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-Tocopherol Is Responsible for the Delayed Postnatal Development in Offspring of Rats Fed Fish Oil Instead of Olive Oil during Pregnancy and Lactation1
Facultad de Ciencias Experimentales y Técnicas, Universidad San Pablo-CEU, E-28668 Boadilla del Monte (Madrid), Spain
2To whom correspondence should be addressed.
 |
ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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-Tocopherol concentration was lower in maternal and fetal plasma,
liver and brain in the FOD group than in the OOD group. The postnatal
increase in body weight and length was less and body and
psychomotor maturation indices were delayed in pups from
FOD-fed dams compared with those from OOD-fed dams. This
difference was maintained when pups were cross-fostered at birth,
with the delay in postnatal development present in the pups suckling
dams fed FOD during lactation. At age 21 d, pups suckling dams fed
FOD had lower AA and higher EPA and DHA concentrations in brain
phospholipids. Although -tocopherol in plasma and liver was lower in
pups suckling dams fed FOD rather than OOD, brain -tocopherol
concentrations did not differ. Milk yield and milk -tocopherol and
AA concentrations were lower and EPA and DHA were higher in the milk of
dams fed FOD compared with those fed OOD. Postnatal development indices
and the proportion of plasma, liver and brain AA concentrations,
although not plasma, liver and brain -tocopherol concentrations,
recovered to the values found in dams fed OOD when the FOD was
supplemented with 
-linolenic acid. However, postnatal development
indices were not recovered when the FOD was supplemented with
sufficient exogenous vitamin E to increase plasma and liver
-tocopherol concentrations above those in dams fed OOD. Thus,
although feeding FOD during pregnancy and lactation decreases both
-tocopherol and AA concentrations, the latter deficiency rather than
the former seems to be responsible for delayed postnatal development of
rat pups.
KEY WORDS: • fish oil diet • olive oil diet • arachidonic acid • -tocopherol • rats
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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,
Clandinin et al. 1980
, Jumpsen and Clandinin 1995
). DHA is of major importance for the developing infant
because is a major part of the total fatty acids in cerebral cortex and
retina phospholipids (Clandinin et al. 1980
,
Fleisler and Anderson 1983
), and AA is the precursor of
prostaglandins and leukotrienes (Zurier 1993
) and is
essential for neonatal growth (Carlson et al. 1992
).
During pregnancy, these fatty acids are transported from maternal
circulation across the placenta (Ruyle et al. 1990
), and
the fatty acid composition of developing neural tissues can be altered
in animals through changes in prenatal and/or postnatal dietary fatty
acid composition (Arbuckle and Innis 1992
,
Carlson et al. 1986
, Yonekubo et al. 1993
). These alterations affect neurodevelopment as shown by
changes in several neurochemical and behavioral variables (Saste et al. 1998
) and learning ability (Suzuki et al. 1998
, Yonekubo et al. 1994
). Excess intake of
(n-3) fatty acids, such as that caused by high dietary concentrations
of fish oil, decreased the endogenous concentrations of AA
(Bourre et al. 1988
and 1990
) due to an inhibitory
effect on 
6 desaturase activity (Raz et al. 1997
).
Dietary supplementation with fish oil is still controversial. High
dietary fish oil consumption during pregnancy in rats has been shown to
improve postnatal learning ability (Yonekubo et al. 1994
), and women have been advised to increase the consumption
of sardines and fish oil during pregnancy to promote higher
concentrations of DHA in the newborn infant (Connor et al. 1996
). In addition, fetal DHA reserves have been improved by
supplementing pregnant women with fish oil during the last trimester of
pregnancy (Van Houwelingen et al. 1995
). However,
several studies have shown that postnatal supplementation with marine
oil led to impaired growth, resulting in lower weight, length and head
circumference (for a review on the subject, see Hamosh 1998
), an effect that was related to the lower AA
concentrations (Carlson and Werkman 1993
).
