Novel Insights into Adipose Cell Functions (eBook)

Foreword 6
Contents 8
Contributors 10
Pathological Alteration of Human Adipose Tissue in Obesity 14
1 Natural History of Human Obesity 14
2 Human White Tissue in Obesity: Inflammation, Metabolic Dysfunction and Fibrosis 15
3 Adipose Cell Plasticity 17
4 Multiple Inflammatory Cells Involved 18
5 Perturbed Phenotypes of Preadipocytes and Adipocytes by Inflammation 19
6 Importance of the Extracellular Matrix 20
7 Specific Roles of Chemokines in Human Adipose Tissue: Example of Rantes/CCL5 20
8 Somatic Consequences of Inflammation: Visceral Adipose Tissue, Fatty Acids, Adipokines and Lipokines as the Guilty Players 21
9 Conclusion 22
References 23
Dynamics of Human Adipose Tissue. Regulatory Mechanisms and Consequences for Fat Cells and the Whole Body 27
1 Background 27
2 Age of Human Fat Cells 28
3 Adipose Cellularity 29
4 Clinical Consequences of Adipose Tissue Cellularity 30
5 Conclusions 31
References 31
Metabolism of Fatty Acids in Adipocytes 32
1 Introduction 32
2 De Novo Lipogenesis 33
3 Lipoprotein Lipase and FA Uptake 34
4 FA Esterification 38
5 Lipolysis 39
6 Triglyceride-fatty Acid Cycle 41
7 BAT and Fatty Acid beta-Oxidation 44
8 Therapeutic Perspectives 47
References 48
The Role of Hypoxia in Adipocyte Function and Dysfunction 55
1 Introduction 56
2 Hypoxia in Adipose Tissue in Obesity 57
3 Molecular Markers of Hypoxia 58
4 Hypoxia and Adipocyte Function 59
5 Hypoxia and Inflammatory Adipokines in Human Adipocytes 60
6 Glucose and Oxidative Metabolism 62
7 Pathological Implications of Hypoxia-induced Changes in Adipocytes: Insulin Resistance 64
8 Preadipocytes 65
9 Coda 67
References 67
Brown Adipose Tissue In Humans: A New Target for Anti-Obesity Therapy 71
1 Introduction 71
2 Origin of BAT 72
3 Genes and Signaling Pathways in BAT 73
4 Future Development 74
4.1 Activation, Substrate Preference, and Metabolic Role of Human BAT 74
4.2 Are There Different Kinds of hBAT? 75
References 75
Adipose Tissue Dysfunction: A Multistep Process 77
1 Introduction 77
2 What Gets it All Started: Hypoxia 78
3 The Extracellular Matrix in Adipose Tissue: A Source of Stress 79
4 Inflammation: A Late Stage Phenomenon? 81
5 Good Fat Pads and Bad Fat Pads 82
6 The Unfolded Protein Response, an Additional Stressor for Adipose Tissue 83
References 84
Fat Cell Progenitors: Origins and Plasticity 86
1 Introduction 86
2 Developmental Origins of Adipocytes 87
3 Human Adipose Tissue Contains a Pool of Adipocyte Progenitors 90
4 Human Adipose-Derived Stem (hMADS) Cell as a Cellular Model for Investigating Self-renewal of Human Adipocyte Progenitors 90
5 Plasticity of hMADS Cells 91
6 hMADS Cells are Appropriate to Study Human Adipocyte Differentiation 92
7 FGF2 and Activin A, Both Secreted by hMADS Cells, are Key Regulators of Self-Renewal 93
References 94
Transcriptional Regulation of Brown and White Adipogenesis 97
1 White Fat Cells 97
2 Brown Fat Cells 98
References 99
Transcriptional Control of Gene Expression in Different Adipose Tissue Depots 101
1 Introduction 102
2 Identification of a Group of Genes Highly Expressed in Visceral White Adipose Depots 103
3 PPARgamma Represses Visceral White Gene Expression in a Synthetic Ligand-dependent Manner and Requires Helix 7 of its Ligand-binding Domain 104
4 The CCAAT/Enhancer Binding Protein a (C/EBPa) and C-Terminal Binding Proteins (CtBP1/2) Facilitate the Repressive Effects of PPARy 105
5 Conclusion 106
References 107
Epigenetic Approaches to Adipose Biology 109
1 Adipocytes, Health and Disease 110
2 The Transcriptional Basis of Adipogenesis 110
3 Epigenetic Approaches to Studies of Adipogenesis 112
4 Epigenetic Approaches to Other Aspects of Metabolism 114
5 Conclusions 116
References 117
Metabolic and Angiogenic Consequences of the Presence or Absence of UCP1 119
1 Introduction 119
2 In the Absence of UCP1, Brown Fat Cells Do Not Produce Heat 120
3 Does the Presence/Absence of UCP1 Affect Adaptive Nonshivering Thermogenesis? 121
4 Does the Presence/Absence of UCP1 Affect Adaptive Adrenergic Thermogenesis? 121
5 Does the Presence/Absence of UCP1 Affect Cold-Induced Angiogenesis? 122
6 Does the Presence/Absence of UCP1 Affect beta3-Adrenoceptor-Induced Thermogenesis and Weight Loss? 123
7 Does the Presence/Absence of UCP1 Affect Diet-Induced Thermogenesis? 123
8 Does the Presence/Absence of UCP1 Affect Leptin-Induced Thermogenesis? 124
9 What are the Consequences of a Lack of Diet-Induced Thermogenesis? 125
10 Does the Presence/Absence of UCP1 Affect Human Metabolism? 126
References 127
Metabolic Responses to Weight Perturbation 129
1 Introduction 129
2 Energetics of Weight Loss 130
3 Maintenance of a Reduced Body Weight 131
4 Compartments of Energy Expenditure 133
5 Energy Intake 136
6 Formulation of Mechanisms 136
7 Implications 138
8 Conclusions 139
References 139
Understanding Causal Relationships in the Metabolic Syndrome: Recent Insights from Extreme Human Phenotypes 142
1 Introduction 143
2 Insulin Resistance, Dyslipidaemia and Fatty Liver 143
3 Novel Autosomal Recessive Form of Partial Lipodystrophy 146
4 Peripheral Defect in GLUT4 Translocation 147
5 Conclusions 149
References 149
Index 152