Pollock oil supplementation modulates hyperlipidemia and ameliorates hepatic steatosis in mice fed a high-fat diet

Yang Zhi-Hong, Miyahara Hiroko, Takeo Jiro, Hatanaka Akimasa, Katayama, Katayama Masashi

Description

Hyperlipidemia associated with obesity is closely related to the development of atherosclerosis. Both n-3 polyunsaturated fatty acids (PUFAs) and long-chain monounsaturated fatty acids (MUFAs; i.e., C20:1 and C22:1 isomers) supplementation modulate risk factors for metabolic syndrome via multiple mechanisms, including the restoration of impaired lipid metabolism. We therefore examined the effects of pollock oil, which contains a considerable amount of n-3 PUFAs as well as long-chain MUFAs, on plasma hyperlipidemia and hepatic steatosis in diet-induced obese mice. Methods Male C57BL/6J mice (24-26 g) were divided into two groups (n = 10/group) and were fed a high-fat diet containing 32% lard (control group) or 17% lard plus 15% pollock oil (experimental group) for 6 weeks. For both groups, fat comprised 60% of the total caloric intake. Results Although body and liver masses for the two groups did not differ significantly, hepatic lipids concentrations (triglycerides and total cholesterols) were lower ( P < 0.05) after pollock oil ingestion. After 2 weeks on the specified diets, plasma lipid levels (total cholesterol, LDL cholesterol, and triglycerides) significantly decreased ( P < 0.05) in the experimental group compared with the control group, although plasma HDL cholesterol levels did not differ. At the end of 6 weeks, plasma adiponectin levels increased ( P < 0.05), whereas plasma resistin and leptin levels decreased ( P < 0.05) in the experimental mice. Increased levels of long-chain MUFAs and n-3 PUFAs in plasma, liver and adipose tissue by ingesting pollock oil were possibly correlated to these favorable changes. Expression of hepatic genes involved in cholesterol metabolism ( SREBP2 , HMGCR , and ApoB ) and lipogenesis ( SREPB1c , SCD-1 , FAS , and Acac α) was suppressed in the experimental group, and may have favorably affected hyperlipidemia and hepatic steatosis induced by the high-fat diet. Conclusions We demonstrated that pollock oil supplementation effectively improved hyperlipidemia, attenuated hepatic steatosis, and downregulated the express of hepatic genes involved in cholesterol and lipid metabolism in mice with diet-induced obesity.

Sujets

• Monounsaturated fat
• Hyperlipidemia
• Fatty liver
• Adipokine

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 5
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

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RESEARCH

OpenAccess

Pollockoilsupplementationmodulates
hyperlipidemiaandameliorateshepaticsteatosis
inmicefedahigh-fatdiet
Zhi-HongYang
*
,HirokoMiyahara,JiroTakeo,AkimasaHatanakaandMasashiKatayama

Abstract
Background:
Hyperlipidemiaassociatedwithobesityiscloselyrelatedtothedevelopmentofatherosclerosis.Both
n-3polyunsaturatedfattyacids(PUFAs)andlong-chainmonounsaturatedfattyacids(MUFAs;i.e.,C20:1andC22:1
isomers)supplementationmodulateriskfactorsformetabolicsyndromeviamultiplemechanisms,includingthe
restorationofimpairedlipidmetabolism.Wethereforeexaminedtheeffectsofpollockoil,whichcontainsa
considerableamountofn-3PUFAsaswellaslong-chainMUFAs,onplasmahyperlipidemiaandhepaticsteatosisin
diet-inducedobesemice.
Methods:
MaleC57BL/6Jmice(24-26g)weredividedintotwogroups(n=10/group)andwerefedahigh-fat
dietcontaining32%lard(controlgroup)or17%lardplus15%pollockoil(experimentalgroup)for6weeks.For
bothgroups,fatcomprised60%ofthetotalcaloricintake.
Results:
Althoughbodyandlivermassesforthetwogroupsdidnotdiffersignificantly,hepaticlipids
concentrations(triglyceridesandtotalcholesterols)werelower(
P
<0.05)afterpollockoilingestion.After2weeks
onthespecifieddiets,plasmalipidlevels(totalcholesterol,LDLcholesterol,andtriglycerides)significantly
decreased(
P
<0.05)intheexperimentalgroupcomparedwiththecontrolgroup,althoughplasmaHDL
cholesterollevelsdidnotdiffer.Attheendof6weeks,plasmaadiponectinlevelsincreased(
P
<0.05),whereas
plasmaresistinandleptinlevelsdecreased(
P
<0.05)intheexperimentalmice.Increasedlevelsoflong-chain
MUFAsandn-3PUFAsinplasma,liverandadiposetissuebyingestingpollockoilwerepossiblycorrelatedtothese
favorablechanges.Expressionofhepaticgenesinvolvedincholesterolmetabolism(
SREBP2
,
HMGCR
,and
ApoB
)and
lipogenesis(
SREPB1c
,
SCD-1
,
FAS
,and
Acac
a
)wassuppressedintheexperimentalgroup,andmayhavefavorably
affectedhyperlipidemiaandhepaticsteatosisinducedbythehigh-fatdiet.
Conclusions:
Wedemonstratedthatpollockoilsupplementationeffectivelyimprovedhyperlipidemia,attenuated
hepaticsteatosis,anddownregulatedtheexpressofhepaticgenesinvolvedincholesterolandlipidmetabolismin
micewithdiet-inducedobesity.
Keywords:
Pollockoil,n-3PUFA,MUFA,hyperlipidemia,hepaticsteatosis,adipokines