Excess intake of PUFA enhances lipid peroxidation (Berry et al. 1991
) and reduces antioxidant capacity (Cho and Choi 1994
), enhancing susceptibility to oxidative damage
(Mazière et al. 1998
), a condition that during
pregnancy may be responsible for fetal damage (Simán and Eriksson 1997
, Viana et al. 1996
). Therefore,
the potential negative effect on offspring of high dietary fish oil
intake during pregnancy could be affected not only by decreased AA
concentrations but also by decreased vitamin E concentrations. On the
contrary, dietary olive oil protects the (n-3) PUFA series
(Navarro et al. 1994
), which have been shown not to
affect AA concentrations (Girón et al. 1989
,
Periago et al. 1990
, Rao et al. 1993
) and
consequently have been proposed to be taken into account in nutritional
recommendations (Bourre et al. 1997
). In addition,
monounsaturated fatty acids are much more resistant to lipid
peroxidation (Berry et al. 1991
, Öztezcan et al. 1996
, Scaccini et al. 1992
), and
therefore their abundance in the diet could be protective against the
loss of vitamin E, which is the main lipophilic antioxidant vitamin.
Therefore, the present study in rats was designed to compare the
effects of a diet supplemented during pregnancy and lactation with fish
oil versus olive oil on the fatty acid profile and vitamin E
concentration of the offspring. Because a decreased postnatal growth
rate, as well as a decrease in both AA and vitamin E concentrations,
was found in the offspring of rats fed the fish oil–rich diet, the
study was extended to determine whether dietary supplementation with
either vitamin E, AA or -linolenic acid [18:3(n-6)], as a
precursor of AA, could ameliorate these changes, as well as to
determine whether the cross-fostering between the offspring and
dams during lactation would affect the response.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Female Sprague-Dawley rats from our animal quarters were
initially fed a standard nonpurified diet (B&K Universal, Barcelona,
Spain) and housed under controlled light and temperature conditions
(12-h light/dark cycle; 22 ± 1°C). The experimental protocol
was approved by the Animal Research Committee of the University San
Pablo-CEU in Madrid, Spain. Rats were mated when they weighed
180–190 g, and on the day in which spermatozoids were found in vaginal
smears (d 0 of pregnancy), they were divided into two groups that were
fed purified diets that differed only in the nature of the nonvitamin
lipid component: one contained 10 g fish oil/100 g diet acids
(FOD) and the other contained 10 g olive oil/100 g diet (OOD). The
composition of these diets and their proportional fatty acid contents
are shown in Tables 1
and
2
. Both diets contained a similar amount of vitamin E (Table 2)
; they
both were isoenergetic (both providing 
16.24 kJ/g) and were fed to
the rats on an ad libitum basis. Diets were prepared at the onset of
the experiments and were divided into daily portions that were kept at
-20°C until use. Dams were housed in collective cages (four per
cage) and had free access to the assigned diet and tap water. Fresh
food was provided every 24 h, and the daily food intake was
estimated periodically.
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Experiment 2.
Another set of pregnant rats fed either FOD or OOD as described were
allowed to spontaneously deliver. Litters were adjusted to eight pups
that suckled their dams. Pups and dams were fed freely the
corresponding diet throughout the lactation period. The body weight and
length (crown-to-rump length) were measured at different days of age.
Opening of the eyelids, opening of the ear and the acquisition of both
the surface righting reflex (SRR) and the air righting reflex (ARR)
were tested as described previously (Lopez Tejero et al. 1986
) on the appropriate days until the age of 20 d.
Results are expressed as the cumulative percentage of pups per litter
attaining mature responses. Dams and pups were decapitated as described
at d 21 after delivery. The brains and livers of each pup were rapidly
removed, placed into liquid nitrogen and kept at -80°C until
processed.
Experiment 3.
Another set of rats were fed the same diets as described earlier during
pregnancy and lactation, and milk yield was estimated from pup weight
and weight gain on d 7–8 and 14–15 of lactation as described
previously (Sampson and Jansen 1984
). On d 10, after
being separated from their litters, dams were anesthetized with 0.5
mL/200 g of a cocktail containing 9 mg ketamine (Imalgene 500; Rhone
Merieux, Lyon, France) and 0.25 mg chlorpromazine (Largactil; Rhone
Poulenc, Madrid, Spain) administered intraperitoneally. The rats were
injected intraperitoneally with 0.25 mL/200 g of a solution of oxytocin
(2000 IU/L Syntocinón; Novartis Farmaceutica,
Barcelona, Spain), and milk was obtained with gentle hand stripping of
the teats. An aliquot of milk was immediately placed into
chloroform/methanol (2:1) for lipid extraction (Folch et al. 1957
), and another aliquot was kept at -80°C until
processed.
