Beneficial Effects of Fish Oil on Human Brain

409 Pages·2009·10.03 MB·English

by  Akhlaq Farooqui (auth.)

Beneficial Effects of Fish Oil on Human Brain
Akhlaq A. Farooqui
Beneficial Effects of Fish
Oil on Human Brain
1 3
AkhlaqA.Farooqui
DepartmentofMolecular
andCellularBiochemistry
TheOhioStateUniversity
Columbus,OH43221
USA
[email protected]
ISBN978-1-4419-0542-0 e-ISBN978-1-4419-0543-7
DOI10.1007/978-1-4419-0543-7
SpringerDordrechtHeidelbergLondonNewYork
LibraryofCongressControlNumber:2009929747
#SpringerScienceþBusinessMedia,LLC2009
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In the memory of my beloved uncle ‘‘late
Mohd Ateeq Saheb’’ and grandmother ‘‘late
Masoodi Begum,’’ who brought me up, gave
me their unyielding support, and taught me
the difference between right and wrong.
– Akhlaq A. Farooqui
Preface
In neural membrane glycerophospholipids, essential polyunsaturated fatty
acids, namely arachidonic acid (ARA) and docosahexaenoicacid (DHA), are
exclusivelylocatedatthesn-2positionofglycerolmoiety.Becausehumansdo
notpossessdesaturasesthatinserteitherthen-3orthen-6doublebonds,these
fattyacidsarederivedfromdiet.DHAcanbeobtainedfromfishorfromthe
precursor a-linolenic acid (ALA), which is found in nuts. The common pre-
cursorforARAisdietarylinoleicacid(LA)fromplantsources.Thehighintake
of food enriched in vegetable oils elevates levels of ARA-derived eicosanoids
and upregulates the expression of proinflammatory cytokines. ARA-derived
eicosanoidshaveprothrombotic,proaggregatory,andproinflammatoryprop-
erties. In contrast, a diet enriched in eicosapentaenoic acid (EPA) and DHA
(fishandfish oil)generatesdocosanoids,which notonlydownregulateproin-
flammatorycytokinesbutalsohaveantiinflammatory,antithrombotic,antiar-
rhythmic, hypolipidemic,and vasodilatory effects. Thus, levelsof eicosanoids
anddocosanoidsinneuralandnon-neuraltissuesarepartlyregulatedbydiet.
ThepresentWesterndietisdeficientinDHA,buthashighamountsofARA.
Thedeficiencyofn–3fattyacidsindietresultsinanumberofabnormalitiesin
animals and human infants such as impaired vision, abnormal electroretino-
gram,andseveralbehavioralabnormalities.Inaddition,inclusionofn–3fatty
acids in diet not only prevents cardiovascular disease but also protects from
stroke,epilepsy,andotherneurologicalandneurodegenerativediseasessuchas
Alzheimerdisease,Parkinsondisease,andperoxisomaldiseases.
TherehavebeenremarkabledevelopmentsonDHAandARAmetabolism
in brain in the past 20 years. The main objective of this book is to present
readerswithcutting-edgeandcomprehensive informationonmetabolismand
rolesofneuralmembraneDHAinamannerthatisusefulnotonlytostudents
and teachers but also to researchers, dietitians, nutritionists, and physicians.
Thismonographhas11chapters.Chapters1and2describetheimportanceof
fish oil inhuman diet alongwithtransportandimportance ofDHA inbrain.
Chapters3and4describecutting-edgeinformationonthereleaseandcatabo-
lism of DHA in brain along with neurochemical effects of its lipid mediators.
Chapter5describesrolesofDHAinbrain.Chapter6isdevotedtoalterations
inDHAwithagingandconsequencesofDHAdeficiencyinbrain.Chapters7
vii
viii Preface
and8describethestatusandtherapeuticimportanceofDHAandEPAinacute
metabolic trauma (stroke), neurotraumatic disorders (spinal cord and head
injuries), and neurodegenerative diseases (Alzheimer disease, Parkinson dis-
ease, Huntington disease). Chapter 9 describes the status and therapeutic
importance of DHA and EPA in neuropsychiatric disorders (schizophrenia,
depression, bipolar disorders, and attention-deficit/hyperactivity disorder).
