Cellular Lipid Metabolism (eBook)

Preface 5
Contents 7
Contributors 14
Chapter 1 The Lipid Droplet: a Dynamic Organelle, not only Involved in the Storage and Turnover of Lipids 18
1.1 Introduction 19
1.2 Lipid Droplets Form as Primordial Structures at Microsomal Membranes 20
1.3 Lipid Droplet Size Increases by Fusion 22
1.4 Lipid Droplets and the Development of Insulin Resistance 24
1.5 Lipid Droplet-Associated Proteins 25
1.6 Lipid Droplets and the Secretion of Triglycerides from the Cell 28
1.7 Conclusions 36
References 36
Chapter 2 Oxysterols and Oxysterol-Binding Proteins in Cellular Lipid Metabolism 44
2.1 Oxysterols, Their Synthesis and Catabolism 44
2.2 Biological Activities of Oxysterols 51
2.3 Cytoplasmic Oxysterol-Binding Proteins 58
2.4 Future Perspectives 72
References 75
Chapter 3 Cellular Lipid Traffic and Lipid Transporters: Regulation of Efflux and HDL Formation 89
3.1 Introduction 89
3.2 Regulation of apoA-I Synthesis, Lipidation and Secretion in Hepatocytes: Genesis of apoA-I-Containing Lipoproteins and HDL 90
3.3 Cell Specificity of ABCA1 Expression and HDL Formation in Vivo: Insight from Genetically Modified Mice 91
3.4 Transcriptional and Posttranscriptional Regulation of ABCA1 92
3.5 Cellular Traffic of ABCA1 94
3.6 Integrated Models of Lipid Efflux and Lipoprotein Assembly: Nascent HDL Formation 98
3.7 Complementarities of ABCA1, ABCG1 and SR-BI in Lipid Efflux and HDL Formation and Their Combined Role in Reverse Cholesterol Transport in Vivo 101
3.8 Cellular Lipid Traffic Through the Late Endosomes 104
3.9 Cholesterol Traffic Through the Lipid Droplet 107
3.10 Caveolin and Cellular Cholesterol Transport 110
3.11 Mobilization of LD Lipids for Efflux 111
3.12 Conclusions 113
References 114
Chapter 4 Bile Acids and Their Role in Cholesterol Homeostasis 123
4.1 Introduction 123
4.2 Bile Acid Synthesis 124
4.3 Regulation of the Enterohepatic Circulation 131
4.4 Cholesterol in the Enterohepatic Circulation 133
4.5 Role of the Enterohepatic Cycle in the Control of Cholesterol Homeostasis 139
4.6 Concluding Remarks 140
References 140
Chapter 5 Cholesterol Trafficking in the Brain 146
5.1 Introduction 146
5.2 Cholesterol Turnover in the Brain 147
5.3 Release of 24( S )-Hydroxycholesterol from the Brain into the Circulation 150
5.4 Lipoproteins in the Cerebrospinal Fluid 151
5.5 Astrocytes Supply Neurons with Cholesterol 152
5.6 How do Neurons Regulate Their Cholesterol Supply? 154
5.7 Alternative Pathway for Cholesterol Release from Neurons? 157
5.8 Role for cAMP Responsive Element Binding Protein in the Regulation of Neuronal Cholesterol Homeostasis 158
5.9 Internalization of Cholesterol by Neurons 158
5.10 The Choroid Plexus as an Alternative Source of HDL 159
5.11 Disturbances in Cholesterol Trafficking Between Astrocytes and Neurons in Alzheimer’s Disease? 160
5.12 Do Alterations in Systemic Sterol Metabolism Alter Brain Sterol Metabolism? 162
References 163
Chapter 6 Intracellular Cholesterol Transport 171
6.1 Biophysical Properties of Cholesterol in Model Membranes 171
6.2 Molecular Organization and Function of Cholesterol in the Plasma Membrane 175
6.3 Overview of Membrane Traffic Along the Endocytic and Secretory Pathways and its Dependence on Cholesterol 179
6.4 Function of Various Organelles in Cellular Cholesterol Metabolism and Transport 182
6.5 Vesicular and Non-Vesicular Transport of Cholesterol: Targets, Kinetics and Regulation 185
6.6 Alterations in Intracellular Cholesterol Trafficking in Atherosclerosis and Lipid Storage Diseases 190
6.7 Future Prospects 194
References 195
Chapter 7 Role of the Endothelium in Lipoprotein Metabolism 205
7.1 Introduction 205
7.2 Expression of Proteins Involved in Lipoprotein Metabolism 206
7.3 Lipoprotein Transport Through the Endothelium 209
7.4 Target for Physiological and Pathological Effects of Lipoproteins 214
References 220
Chapter 8 Receptor-Mediated Endocytosis and Intracellular Trafficking of Lipoproteins 227
8.1 Lipoproteins and Their Receptors 227
8.2 Receptor-Mediated Endocytosis of LDL 230
8.3 Receptor-Mediated Endocytosis of Chylomicron Remnants 237
References 244
Chapter 9 Angiopoietin-Like Proteins and Lipid Metabolism 250
9.1 Introduction 250
9.2 Angptl4 and Lipid Metabolism 251
9.3 Angptl3 and Lipid Metabolism 256
9.5 Conclusion 259
References 259
Chapter 10 Thyroid Hormones and Lipid Metabolism: Thyromimetics as Anti-Atherosclerotic Agents? 263
10.1 Thyroid Hormones, Thyroid Hormone-Receptors and Lipoprotein Metabolism 264
10.2 Thyromimetics and Thyromimetic Compounds 280
References 288
Chapter 11 Adipokines: Regulators of Lipid Metabolism 295
11.1 Introduction 295
11.2 Regulation of Lipid Metabolism by Adipokines 296
11.3 Conclusions 306
References 307
Chapter 12 Cellular Cholesterol Transport – Microdomains, Molecular Acceptors and Mechanisms 312
12.1 Overview 312
12.2 Structure and Properties of the Cell Surface 315
12.3 Role of Cell-Surface Lipid Transporters in RCT 316
12.4 Cholesterol Efflux and the LCAT Reaction 317
12.5 Significance of ABCG1 319
12.6 Recycling of apo-A-I 319
12.7 RCT from Activated Macrophages 320
References 322
Chapter 13 The Ins and Outs of Adipose Tissue 325
13.1 Introduction 326
13.2 Sources of Lipids for Deposition in Adipose Tissue 327
13.3 Lipoprotein Lipase 331
13.4 Intracellular Lipases 357
13.5 Triglyceride Synthesis 360
13.6 Conclusion: an Integrated View of the Lipase Systems in Adipose Tissue 363
References 364
Index 380