Experiment 4. Another set of rats were fed FOD or OOD during pregnancy and lactation, but at the time of delivery, litters were cross-fostered. Thus, pups of dams fed FOD suckled dams fed OOD (FOD-OOD), and pups of dams fed OOD suckled dams fed FOD (OOD-FOD). Other litters were allowed to suckle from different dams that had been fed the same diet as were fed their actual dams during pregnancy (FOD-FOD and OOD-OOD), and all pups were studied in parallel. Litter size was always kept to eight per dam. Body weight, length and the different maturation tests were studied as described, and the dams and pups from all of the groups were decapitated on d 21 of lactation according to the same protocol described earlier.
Experiment 5.
Other rats were fed modified FOD during pregnancy and lactation. FOD
was supplemented with 1 g of dl--tocopherol
acetate/kg (FOD-VE), or the fish oil content was reduced to 8% and the
diet was supplemented with 2% borage oil (Larodan Fine
Chemicals, Malmö, Sweden) with a -linolenic acid [18:3(n-6)]
content of >40% (FOD-L) or with ARASCO (Martek Biosciences,
Columbia, MD), which is a triglyceride oil that contains >40% AA, no
(n-3) fatty acids and small amounts of other long-chain PUFA
(FOD-AA) (Tables 1
, 2)
. The vitamin E contents in these diets were
similar except for FOD-VE, in which the vitamin E was >10 times
higher than that of any of the other diets. In this experiment, pups
were allowed to suckle their dams, and body and psychomotor maturation
were studied as described earlier, with the pups killed on d 21 after
delivery.
Processing of samples
Lipid extraction and purification (Folch et al. 1957
) were carried out with fresh aliquots of each diet, as
well as with plasma (separated from fresh blood through centrifugation
at 1500 x g for 15 min at 4°C), milk, frozen livers,
adipose tissues and brains. Phospholipids were separated through thin
layer chromatography in Silicagel 60
F254, as described elsewhere (Ruiz and Ochoa 1997
). Spots corresponding to phospholipids were eluted
with methanol/toluene (4:1). Total lipid or phospholipid fatty acids
were simultaneously saponified and methylated according to the method
of Lepage and Roy (1984
and 1986)
. Fatty acid
methyl esters were separated and quantified on a Perkin–Elmer gas
chromatograph (Autosystem; Norwalk, CT) with a flame ionization
detector and a 30-m x 0.25-mm Omegawax capillary column. Nitrogen
was used as carrier gas, and the fatty acid methyl esters were compared
with purified standards (Sigma Chemical Co., St. Louis, MO). Individual
fatty acids are expressed as percent of total fatty acids in the
sample.
-Tocopherol was measured in plasma, milk, liver and brain samples
through HPLC, according to methods previously described (Barbas et al. 1997
, Barbas and Herrera 1998
).
-Tocopherol and -tocopheryl acetate were measured in fresh diets
(Rupérez et al. 1999
) and expressed as
-tocopherol.
Statistical analysis
Data are expressed as means ± SEM. Treatment
effects (diet) were analyzed by one-way ANOVA with Systat Version
5.03a (Wilkinson, Evanston, IL). When treatment effects were
significantly different (P < 0.05), means were tested
by Tukey’s test, and linear regressions were calculated by the
least-squares method (Quaresima et al. 1996
).
