Metabolic Syndrome Pathophysiology: The Role of Essential Fatty Acids

280 Pages·2010·4.76 MB·English

by  Undurti N. Das(auth.)

FM BLBS049-Das December15,2009 9:0 CharCount=
Metabolic Syndrome Pathophysiology
TheRoleofEssentialFattyAcids
Metabolic Syndrome Pathophysiology: The Role of Essential Fatty Acids Undurti N. Das
© 2010 Undurti N. Das ISBN: 978-0-813-81553-4
FM BLBS049-Das December15,2009 9:0 CharCount=
Metabolic Syndrome Pathophysiology
The Role of Essential Fatty Acids
UNDURTI N. DAS, MD, PhD, FAMS
PresidentandCEOofUNDLifeSciences,Ohio
Editor-in-ChiefofLipidsinHealthandDisease
A John Wiley & Sons, Ltd., Publication
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Editionfirstpublished2010
(cid:1)C 2010UndurtiN.Das
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LibraryofCongressCataloging-in-PublicationData
Das,UndurtiN.
Metabolicsyndromepathophysiology:theroleofessentialfattyacids/UndurtiN.Das.
p.;cm.
Includesbibliographicalreferencesandindex.
ISBN-13:978-0-8138-1553-4(alk.paper)
ISBN-10:0-8138-1553-3(alk.paper)
1.Metabolicsyndrome–Pathophysiology. 2.Essentialfattyacids–Pathophysiology. 3.Unsaturatedfatty
acids–Pathophysiology. 4.Insulinresistance–Pathophysiology. 5.Non-insulin-dependent
diabetes–Pathophysiology. 6.Brain–Metabolism. I.Title.
[DNLM:1.MetabolicSyndromeX–physiopathology. 2.Brain–physiopathology. 3.FattyAcids,
Essential–pharmacology. 4.FattyAcids,Essential–physiology. 5.FattyAcids,
Unsaturated–pharmacology. 6.FattyAcids,Unsaturated–physiology.WK820D229m2010]
RC662.4.D372010
616.3(cid:2)99–dc22
2009034624
AcatalogrecordforthisbookisavailablefromtheU.S.LibraryofCongress.
Setin10.5/12ptTimesbyAptara(cid:1)R Inc.,NewDelhi,India
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1 2010
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To
MyWifeLakshmi
and
MyTwoEyes
DaughterArundhatiandSonAditya
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Contents
Preface xiii
1 Introduction 1
2 History,Definition,andDiagnosisoftheMetabolicSyndrome 4
HistoricalAspectsoftheMetabolicSyndrome 4
DefinitionandDiagnosisoftheMetabolicSyndromeSuggestedbyVarious
GroupsandAssociations 5
3 InsulinResistanceintheMetabolicSyndrome 13
IsInsulinResistanceResponsiblefortheMetabolicSyndrome? 13
ExerciseandInsulinResistance 14
Anti-inflammatoryNatureofExercise 15
4 IsItNecessarytoRedefinetheMetabolicSyndrome? 22
Criteria 23
5 IsInsulinResistanceaDisorderoftheBrain? 26
ParasympatheticandSympatheticTonesandInsulinResistance 26
Hypothalamo-pituitary-adrenalPathwayandParasympatheticand
SympatheticSystem,andGLUT-4andHypothalamic
NeuropeptideYinInsulinResistance,Obesity,andthe
MetabolicSyndrome 27
Interaction(s)amongNPY,Leptin,GLUT-4,Melanocortin,andInsulin
andItsRelevancetoObesity,InsulinResistance,andthe
MetabolicSyndrome 29
InsulinandBrain 31
InsulinandBrainMonoamines 34
ObesityandBasalEnergyExpenditure 39
6 Obesity 43
DefinitionofObesity 44
IncidenceandPrevalenceofObesity 44
ObesityCouldRunintheFamily 45
GrowthofFastFoodIndustryandObesity 45
WhyIsObesityHarmful? 46
GeneticsofObesity 47
GeneExpressionProfileinObesity 49
vii
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viii CONTENTS
BiochemicalandFunctionalDifferencesbetweenAdiposeCellsof
DifferentRegions 49
IntramyocellularLipidContentandInsulinResistance 51
IntramyocellularLipidDropletsandInsulinResistance 53
IntramyocellularLipidDroplets,InsulinResistance,Perilipins,andHSL 54
PerilipinsinHumans 55
FactorsRegulatingtheExpressionandActionofPerilipin 56
PerilipinsandInflammation 59
Low-gradeSystemicInflammationOccursinObesity 59
WhatCausesAbdominalObesity? 61
11β-HydroxysteroidDehydrogenaseType1(11β-HSD-1)Enzymeand
Obesity 61
GlucocorticoidsandPerilipins 63
Glucocorticoids,TNF-α,andInflammation 64
Perilipins,11β-HSD-1,andAbdominalObesityandtheMetabolic
SyndromeinHigh-RiskGroupsSuchasSouthAsians 65
