Adipose Tissue in Health and Disease

513 Pages·2010·4.421 MB·English

Edited by
Todd Leff and
James G. Granneman
Adipose Tissue in
Health and Disease
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Edited by
Todd Leff and James G. Granneman
Adipose Tissue in Health and Disease
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V
Contents
Preface XIX
List of Contributors XXI
PartOne AdiposeTissueDevelopmentandMorphology 1
1 TranscriptionalControlofAdipogenesisandFatCellGeneExpression 3
UrsulaA.WhiteandJacquelineM.Stephens
1.1 Introduction 3
1.2 TranscriptionalControlofAdipogenesis 4
1.2.1 AP-1TranscriptionFactors 4
1.2.2 SignalTransducersandActivatorsofTranscription 5
1.2.3 Krüppel-LikeFactors 6
1.2.4 SREBPs 7
1.2.5 C/EBP 7
1.2.6 PPAR-c 8
1.3 IdentificationofAdipocyteTranscriptionFactorTargetGenes 9
1.3.1 C/EBPTargetGenes 9
1.3.2 SREBP-1TargetGenes 10
1.3.3 PPAR-cTargetGenes 11
1.3.4 STAT-5TargetGenes 12
1.3.5 Summary 13
References 14
2 CellularandMolecularBasisofFunctionalDifferencesamong
FatDepots 21
ThomasThomou,TamaraTchkonia,andJamesL.Kirkland
2.1 Introduction 21
2.1.1 FatTissueFunction 21
2.1.2 DiversityinFatDistribution 23
2.1.3 RegionalDifferencesinFatTissueGrowth 24
2.1.4 DiseaseAssociations 26
2.2 Physiology 27
AdiposeTissueinHealthandDisease.EditedbyToddLeffandJamesG.Granneman
Copyright(cid:1)2010WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:978-3-527-31857-5
VI Contents
2.2.1 ContributionofInherentCellDynamicMechanismstoRegional
Differences 28
2.2.2 PreadipocyteFunction 29
2.2.3 PreadipocyteReplication 29
2.2.4 DifferencesinAdipogenesisamongDepots 30
2.2.5 RegionalVariationinSusceptibilitytoApoptosis 32
2.2.6 DifferencesinPreadipocyteSubpopulationsamongFatDepots 32
2.2.7 DifferencesinPreadipocyteGeneExpressionProfiles
amongDepots 33
2.3 Conclusions 35
References 36
3 PlasticityoftheAdiposeOrgan 49
SaverioCinti
3.1 Introduction 49
3.2 GrossAnatomyDemonstratesthatWATandBATareMixedTogether
intheAdiposeOrgan 50
3.3 LightandElectronMicroscopyshowthatWhiteandBrownAdipocytes
haveaWell-DefinedandDistinctMorphology 51
3.3.1 WAT 51
3.3.2 BAT 52
3.4 WATandBAThaveaDifferentVascularandNerve
Supply 53
3.5 WATandBAThaveaDifferentPhysiology 54
3.6 PhenotypeoftheAdiposeOrganisVariable:Plasticityofthe
AdiposeOrgan 55
3.6.1 TransformationofthePhenotype:ColdandWarmExposure
andAcclimatization 55
3.6.2 TransformationofthePhenotype:PregnancyandLactation 58
3.6.3 TransformationofthePhenotype:Hypertrophyand
Hyperplasia(PositiveEnergyBalance:Overweight
andObesity) 59
3.6.4 TransformationofthePhenotype:Hypoplasia(NegativeEnergy
Balance:CaloricRestrictionandFasting) 60
3.7 AdiposeOrganofHumans 61
References 63
4 BiologyofAdiposeTissueStemCells 69
JeffreyM.Gimble,BruceA.Bunnell,andFarshidGuilak
4.1 Introduction 69
4.2 InSituLocalizationandEmbryology 69
4.3 IsolationMethods 70
4.3.1 Yield,ProliferationRate,Depot,andAgingInfluences 70
4.4 Characterization 71
4.4.1 Immunophenotype 71
Contents VII
4.4.2 Immunogenicity 71