Chapter 10 provides information on the importance of DHA and EPA in
other neural (peroxisomal) and some non-neural (rheumatoid arthritis, cystic
fibrosis, chronic obstructive pulmonary disease, dermatological conditions,
and gastrointestinal disorders) diseases. Finally, Chapter 11 provides readers
andresearcherswithperspectivethatwillbeimportantforfutureresearchwork
onDHAandEPAinbraintissue.
This monograph can be used as supplemental text for a range of neu-
roscience and nutrition courses. Neurologists and nutritionists will find this
bookusefulforunderstandingmolecularaspectsofDHAandEPAmetabolism
in neurological disorders. To the best of my knowledge, no one has written a
monograph on the role of DHA and EPA and their lipid mediators (docosa-
noids)inbraintissue,andthismonographisthefirsttoprovideacomprehen-
sive description of docosanoids and their interactions with ARA-derived
eicosanoidsinnormalbrainandinbraintissuefrompatientswithneurological
disorders.Thismonographnotonlyprovidesbackgroundandrefresherinfor-
mation on DHA metabolism in brain for readers not working in the field of
fattyacidmetabolismbutalsopresentsnewknowledgeonDHA-derivedlipid
mediators and therefore broadens our understanding of DHA function in
health and neurological disorders. The monograph offers a thorough and
unique overview of the neurobiology of n–3 and n–6 fatty acids and their
associationwithneurologicaldisorders.Itisanticipatedthatnutritionistsand
clinicians maygaininsightintoproblemsassociatedwithnutritioninthe21st
century and resolve difficulties experienced in their research on fatty acid
metabolismandDHA-andARA-derivedlipidmediatorsintheirlaboratories.
Thechoiceoftopicspresentedinthismonographispersonal.Itisbasednot
onlyonmyinterestinDHAandARAmetabolisminneurologicaldisordersbut
also in areas where major progress has been made. I have tried to ensure
uniformity in mode of presentation as well as a logical progression of subject
from one topic to another and have provided extensive bibliography. For the
sakeofsimplicityanduniformity,alargenumberoffiguresandlinediagrams
of signal transduction pathways are also included. I hope that my attempt to
integrateandconsolidatetheknowledgeofDHAmetabolismandsignaltrans-
ductionprocessesinnormalanddiseasedbrainwillprovidethebasisofmore
dramatic advances and developments on the determination, characterization,
androlesofDHA-andARA-derivedlipidmediatorsinneurologicaldisorders.
AkhlaqA.Farooqui
Columbus,Ohio
Acknowledgments
Ithankmywife,Tahira,forcriticalreadingofthismonograph,offeringvalu-
ableadvice,andevaluationofsubjectmatter.Withoutherhelpandparticipa-
tion, this monograph neither could nor would have been completed. I also
thank my son, Siraj, for drawing chemical structures of lipid mediators and
signaltransductionpathwaysassociatedwitharachidonicacidanddocosahex-
aenoic acid metabolism. I would also like to express my gratitude to Ann H.
Avouris of Springer, New York, for her able and professional manuscript
handling.