Background
consequenceofhyperlipidemiaareoxidizedandattract
Hyperlipidemia,amedicalconditioncharacterizedbyinflammatorymonocytes,whichdifferentiateinto
increasedbloodlevelsoflipidsincludingcholesterolandmacrophagesthattakeuptheoxidizedlipid.Oxidation
triglycerides,isacriticalcomponentofmetabolismsyn-oflow-densitylipoproteins(LDLs)inthearterialwallis
dromeaswellasapossiblepredisposingfactorforamajorandphysiologicallyrelevantmechanismforthe
atherosclerosis,aleadingcauseofdeathworldwide[1,2].pathogenesisofatherosclerosis,andthepresenceof
Lipidsthataccumulateinthearterialwallasalipid-loadedmacrophagefoamcellsinthearteryintima
isapredictorforthedevelopmentofatherosclerotic
*Correspondence:[e-mail]
lesions.Acloserelationshipexistsbetweendietaryfats
CentralResearchLaboratory,TokyoInnovationCenter,NipponSuisanKaisha,
anddyslipidemia-relatedevents[3].Althoughan
Ltd.,32-3Nanakuni1ChomeHachioji,Tokyo192-0991,Japan
©2011Yangetal;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommons
AttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,andreproductionin
anymedium,providedtheoriginalworkisproperlycited.