7 PerinatalNutritionandObesity 74
AppetiteRegulatoryCentersDevelopduringthePerinatalPeriod 74
VentromedialHypothalamusPlaysaSignificantRoleinthe
DevelopmentofObesity,Type2DiabetesMellitus,andthe
MetabolicSyndrome 76
GlucokinaseinHypothalamicNeuronsandVMHLesioninGoto-Kakizaki
RatsandTheirRelationshiptoObesity,Type2DiabetesMellitus,and
theMetabolicSyndrome 77
InsulinandInsulinReceptorsintheBrainandTheirRoleinthe
PathobiologyofObesity,Type2DiabetesMellitus,andthe
MetabolicSyndrome 78
NPY,Insulin,andNitricOxideinObesity,Type2DiabetesMellitus,and
theMetabolicSyndrome 80
Insulin,EndothelialNitricOxide,andMetabolicSyndrome 81
PerinatalProgrammingofAdultDiseases 81
FetalNutritionInfluencestheDevelopingNeuroendocrineHypothalamus 82
8 EssentialHypertension 86
PrevalenceandIncidenceofHypertension 86
FreeRadicalsinthePathobiologyofHypertension 88
IncreaseinSuperoxideAnionProductioninHypertension:HowandWhy? 89
Mechanism(s)ofInductionofHypertensionbySuperoxideAnion 91
RoleofNOinHypertension 92
Salt,Cyclosporine,andCalciumModulateO −.andEndothelialNO
2
Generation 94
l-Arginine,NO,andAsymmetricalDimethylarginineinHypertension
andPre-eclampsia 95
AntihypertensiveDrugsSuppressSuperoxideAnionandEnhanceNO
Generation 97
TransformingGrowthFactor-β,NO,andHypertension 97
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CONTENTS ix
9 DietaryFactorsandHypertension 105
Carbohydrate-richandHigh-fatDietandHypertension 105
Fructose-inducedHypertensionandInsulinResistanceand
ItsModulationbyDietarySalt 106
Energy-denseDiet,Salt,andHypertension 106
Diet-inducedHypertension,Renin-Angiotensin-AldosteroneSystem,
andNitricOxide 107
High-sugarandHigh-fat-inducedHypertensionandReactiveOxygen
SpeciesandNitricOxide 108
High-fructoseandSalt-inducedHypertensionandInsulinResistance 109
High-fatandHigh-carbohydrate-inducedHypertensionand
SympatheticNervousActivity 111
10 IsHypertensionaDisorderoftheBrain? 113
NOSynthase(NOS)ActivityintheBrain,Kidney,andEndotheliumand
ItsRelationshiptoHypertension 114
ReducedHypothalamicNOSProducesHypertensionwithoutAltering
HypothalamicBloodFlow 115
HypothalamicNORegulatesSympatheticOutflow 116
Steroid-inducedHypertensionandHypothalamus 117
ExerciseEnhancesHypothalamicNOSActivity 119
BothHypertensionandType2DiabetesMellitusandHencetheMetabolic
SyndromeAreDisordersoftheBrain 119
11 Type2DiabetesMellitus 122
Type1DiabetesMellitus 122
PathobiologyofType1Diabetes 123
Type2DiabetesMellitus 125
DiagnosticCriteriaforDM 126
ImpairedGlucoseToleranceandImpairedFastingGlucose 127
DefinitionofGestationalDiabetesMellitus 127
DiagnosticCriteriaforGDM 127
12 PathophysiologyofType2DiabetesMellituswithParticular
ReferencetoHypothalamus 130
Type2DiabetesMellitusasaDisorderoftheBrain 130
LiverCommunicateswiththeBrainthroughtheVagus 131
LiverandPancreaticβ CellsCommunicatewithEachOtherthrough
theVagus 132
TheGut-brain-liverAxisIsActivatedbyLong-chainFattyAcids
(LCFAsorLCPUFAs) 132
BDNFandObesity 136
BDNFandType2DiabetesMellitusinHumans 137
Insulin,Melanocortin,andBDNF 138
Ghrelin,Leptin,andBDNF 138
Low-gradeSystemicInflammationOccursinObesityandType2
DiabetesMellitus 140
BDNFandInflammation 141
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x CONTENTS
13 InsulinandInsulinReceptorsintheBrainandTheirRoleinthe
PathogenesisofObesityandType2DiabetesMellitus 146
InsulinandInsulinReceptorsintheBrain 146
GlucoseTransportersandGlucokinaseinHypothalamus 147
Neuron-specificDisruptionoftheInsulinReceptorGene(NIRKO) 147
InsulinandHypothalamicNeuropeptides 148
LeptinReceptorsonPancreaticβ Cells 148
Glucagon-likePeptide,Insulin,andtheMetabolicSyndrome 149
14 Insulin,EndothelialNitricOxide,and
theMetabolicSyndrome 156
InsulinResistanceandNitricOxide 156
GhrelinImprovesEndothelialFunctionintheMetabolicSyndrome 159
Cross-talkbetweenInsulinandRenin-Angiotensin-AldosteroneSystem 159
