Cellular lipid metabolism:
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| Other Authors: | |
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| Format: | Book |
| Language: | English |
| Published: |
Berlin [u.a.]
Springer
2009
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XVIII, 376 S. Ill., graph. Darst. |
| ISBN: | 9783642002991 |
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Record in the Search Index
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| adam_text | Titel: Cellular lipid metabolism
Autor: Ehnholm, Christian
Jahr: 2009
Contents
1 The Lipid Droplet: a Dynamic Organelle, not only
Involved in the Storage and Turnover of Lipids 1
Sven-Olof Olofsson, Pontus Bostrom, Jens Lagerstedt,
Linda Andersson, Martin Adiels, Jeanna Perman,
Mikael Rutberg, Lu Li, and Jan Boren
1.1 Introduction 2
1.2 Lipid Droplets Form as Primordial Structures
at Microsomal Membranes 3
1.2.1 Microsomal Membrane Proteins Involved
in Lipid Droplet Formation 3
1.2.2 Model for the Assembly of Lipid Droplets 4
1.3 Lipid Droplet Size Increases by Fusion 5
1.3.1 SNAREs are Involved in Lipid Droplet Fusion 5
1.3.2 Model for the Fusion Between Lipid Droplets 6
1.4 Lipid Droplets and the Development of Insulin Resistance 7
1.5 Lipid Droplet-Associated Proteins 8
1.5.1 PAT Proteins 8
1.5.2 Other Lipid Droplet-Associated Proteins 11
1.6 Lipid Droplets and the Secretion of Triglycerides from the Cell 11
1.6.1 The Assembly and Secretion of Milk Globules 12
1.6.2 ApoBlOO: the Structural Protein of VLDL 13
1.6.3 ApoBlOO and the Secretory Pathway 14
1.6.4 The Assembly of VLDL 14
1.6.5 Regulation of VLDL Assembly 17
1.6.6 Clinical Implications of VLDL 1 Production 18
1.7 Conclusions 19
References 19
2 Oxysterols and Oxysterol-Binding Proteins
in Cellular Lipid Metabolism 27
Vesa M. Olkkonen
2.1 Oxysterols, Their Synthesis and Catabolism 27
2.1.1 Oxysterols that Arise Through Enzymatic
Cholesterol Oxidation 28
vii
viii Contents
2.1.2 Oxysterols Generated via Non-Enzymatic
Oxidative Events 31
2.1.3 Oxysterols in the Circulation 31
2.1.4 Catabolism of Oxysterols 33
2.2 Biological Activities of Oxysterols 34
2.2.1 Effects of Oxysterol Administration on Cells in Vitro 34
2.2.2 Oxysterols in Atherosclerotic Lesions 35
2.2.3 Oxysterols as Regulators of Cellular Lipid Metabolism 36
2.2.4 Oxysterols Regulate Hedgehog Signaling 40
2.3 Cytoplasmic Oxysterol-Binding Proteins 41
2.3.1 Indentification of Oxysterol-Binding
Protein-Related Proteins 41
2.3.2 Structure and Ligands of ORPs 42
2.3.3 Subcellular Distribution of ORPs 45
2.3.4 Function of OSBP in Lipid Metabolism 47
2.3.5 Evidence for the Involvement of Mammalian
OSBP Homologues in Lipid Metabolism 48
2.3.6 Functional Interplay of ORPs with the Transcriptional
Regulators of Lipid Metabolism 50
2.3.7 Function of Yeast Osh Proteins in Sterol Metabolism 50
2.3.8 Osh4p Regulates Secretory Vesicle Transport 52
2.3.9 Mammalian ORPs and Intracellular Vesicle Transport 53
2.3.10 ORPs - Integrating Lipid Cues with Cell
Signaling Cascades 54
2.4 Future Perspectives 55
References 58
3 Cellular Lipid Traffic and Lipid Transporters:
Regulation of Efflux and HDL Formation 73
Yves L. Marcel, Mireille Ouimet, and Ming-Dong Wang
3.1 Introduction 73
3.2 Regulation of apoA-I Synthesis, Lipidation and Secretion
in Hepatocytes: Genesis of apoA-I-Containing
Lipoproteins and HDL 74