4.4.3 ProteomicandTranscriptomicAnalysis 72
4.4.4 CytokineProfile 72
4.4.5 Clonality 72
4.5 DifferentiationandPotentialUtilityforRegenerativeMedicine 73
4.5.1 MesodermalLineages 73
4.5.2 EndodermalandEctodermalLineages 73
4.6 Conclusions 74
References 74
PartTwo MetabolicFunctionsofAdiposeTissue 81
5 MolecularMechanismsofAdipocyteLipolysis 83
JamesG.GrannemanandHsiao-PingH.Moore
5.1 Introduction 83
5.2 KeyPlayersinAdipocyteLipolysis 83
5.2.1 LipidDropletsandDropletScaffoldProteins 84
5.2.2 Lipases 86
5.2.2.1 HSL 86
5.2.2.2 AdiposeTriglycerideLipase 87
5.2.2.3 CGI-58 87
5.2.2.4 OtherLipasesandtheBiologicalSignificanceofHSL
versusATGL 88
5.3 LipolyticProteinTrafficking 88
5.3.1 PLINSubcellularTargeting 88
5.3.2 InteractionswithCGI-58 88
5.3.3 InteractionswithHSL 89
5.3.4 InteractionswithATGL 89
5.3.5 DisruptionandDispersionofLipidDropletsFollowing
PKAActivation 90
5.3.6 AdditionalInteractions 90
5.4 WorkingModelandUnresolvedIssues 91
References 93
6 NewDevelopmentsintheLipolyticProcessing
ofTriglyceride-RichLipoproteins 97
AndréBensadoun,AnneP.Beigneux,LorenG.Fong,
andStephenG.Young
6.1 Introduction 97
6.2 LPL 98
6.3 FunctionalDomainsofLPL 99
6.4 RegulationofLPLActivitybyAngiopoietin-LikeProteins 100
6.5 RoleofGPIHBP1intheLipolysisofTriglyceride-Rich
Lipoproteins 101
6.6 RoleofApo-AVinLipolysis 103
VIII Contents
6.7 NewlyDiscoveredRegulatorsofLPLActivityandtheir
PhysiologicalSignificance 104
References 105
7 IntracellularFattyAcidTransport,Activation,andTrafficking 109
DougMashek
7.1 Introduction 109
7.2 FattyAcid-BindingProteinFamily 109
7.2.1 FunctionandRegulationofFABP-4 110
7.2.2 FunctionandRegulationofFABP-5 112
7.3 FattyAcidActivationandChanneling:RoleofLong-Chain
Acyl-CoASynthetasesandFattyAcidTransportProteins 113
7.4 RoleofAcyl-CoA-BindingProteininAcyl-CoA
Metabolism 116
7.5 RegulationandFunctionofDistinctFattyAcidand
Acyl-CoAPools 117
7.6 ContributionofFattyAcidandAcyl-CoAMetabolism
toMetabolicDiseases 119
7.7 Conclusions 121
References 121
8 AquaporinsandAdiposeTissue:LessonfromDiscovery
toPhysiopathologyandtotheClinicofAquaporin
Adipose(AQP7) 129
KenKishida
8.1 Introduction 129
8.2 CharacteristicsofAdipocytesandGycerolMetabolisminthe
MammalianBody 130
8.3 AdiposeGlycerolChannel:AQP7 132
8.3.1 AQP7:APutativeAdipose-SpecificGlycerolChannel 132
8.3.2 FunctionandRegulationofAQP7inAdipocytes 134
8.3.3 HumanAQP7GeneticMutation 137
8.3.4 Adipose-DerivedGlycerolandGluconeogenesis
throughAQP7–LessonsfromAQP7-DeficientMice
andCells 139
8.4 HepaticGlycerolChannel:AQP9 141
8.4.1 AQP9:APutativeHepatic-SpecificGlycerolChannel 141
8.4.2 GluconeogenesisthroughAQP9–Lessonsfrom
AQP9-DeficientMice 142
8.5 CoordinationofAdiposeGlycerolChannel,AQP7,
andHepaticGlycerolChannel,AQP9 143
8.6 DysregulationofAQP7andAQP9inObesitywith
InsulinResistance 143
8.7 Conclusions 144
References 144
Contents IX
9 SignalingPathwaysControllingLipolysisandLipid
MobilizationinHumans 149
MaxLafontan
9.1 Introduction 149
9.2 RoleofLipasesintheRegulationofHydrolysisofFatCell