AkhlaqA.Farooqui
ix
Contents
1 FishOilandImportanceofItsIngredientsinHumanDiet......... 1
1.1 Introduction....................................... 1
1.2 n–3FattyAcidsinFishOilCapsulesandKrillOil
Capliques ......................................... 3
1.2.1 AvailabilityofPurifiedFishOilandKrillOil
Preparations.................................. 4
1.2.2 Othern–3-EnrichedManufacturedProducts ........ 8
1.3 EffectsofFishOilonHumanHealth ................... 8
1.4 EffectsofFishOilonHeart........................... 9
1.4.1 AntiinflammatoryandAntiatheroscleroticEffects
ofFishOil ................................... 10
1.4.2 AntiarrythmicEffectsofFishOil ................. 11
1.4.3 AntithromboticEffectsofFishOil................ 13
1.4.4 Effectofn–3FattyAcidsonRevascularization ...... 14
1.4.5 n–3or!–3IndexandHeartDisease .............. 15
1.5 EffectsofFishOilonBrain ........................... 16
1.5.1 EffectofFishOilonNeuralMembranes ........... 16
1.5.2 EffectofFishOilonNeuritogenesis............... 17
1.5.3 Effectofn–3FattyAcidsonIonChannels.......... 17
1.5.4 Effectofn–3FattyAcidsonReceptors ............ 18
1.6 EffectsofFishOilonLungs........................... 18
1.7 EffectsofFishOilonKidneys......................... 19
1.8 EffectsofFishOilonPlasmaLipids .................... 20
1.9 EffectofFishOilonLiver............................ 22
1.10 n–3FattyAcidsandBleedingTendency ................. 24
1.11 Effectofn–3FattyAcidsonBloodPressure.............. 24
1.12 RecommendationsforIntakeofn(cid:2)3FattyAcids.......... 25
1.13 BeneficialEffectsofOliveOilonHumanHealth .......... 25
1.13.1 EffectsofOliveOilonHeart.................... 25
1.13.2 EffectsofOliveOilonBrain.................... 29
1.14 HarmfulEffectsofTransFattyAcidsonHumanHealth.... 31
1.15 Conclusion ........................................ 34
References.............................................. 35
xi
xii Contents
2 Transport,Synthesis,andIncorporationofn–3andn–6FattyAcids
inBrainGlycerophospholipids .............................. 47
2.1 Introduction....................................... 47
2.2 TransportofDietaryARAandDHAtoBrain............ 48
2.3 ImportanceofDHAinNeuralMembranes............... 51
2.4 ARAandItsImportanceinNeuralMembranes........... 53
2.5 Biosynthesisofn–3andn–6FattyAcidsinLiver .......... 54
2.5.1 Biosynthesisofn–3FattyAcidsinLiver............ 55
2.5.2 Biosynthesisofn–6FattyAcidsinLiver............ 58
2.6 IncorporationofFattyAcidsinGlycerophospholipids...... 60
2.6.1 Acyl-CoASynthetasesinBrain................... 61
2.6.2 Acyl-CoA:lysophospholipidAcyltransferase
inBrain ..................................... 64
2.6.3 CoA-IndependentReacylationinBrain ............ 67
2.7 IncorporationofALAandLAinBrainLipids............ 67
2.8 IncorporationofDocosahexaenoicAcidinNeuralMembranes
inGlycerophospholipids ............................. 68
2.9 IncorporationofArachidonicAcidinNeuralMembranes... 70
2.10 Conclusion ........................................ 70
References.............................................. 71
3 Releaseofn–3andn–6FattyAcidsfromGlycerophospholipids
inBrain ............................................... 79
3.1 Introduction....................................... 79
3.2 ReleaseofDHAfromEthanolamineorCholine
Plasmalogen ....................................... 80
3.2.1 Plasmalogen-Selective-PhospholipaseA inBrain .... 81
2
3.2.2 CanineMyocardiumPlsCho-PLA ................ 88
2
3.2.3 PlsEtn-PLA fromRabbitKidney ................ 89
2
3.3 ReleaseofDHAfromPtdSer.......................... 91
3.4 Receptor-MediatedDegradationofPlasmalogens ......... 91
3.5 Releaseofn–6FattyAcidsfromNeuralMembrane
Glycerophospholipids................................ 92
3.5.1 cPLA inBrain ............................... 92
2
3.5.2 OtherPhospholipasesA ........................ 96
2
3.6 RegulationofPLA ActivityinBrain ................... 96
2
3.6.1 RegulationofPlsEtn-PLA ...................... 96
2
3.6.2 RegulationofcPLA ........................... 97
2
3.7 Conclusion ........................................ 98
References.............................................. 99
4 OxidationofArachidonicandDocosahexaenoicAcidsand
NeurochemicalEffectsofTheirMetabolitesonBrain ............ 105
4.1 Introduction....................................... 105
4.2 ArachidonicAcidandItsEnzymicOxidationinBrain...... 108