Pro-inflammatoryCytokinesProduceInsulinResistance 161
15 Obesity,Type2DiabetesMellitus,theMetabolicSyndrome,andthe
GutMicrobiota 167
GutFlora,Diet,Obesity,andInflammation 167
Germ-freeMiceAreResistanttoObesity 168
EnteroendocrineCellExpressionofGpr41andObesity 169
Low-gradeSystemicInflammation,Diet,andObesity 171
GastricBypassSurgeryforObesityandtheMetabolicSyndrome 171
Diet,Gut,Liver,AdiposeTissue,andHypothalamusinObesityand
theMetabolicSyndrome 173
16 IsItPossibleThattheMetabolicSyndromeOriginatesinthe
PerinatalPeriod? 177
PerinatalProgrammingofAppetiteRegulatoryCentersand
HypothalamicCenters 177
InsulinandInsulinReceptorsintheBrain 178
17 EssentialFattyAcids:BiochemistryandPhysiology 181
MetabolismofEFAs 181
DietarySourcesofEFAs 183
ModulatorsofMetabolismofEFAs 183
PUFAsandSREBPs 184
Cholesterol,SaturatedFats,andTrans-fatsInterferewiththeActivityof(cid:3)6
and(cid:3)5Desaturases 185
ActionsofEFAsandTheirMetabolites 188
BriefDescriptionofFormationofLipoxins,Resolvins,NeuroprotectinD1
(Protectins),andMaresins 193
Nitrolipids 194
18 RoleofEFAs/PUFAsinBrainGrowthandDevelopmentand
PathophysiologyoftheMetabolicSyndrome 201
PUFAsinBrainGrowthandDevelopment 201
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CONTENTS xi
RAR-RXRNuclearReceptors,PUFAs,andNeuronalGrowth 202
InteractionamongTNF-α,AA/EPA/DHA,andInsulinandTheirRolein
NeuronalGrowthandSynapseFormation 202
PUFAsandCatenin,wnt,andHedgehogSignalingPathwayinBrain
GrowthandDevelopment 203
β-Catenin-WntSignalingandPUFAs 205
ModulationoftheSecretionandFunctionofNMDA,γ-Aminobutyric
Acid(GABA),Serotonin,andDopaminebyPUFAs 205
LeptinRegulatesNPY/AgRPandPOMC/CARTNeuronsandPrograms
Hypothalamic“BodyWeight/Appetite/SatietySetPoint” 209
PUFAsRegulateLeptin,NPY/AgRP,andPOMC/CARTNeuronsand
ParticipateinProgrammingHypothalamic“BodyWeight/
Appetite/SatietySetPoint” 212
PUFAs,Insulin,andAcetylcholineNotOnlyInteractamongThemselves
butAreAlsoNeuroprotectiveinNature 215
PUFAsandInsulinResistance 215
MaternalDietInfluencesδ(cid:3)6andδ(cid:3)5DesaturasesandLeptinLevels 216
Interaction(s)amongHypothalamicNeuropeptides,Gut,AdiposeTissue,
Insulin,Cytokines,andFreeRadicalsandItsRelevancetothe
PathophysiologyoftheMetabolicSyndrome 217
HypothalamicGeneExpressionProfileintheRYGBAnimalModel 218
IncreasedPhospholipaseA ExpressionafterRYGBSurgery
2
andItsRelevancetoSuppressionofLow-gradeSystemic
InflammationintheObeseandFormationofAnti-inflammatory
Lipids 219
ExpressionofGeneforeNOSinRYGB 220
RYGB-inducedWeightLossIsDuetoChangesintheLevelsof
HypothalamicNeuropeptidesandMonoamines 220
WhatAretheDiagnosticandPrognosticImplicationsofThisKnowledge? 221
TherapeuticImplications 223
PUFAsandEndocannabinoids 224
PUFAsandType2DiabetesMellitus 224
HypothalamicPUFAsRegulateInsulinSecretionandGlucoseHomeostasis
byInfluencingATP-sensitiveK+Channels 225
VagusastheCommunicatorbetweenGut,Liver,andHypothalamus 227
19 EFAs/PUFAsandTheirMetabolitesinInsulinResistance 240
GLUT-4inInsulinResistance 240
TumorNecrosisFactorInducesInsulinResistance 242
CaloricRestrictionInfluencesInsulinSignalingPathway,Antioxidants,daf
genes,PTEN,Sirtuins(SilentMatingTypeInformationRegulation2
Homologue),andLongevityandTheirRelationshiptoInsulinResistance 242
PUFAsCanReduceInsulinResistance 244
PUFAs,GLUT-4,TNF-α,Anti-oxidants,dafGenes,SIRT1,andPPARs 245
ClinicalImplicationsoftheInteractionsamongPUFAs,dafGenes,PPARs,
andSirtuins 246
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xii CONTENTS
20 EFAs/PUFAsandAtherosclerosis 252
AtherosclerosisIsaSystemicInflammatoryCondition 252
Cross-talkamongPlatelets,Leukocytes,andEndothelialCells 253
LeukocytesandAtherosclerosis 254
EFAsModulateUncouplingProtein-1Expression 255
Interaction(s)amongω-3andω-6FattyAcidsandTrans-fatsand
SaturatedFats 255
AtheroprotectiveActionsofω-3andω-6FattyAcids:HowandWhy? 259
Index 265