Triacylglycerols 151
9.2.1 Hormone-SensitiveLipase 151
9.2.2 AdiposeTissueTriglycerideLipase 151
9.3 AdrenergicControlofcAMPProduction,Lipolysis
andLipidMobilization 152
9.4 ControlofcAMPProductionbyAdenylylCyclase
Inhibitors–InhibitionofLipolysis 157
9.5 Insulin:AMajorAntilipolyticAgentControlling
cAMPDegradation 158
9.6 NatriureticPeptidesControlcGMPProduction,Lipolysis,
andLipidMobilizationinHumans 159
9.6.1 NatriureticPeptides 159
9.6.2 LipolyticEffectofNatriureticPeptides 160
9.6.3 InductionofLipidMobilizationbyAdministration
ofPharmacologicalDosesofANP 162
9.6.4 ContributionofANPtothePhysiologicalControl
ofLipidMobilizationinHumans 162
9.7 OtherLipolyticPathways 163
9.7.1 GrowthHormone 163
9.7.2 IL-6 164
9.7.3 TNF-a 165
9.7.4 OtherLipolyticPeptides 166
9.8 FutureTrendsandPharmacologicalProspects 167
References 168
PartThree EndocrineFunctionsofAdiposeTissue 181
10 LeptinSecretionandAction 183
RobertV.Considine
10.1 Introduction 183
10.2 LeptinSynthesis 184
10.2.1 GenderandBodyFatDistributionDetermineSerumLeptin 184
10.2.2 CaloricIntake,Insulin,andGlucoseInfluenceSerumLeptin 185
10.2.3 TranscriptionalRegulationofLeptinSynthesisinAdipocytes 186
10.3 LeptinReceptors 187
10.4 LeptinActionintheCentralNervousSystem 187
10.5 LeptinResistanceinObesity 189
10.6 MetabolicComplicationsofHyperleptinemiainObesity 190
10.6.1 LeptinandObesity-RelatedHypertension 190
10.6.2 OtherPossiblePathologicEffectsofLeptin 191
X Contents
10.7 LeptinTherapyinHumans 192
10.7.1 Leptin,WeightLoss,andHumanObesity 192
10.7.2 CongenitalLeptinDeficiency 192
10.7.3 LipodystrophicLeptinDeficiency 193
10.7.4 HypothalamicAmenorrhea 193
10.8 Conclusions 194
References 194
11 Adiponectin 201
JonathanP.WhiteheadandAyanthiA.Richards
11.1 Introduction 201
11.2 AdiponectinStructureandPost-TranslationalModifications 202
11.3 SignificanceandBioactivityofAdiponectinMultimers 204
11.4 AdiponectinandLiver 205
11.5 AdiponectinandSkeletalMuscle 206
11.6 AdiponectinandtheVasculature 206
11.7 AdiponectinandtheBrain 207
11.8 AdiponectinExpressionandSecretion 208
11.9 AdiponectinSecretion 209
11.10 EctopicAdiponectinExpression 211
11.11 RegulationofExpressionandSecretion 212
11.11.1 Oxidativestress 212
11.11.2 ActivatorsofPPARc–TZDsandFishOils 213
11.11.3 WeightLoss 213
11.11.4 OtherAgents 214
11.12 AdiponectinClearance 214
11.13 AdiponectinReceptorsandDownstreamEffectors 215
11.14 AdiponectinSignaling 216
11.15 Conclusions 217
References 218
12 Preadipocytefactor-1andAdiposeTissue-SpecificSecretory
Factor/Resistin–TwoSecretedFactorsfromAdiposeTissue:
RoleinAdipogenesisandInsulinResistance 231
HeiSookSul,YuhuiWang,andCarolynHudak
12.1 Introduction 231
12.2 Pref-1Structure 232
12.3 Pref-1InhibitionofAdipocyteDifferentiation 233
12.4 MechanismforPref-1Function 234
12.5 InVivoEffectofPref-1onAdipogenesisandGlucose/Insulin
Homeostasis 235
12.6 ADSF/Resistin:IdentificationandStructure 236
12.7 ADSF/ResistinExpressionandFunction 237
12.8 Conclusions 239
References 240