15.8 Gene Expression Profiles are Providing New Insights on Regional Adipose Growth and Function 295

15.9 Depot Differences in Cell Proliferation and Differentiation Capacity 296

15.10 Conclusions and Future Directions 297

References 298

16 Viral Induction of Obesity and Adipogenesis 307
Magdalena Pasarica, Rohan N. Dhurandhar, Nazar Mashtalir, and Nikhil V. Dhurandhar

16.1 Introduction 307

16.2 Viruses 313

16.3 Chlamydia pneumoniae 320

16.4 Gut Microbiota 320

16.5 Gut Parasites 321

16.6 Scrapie Agents 322

16.7 Interaction of Pathogens and Adipose Tissue 323

16.8 Adipogenic Pathogens and Humans 324

16.9 Conclusions 324

References 325

17 Adipose Tissue Cachexia 333
Michael John Tisdale

17.1 Introduction 333

17.2 Changes in Adipose Tissue in Cachexia 333

17.3 Energy Expenditure in Cancer Patients 335

17.4 Factors Governing Adipose Tissue Mass 336

17.5 Mechanism of Loss of Adipose Tissue in Cachexia 337

17.6 Requirements of Tumor-Bearing Animals for Lipids 338

17.7 Fat-Mobilizing Substances in Cancer Cachexia 338

17.8 Conclusion 340

References 342

18 Obesity and Diabetes: Lipotoxicity 347
Christopher J. Lelliott, Matej Ore4si4c, and Antonio J. Vidal-Puig

18.1 Introduction 347

18.2 White Adipose Tissue at the Center of Lipid Homeostasis and Delivery 348

18.3 Insulin Resistance in Adipocytes Disrupts the Balance between Lipid Storage and Secretion 348

18.4 Scenarios that may Result in Ectopic Fat Deposition 348

18.5 Mechanisms Contributing to the Lipotoxicity in the Peripheral Organs 355

18.6 Impaired Oxidation as a Trigger for Lipotoxicity 360

18.7 Pancreatic b-Cell as a Target for Lipotoxicity 363

18.8 New Analytical and Computational Methods to Identify Lipotoxicity-Related Metabolic Networks 363

18.9 Lessons from Lipotoxicity – Potential Antilipotoxic Therapeutic Strategies 365

References 365

19 Obesity and Cancer 369
Andrew G. Renehan

19.1 Introduction 369

19.2 Epidemiology 369

19.3 Biological Mechanisms 371

19.4 Other Biological Candidates 380

19.5 Mechanical Mechanisms 381

19.6 New Research Areas 382

References 382

20 Overview of Acquired and Genetic Lipodystrophies 385
Tisha Joy and Robert A. Hegele

20.1 Introduction 385

20.2 Congenital Lipodystrophies 386

20.3 Acquired Lipodystrophies with a Possible Genetic Component 393

20.4 Lipodystrophy Associated with other Syndromes 395

20.5 Conclusions 397

References 398

21 Mouse Models of Lipodystrophy 403
Jimmy Donkor and Karen Reue

21.1 Introduction 403

21.2 Physiological Mechanisms of Lipodystrophy in Mouse Models 403

21.3 Lipodystrophic Models with Impaired Adipogenesis 407

21.4 Lipodystrophic Models with Impaired Triacylglycerol Biosynthesis 411

21.5 Lipodystrophic Models with Enhanced Energy Expenditure 414

21.6 Mouse Models with Acquired or Conditional Lipodystrophy 416

21.7 Conclusions 418

References 419

22 Caloric Restriction, Longevity, and Adiposity 423
Leanne M. Redman and Eric Ravussin

22.1 Introduction 423

22.2 Physiological Changes with Aging 424

22.3 Aging and Caloric Restriction 424

22.4 Energy Restriction may Alter the ‘‘Rate of Living’’ 425

22.5 CR and Oxidative Stress 426

22.6 CR and Cardiovascular Disease 427

22.7 CR and Insulin Resistance/Type 2 Diabetes Mellitus 427

22.8 What is Known from Humans? 427

22.9 Could CR Increase Longevity in Humans? 431

22.10 CR Mimetics 433

22.11 Conclusions 434

References 434

23 Peroxisome Proliferator-Activated Receptor-c: A Key Regulator of Adipose Tissue Formation, Remodeling, and Metabolism 441
Olga Astapova and Todd Leff

23.1 Introduction 441

23.2 Molecular Biology of PPAR-c 442

23.3 PPAR-c is a Master Regulator of Adipose Tissue Development 447

23.4 Metabolic Functions of PPAR-c 449

23.5 White versus Brown Fat-Specific Functions of PPAR-c 450

23.6 PPAR-c Function in Adipose Tissue Maintenance and Remodeling 452

23.7 Conclusions 454

References 454

24 Early-Life Programming of Adipogenesis and Adiposity 459
Roselle L. Cripps and Susan E. Ozanne

24.1 Introduction 459

24.2 Theories for the Developmental Origins of Obesity 460

24.3 Evidence for the Developmental Origins of Obesity 460

24.4 Adipogenesis 462

24.5 Potential Mechanisms? 465

24.6 Future Perspectives 467

References 468

25 Evolutionary Aspects of Obesity and Adipose Tissue Function 473
Jonathan C. K. Wells

25.1 Introduction 473

25.2 Thrifty Genotype and Phenotype Hypotheses 474

25.3 Ethological Approach 476

25.4 Significance of Agriculture 482

25.5 Significance of Colonizing 483

25.6 Significance of Social Inequality 485

25.7 New Obesogenic Environment 486

References 487

Index 491

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Author Information

Todd Leff is Associate Professor in the Department of Pathology at the Wayne State University School of Medicine in Detroit, Michigan. In 1991 he moved to the Parke-Davis Company where he became the Director of the Transcription Research Group in the Department of Cell biology. In 2002 he joined the faculty at the Wayne State. He serves on the editorial boards of the Journal of Biological Chemistry, the Journal of Lipid Research and the American Journal of Physiology.

James Granneman is Professor of Psychiatry and Behavioral Neurosciences, and Pathology at Wayne State University School of Medicine. Dr. Granneman's research interests include lipolysis and adrenergic signal transduction in adipose tissues, and he serves on the editorial board of American Journal of Physiology.
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