3.3 Cell Specificity of ABC A1 Expression and HDL
Formation in Vivo: Insight from Genetically Modified Mice 75
3.4 Transcriptional and Posttranscriptional Regulation of ABC A1 76
3.5 Cellular Traffic of ABCA1 78
3.5.1 Syntrophin and the Regulation of Lipid
Efflux Activity 78
3.5.2 Sorting of ABCA1 Between Golgi, Plasma
Membrane and LE-Lysosomes: Contribution of Sortilin 81
3.6 Integrated Models of Lipid Efflux and Lipoprotein Assembly:
Nascent HDL Formation 82
3.6.1 Interaction of apoA-I with Cell Surface ABCA1 83
Contents ix
3.6.2 Contribution of Retroendocytosis 84
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 85
3.7.1 HDL Genesis in Various Types of Cells 85
3.7.2 Cholesterol Efflux to apoA-I in Macrophages 86
3.7.3 In Vivo Cholesterol Efflux from Macrophages
and Reverse Cholesterol Transport 87
3.8 Cellular Lipid Traffic Through the Late Endosomes 88
3.8.1 Egress of Cholesterol From LE 88
3.8.2 Regulation of Cholesterol Traffic in LE 89
3.9 Cholesterol Traffic Through the Lipid Droplet 91
3.9.1 Regulation of Cholesterol Traffic in the Adipocyte LD 92
3.9.2 Regulation of Cholesterol Traffic in the Macrophage LD... 92
3.9.3 Regulation of Cholesterol Traffic in the Hepatocyte LD 93
3.10 Caveolin and Cellular Cholesterol Transport 94
3.11 Mobilization of LD Lipids for Efflux 95
3.11.1 The LD is the Major Source of Cholesterol for Efflux 95
3.11.2 Hydrolysis and Mobilization of LD Cholesteryl
Esters for Efflux 96
3.11.3 Is ABCA 1 Involved in the Mobilization and Traffic
of LD Cholesterol for Efflux? 97
3.12 Conclusions 97
References 98
4 Bile Acids and Their Role in Cholesterol Homeostasis 107
Nora Bijl, Astrid van der Velde, and Albert K. Groen
4.1 Introduction 107
4.2 Bile Acid Synthesis 108
4.2.1 Regulation of Synthesis by Nuclear Receptors 109
4.2.2 Oxysterol Feed-Forward Regulation of Bile Synthesis 110
4.2.3 Bile Acid Feedback Regulation of Bile Synthesis 110
4.2.4 FGF-Regulated Feedback of Bile Synthesis 111
4.2.5 Other Pathways 113
4.3 Regulation of the Enterohepatic Circulation 115
4.3.1 Liver 115
4.3.2 Intestine 117
4.4 Cholesterol in the Enterohepatic Circulation 117
4.4.1 Cholesterol Absorption in the Intestine 118
4.4.2 Intestinal Cholesterol Secretion 119
4.4.3 Novel Pathways for Cholesterol Excretion 120
4.5 Role of the Enterohepatic Cycle in the Control
of Cholesterol Homeostasis 123
4.6 Concluding Remarks 124
References 124
x Contents
5 Cholesterol Trafficking in the Brain 131
Dieter Liitjohann, Tim Vanmierlo, and Monique Mulder
5.1 Introduction 131
5.2 Cholesterol Turnover in the Brain 132
5.3 Release of 24(5)-Hydroxycholesterol from the Brain
into the Circulation 135
5.4 Lipoproteins in the Cerebrospinal Fluid 136
5.5 Astrocytes Supply Neurons with Cholesterol 137
5.6 How do Neurons Regulate Their Cholesterol Supply? 139
5.7 Alternative Pathway for Cholesterol Release from Neurons? 142
5.8 Role for cAMP Responsive Element Binding Protein
in the Regulation of Neuronal Cholesterol Homeostasis 143
5.9 Internalization of Cholesterol by Neurons 143
5.10 The Choroid Plexus as an Alternative Source of HDL 144
5.11 Disturbances in Cholesterol Trafficking Between Astrocytes
and Neurons in Alzheimer s Disease? 145
5.12 Do Alterations in Systemic Sterol Metabolism Alter Brain
Sterol Metabolism? 147
References 148
6 Intracellular Cholesterol Transport 157
Daniel Wiistner
6.1 Biophysical Properties of Cholesterol in Model Membranes 157