Yang
etal
.
LipidsinHealthandDisease
2011,
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:189Page2of10
http://www.lipidworld.com/content/10/1/189
increasedintakeofsaturatedfattyacidsispathogenicfor
Table1Fattyacidcompositionofdietaryfats(%)
coronaryheartdisease,numerousstudieshavedemon-
FattyacidLardPollockoil
stratedaprotectiveeffectofn-3polyunsaturatedfatty
C14:01.54.9
acids(PUFAs)throughavarietyofmechanisms,includ-
C16:025.49.8
ingreductionoftriglyceridesandvery-low-densitylipo-
C16:12.46.1
proteins[4].Inaddition,wehaveshownthatmarine-
C18:05.91.7
derivedlong-chainmonounsaturatedfattyacids
C18:140.614.3
(MUFAs)(i.e.,C20:1andC22:1isomers)modulate
C18:2n-610.81.3
metabolicsyndromebyrestoringimpairedglucoseand
C18:3n-31.01.1
lipidmetabolism[5].Therefore,fishoilsthatarerichin
C20:1n-90.89.1
bothn-3PUFAsandlong-chainMUFAsmayhelpalle-
C20:1n-7ND3.3
viatehypercholesterolemiaandhypertriacylglyceridemia.
C22:1n-11ND12.3
Alaskapollock(
Theragrachalcogramma
)isaNorth
C22:1n-9ND1.6
Pacificspeciesofthecodfamily,Gadidae.Pollockoil
C20:5n-30.0210.3
containsconsiderableamountsofn-3PUFAsandlong-
C22:5n-30.11.2
chainMUFAs[6].TheAlaskapollockfishingindustryis
C22:6n-30.037.9
thelargestintheUnitedStatesandoneofthelargestin
Valuescorrespondtomeanofthreeseparatesamplesprocessed
theworld.Inrecentyears,pollockfishinghasaccounted
independently.
for~30%ofallU.S.seafoodlandingsbymass[7].
ND:Notdetected.
Althoughpollockoilisusedinboththefoodandfeed
industries[8],littleisknownabouttherelationshipstudy.MaleC57BL/6Jmice(5weeksold)wereobtained
betweendietarypollockoilandhyperlipidemia.GivenfromCharlesRiverLaboratoriesJapanInc.(Yokohama,
thehealthbenefitsofn-3PUFAsandlong-chainMUFAs,Japan)andhousedatNihonBioresearchat23±1°C
weexaminedtheeffectofdietarypollockoilonhyperli-undera12/12hlight-darkcycle.Theanimalswerepro-
pidemiainmicewithdiet-induceddyslipidemia.videdfreeaccesstowaterandstandardmousechow
CRF-1(OrientalYeastCo.Ltd.,Tokyo,Japan)fora1-
Methods
weekacclimatizationperiod.
Measurementoffattyacidcompositionofdietaryoils
Afteracclimatization,micewererandomlyassignedto
CamerialardwaspurchasedfromRomiSmilfoodB.V.oneoftwogroupsforthe6-weekfeedingexperiment.The
(Heerenveen,Netherlands).Pollockoilwasobtainedcontrolgroup(n=10)wasfedahigh-fatdietcontaining
fromNipponSuisanKaisha,Ltd.(Tokyo,Japan)and32%lard(D12492RodentDietwith60kcal%Fat;Research
refinedwithsilicagelandactivatedclaysandthenDiets,Inc.,NJ,USA)andtheexperimentalgroupwasfeda
steam-distillationdeodorized.Allstandardandextracteddietsupplementedwithpollockoil(17%lardplus15%pol-
lipidswerestoredat-20°Cuntilused.Fattyacidcompo-lockoil).Tocontrolfortotalfatintake,thetotalfatcontent
sitionsofthedietaryfats(Table1)weredeterminedinbothdietscorrespondedto60%ofthecaloricintake.
aftermethylationofsampleswith14%(w/v)borontri-ThecompositionsofthedietsarelistedinTable2.Body
fluoride/methanol(SigmaChemicalCo.,St.Louis,massandfoodintakeweremonitoredthroughoutthe
USA.)at80°Cfor30min.Theresultingfattyacidstudy.Attheendoftheinterventionperiod,micewere
methylesterswerequantifiedbygaschromatography
usinganAgilent6890NNetworkGasChromatograph
System(AgilentTechnologiesJapan,Ltd.,Tokyo,Japan)
Table2Dietcompositions
equippedwithasplitinjector,FIDdetector,andfused
IngredientLarddiet(g/100gdiet)POdiet(g/100gdiet)
silicacapillarycolumn(DB-WAX,30m×0.25mmI.D.
Casein25.825.8
×0.25
μ
mfilmthickness,J&WScientific,Agilent
l-Cysteine0.40.4
Technologies).Methylesterswereidentifiedbycompari-
Maltodextrin1016.216.2
sonofretentiontimestothoseoffattyacidmethylester
Sucrose8.98.9
standards(Nu-ChekPrep,Inc.,Elysian,MN,USA).Pol-
Cellulose6.56.5
lockoilcontainsconsiderablelevelsoflong-chain
Mineralmixture1.31.3
MUFAsandn-3PUFAs(C20:1aswellasC22:1isomers
Vitaminmixture1.31.3
andn-3PUFAscombined:~45%).
Cholinebitartrate0.30.3
Soybeanoil3.23.2
Animalsanddiets
Lard3217
TheInstitutionalAnimalCareandUseCommitteeat
Pollockoil
–
15
NihonBioresearchInc.(Gifu,Japan)approvedthis
POdiet:Pollockoil-supplementeddiet.

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anesthetizedwith4%sodiumpentobarbital(Dainippon
SumitomoPharma,Osaka,Japan),andbloodwascollected
byabdominalveinpuncture.Plasmawasobtainedbycen-
trifugationat1000gfor15minandstoredat-80°Cuntil
analyses.Vitalorganswereremovedandweighedaftera
shortwashincoldphosphate-bufferedsaline,pH7.4.
Mesentericwhiteadiposetissue(WAT)andLiverswere
keptat-80°Cforthefurtherlipidextractionandquantita-
tivepolymerasechainreaction(QPCR)analysis.
Lipidextractionandfattyacidanalysis
Thefattyacidcompositionsofplasma,liverandWAT
intheC57BL/6Jmiceweredeterminedasdescribed
before[5].Lipidswereextractedbyhomogenizingthe
tissuesamplesinamethanol/hexanesolution(4:1v/v)
addedwithbutylatedhydroxytoluene(BHT,50
μ
g/mL)
asanantioxidant.Thesamplesweremethylatedwith
acetylchloride,andthefattyacidmethylesterswere
separatedandquantifiedb