6.2 Molecular Organization and Function of Cholesterol
in the Plasma Membrane 161
6.3 Overview of Membrane Traffic Along the Endocytic
and Secretory Pathways and its Dependence on Cholesterol 165
6.4 Function of Various Organelles in Cellular
Cholesterol Metabolism and Transport 168
6.5 Vesicular and Non-Vesicular Transport of Cholesterol:
Targets, Kinetics and Regulation 171
6.6 Alterations in Intracellular Cholesterol Trafficking
in Atherosclerosis and Lipid Storage Diseases 176
6.7 Future Prospects 180
References 181
7 Role of the Endothelium in Lipoprotein Metabolism 191
Arnold von Eckardstein and Lucia Rohrer
7.1 Introduction 191
7.2 Expression of Proteins Involved in Lipoprotein Metabolism 192
7.2.1 Lipoprotein Lipase andGPIHBPl 193
7.2.2 Hepatic Lipase 193
7.2.3 Endothelial Lipase 194
7.3 Lipoprotein Transport Through the Endothelium 195
Contents xi
7.3.1 General Aspects of Transendothelial
Lipoprotein Transport 195
7.3.2 Paracellular (Lipo)protein Transport 196
7.3.3 Transendothelial (Lipo)protein Transport 198
7.4 Target for Physiological and Pathological Effects
of Lipoproteins 200
7.4.1 Regulation of the Vascular Tone 200
7.4.2 Leukocyte Adhesion and Extravasation 202
7.4.3 Platelet Aggregation, Coagulation, and Fibrinolysis 203
7.4.4 Endothelial Survival and Repair 204
References 206
8 Receptor-Mediated Endocytosis and Intracellular
Trafficking of Lipoproteins 213
Joerg Heeren and Ulrike Beisiegel
8.1 Lipoproteins and Their Receptors 213
8.1.1 Metabolism of LDL 214
8.1.2 Metabolism of Triglyceride-Rich Lipoproteins 215
8.2 Receptor-Mediated Endocytosis of LDL 216
8.2.1 Structure and Function of the LDL Receptor 217
8.2.2 Ligands of the LDL Receptor 219
8.2.3 Intracellular Processing of LDL 220
8.2.4 Regulation of LDL Receptor Function 221
8.3 Receptor-Mediated Endocytosis of Chylomicron Remnants 223
8.3.1 Structure and Function of LRP1 223
8.3.2 Ligands of LRP1 224
8.3.3 Intracellular Processing of Chylomicron Remnants 225
8.3.4 Regulation of LRP1 Function 229
References 230
9 Angiopoietin-Like Proteins and Lipid Metabolism 237
Sander Kersten
9.1 Introduction 237
9.2 Angptl4 and Lipid Metabolism 238
9.2.1 Discovery and Structure of Angptl4 238
9.2.2 Regulation of Angptl4 Expression 239
9.2.3 Role of Angptl4 in Lipid Metabolism 240
9.2.4 Role of Angptl4 in Human 243
9.3 Angptl3 and Lipid Metabolism 243
9.3.1 Discovery and Structure of Angptl3 243
9.3.2 Regulation of Angptl3 Expression 244
9.3.3 Role of Angptl3 in Lipid Metabolism 244
9.3.4 Role of Angptl3 in Human 246
9.5 Conclusion 246
References 246
xii Contents
10 Thyroid Hormones and Lipid Metabolism:
Thyromimetics as Anti-Atherosclerotic Agents? 251
Bernhard Foger, Andreas Wehinger, Josef R. Patsch,
Ivan Tancevski, and Andreas Ritsch
10.1 Thyroid Hormones, Thyroid Hormone-Receptors
and Lipoprotein Metabolism 252
10.1.1 Thyroid Hormone Signalling 252
10.1.2 Thyroid Function and Lipoprotein Metabolism 253
10.2 Thyromimetics and Thyromimetic Compounds 268
10.2.1 Background 268
10.2.2 Selective Thyromimetic Compounds 270
10.2.3 Selective Thyromimetics as Hypolipidemic Drugs 271
10.2.4 Potential Additional Applications 273
10.2.5 Off-Target Toxicity of Selective Thyromimetics 274
References 276
11 Adipokines: Regulators of Lipid Metabolism 283
Oreste Gualillo and Francisca Lago
11.1 Introduction 283
11.2 Regulation of Lipid Metabolism by Adipokines 284
11.2.1 Leptin 284
11.2.2 Adiponectin 290
11.2.3 Other Relevant Adipokines Contributing
to Lipid Metabolism 291
11.3 Conclusions 294
References 295
12 Cellular Cholesterol Transport - Microdomains,
Molecular Acceptors and Mechanisms 301
Christopher J. Fielding
12.1 Overview 301
12.2 Structure and Properties of the Cell Surface 304
12.3 Role of Cell-Surface Lipid Transporters in RCT 305
12.4 Cholesterol Efflux and the LCAT Reaction 306
12.5 Significance of ABCG1 308
12.6 Recycling of apo-A-1 308
12.7 RCT from Activated Macrophages 309
References 311
Contents xiii
13 The Ins and Outs of Adipose Tissue 315
Thomas Olivecrona and Gunilla Olivecrona
13.1 Introduction 316
13.2 Sources of Lipids for Deposition in Adipose Tissue 317
13.3 Lipoprotein Lipase 321
13.3.1 Molecular Properties 321
13.3.2 Synthesis, Maturation and Transport of LPL 329
13.3.3 LPL at the Endothelium 336
13.3.4 Regulation/Modulation of Tissue LPL Activity 343
13.4 Intracellular Lipases 347
13.4.1 Adipose Triglyceride Lipase 347
13.4.2 Hormone-Sensitive Lipase 348
13.4.3 Monoacylglycerol Hydrolase 349
13.4.4 Perilipin and the Orchestration of Lipolysis 350
13.5 Triglyceride Synthesis 350
13.5.1 A Triglyceride-Diglyceride Cycle? 351
13.5.2 Reacylation of Monoglycerides 351
13.5.3 De Novo Synthesis of Triglycerides 352
13.5.4 Acylation-Stimulating Protein 352
13.6 Conclusion: an Integrated View of the Lipase Systems
in Adipose Tissue 353
References 354
Index 371
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| spelling | Cellular lipid metabolism Christian Ehnholm (ed.) Berlin [u.a.] Springer 2009 XVIII, 376 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Lipidstoffwechsel - Cytologie - Aufsatzsammlung Lipid Metabolism physiology Lipids Metabolism Lipidstoffwechsel (DE-588)4035875-6 gnd rswk-swf Cytologie (DE-588)4070177-3 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Lipidstoffwechsel (DE-588)4035875-6 s Cytologie (DE-588)4070177-3 s DE-604 b DE-604 Ehnholm, Christian (DE-588)138801789 edt HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017738261&sequence=000004&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Cellular lipid metabolism Lipidstoffwechsel - Cytologie - Aufsatzsammlung Lipid Metabolism physiology Lipids Metabolism Lipidstoffwechsel (DE-588)4035875-6 gnd Cytologie (DE-588)4070177-3 gnd |
| subject_GND | (DE-588)4035875-6 (DE-588)4070177-3 (DE-588)4143413-4 |
| title | Cellular lipid metabolism |
| title_auth | Cellular lipid metabolism |
| title_exact_search | Cellular lipid metabolism |
| title_full | Cellular lipid metabolism Christian Ehnholm (ed.) |
| title_fullStr | Cellular lipid metabolism Christian Ehnholm (ed.) |
| title_full_unstemmed | Cellular lipid metabolism Christian Ehnholm (ed.) |
| title_short | Cellular lipid metabolism |
| title_sort | cellular lipid metabolism |
| topic | Lipidstoffwechsel - Cytologie - Aufsatzsammlung Lipid Metabolism physiology Lipids Metabolism Lipidstoffwechsel (DE-588)4035875-6 gnd Cytologie (DE-588)4070177-3 gnd |
| topic_facet | Lipidstoffwechsel - Cytologie - Aufsatzsammlung Lipid Metabolism physiology Lipids Metabolism Lipidstoffwechsel Cytologie Aufsatzsammlung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017738261&sequence=000004&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT ehnholmchristian cellularlipidmetabolism |