Differences between two groups were analyzed by Student’s t
test. Significance was set at the = 0.05 error rate.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The fatty acid composition of plasma of rats fed FOD contained
significantly less oleic acid [18:1(n-9)] and AA [20:4(n-6)] and
more DHA [22:6(n-3)] and eicosapentaenoic acid [EPA, 20:5(n-3)]
than the plasma of rats fed OOD (Table 3
). A similar difference in the proportion of fatty acids was seen in
both maternal liver and lumbar adipose tissue, except that in adipose
tissue, the amount of AA was practically undetectable in both groups
and the proportion of both myristic [14:0] and palmitoleic
[16:1(n-7)] acids was higher in rats fed FOD than in rats fed OOD
(Table 3)
. In fetal plasma, the proportions of the different fatty
acids did not differ between the groups, except for palmitic acid
[16:0], AA and linoleic acid. Palmitic acid was higher and both AA
and linoleic acid [18:2(n-6)] were lower in fetuses of dams fed FOD
rather than OOD; the difference was especially striking for AA, being
barely detectable in plasma of fetuses of dams fed FOD (Table 3)
. In
fetal liver, the proportions of stearic acid [18:0], EPA and DHA were
higher, whereas the proportions of oleic acid and AA were lower in the
former (Table 3)
. Similarities in the fatty acid profile between
maternal plasma and fetal liver prompted us to calculate linear
correlations with individual values, and we found that although the
correlation was not significant when all saturated fatty acids were
considered (r = 0.04, n = 10), it was
significant when either monounsaturated fatty acids (r
= 0.73, n = 10, P < 0.05) or
(n-6)- (r = 0.89, n = 9, P
< 0.01) or (n-3)- (r = 0.86, n = 10, P < 0.01) PUFA were considered.
|
-tocopherol in both maternal and fetal plasma
as well as in fetal liver and brain were significantly lower in the FOD
group than in the OOD group (Table 4
).
|
). The length of the pups did not differ between groups up
to age 10 d, but from then on, pups of dams fed FOD were shorter
than those of dams fed OOD (Fig. 1B
). Several tests related
to body and psychomotor maturation were carried out in these pups, and
results showed that either eye or auditive duct opening, as well as ARR
or SRR acquisition, occurred earlier in the pups of dams fed OOD than
in the pups of dams fed FOD (Fig. 2
). These pups were killed at d 21 of suckling, and their plasma had
higher palmitoleic acid concentrations, whereas both EPA and DHA were
much higher in those suckling dams fed FOD rather than OOD. Oleic and
linoleic acids and AA were lower in those suckling dams fed FOD rather
than OOD (Table 5
). Livers of pups suckling dams fed FOD had higher stearic acid, EPA and
DHA and lower oleic and linoleic acid and AA than those suckling dams
fed OOD (Table 5)
. In brain phospholipids, the proportion of AA was
lower and the proportions of myristic acid, EPA and DHA were higher in
pups suckling dams fed FOD compared with those suckling dams fed OOD
(Table 5)
. The concentration of -tocopherol was significantly lower
in plasma and liver of pups suckling dams fed FOD than of pups of dams
fed OOD, whereas -tocopherol in brain did not differ between the two
groups (Table 5)
.
|
|
|
). Similar intergroup relationships were found in the body and
psychomotor maturation indices studied, because both the eye and
auditive duct opening and both the ARR and the SRR acquisition occurred
later in the FOD-FOD and OOD-FOD pups than in either
FOD-OOD or OOD-OOD pups, although for both ARR and SRR, the
difference between OOD-FOD and FOD-OOD was not significant
(P = 0.506 and 0.257) (Fig. 4
).
|
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). In plasma, EPA and DHA were lower and oleic acid and AA were higher
in both FOD-OOD and OOD-OOD than in FOD-FOD or OOD-FOD
pups. In liver, myristic and oleic acids and AA were higher, whereas
both EPA and DHA were lower in FOD-OOD and OOD-OOD than in
FOD-FOD or OOD-FOD. In brain phospholipids, EPA and DHA were
lower and linoleic acid and AA were higher in FOD-OOD and
OOD-OOD than in either FOD-FOD or OOD-FOD (Table 6)
.
-Tocopherol concentrations in both plasma and liver were much higher
in pups from the FOD-OOD and OOD-OOD groups than in pups from
the FOD-FOD and OOD-FOD groups, whereas in brain, no
differences were found among the four groups (Table 6)
.
|
), although food intake did not differ between the two groups (data not
shown). Although the concentration of total fatty acids in milk (mainly
in the form of triglycerides) did not differ between the two groups
(data not shown), the proportions of myristic acid, palmitic acid,
stearic acid, palmitoleic acid, DHA and EPA were higher and
the proportions of oleic acid and AA were lower in milk from rats fed
FOD than in milk from those fed OOD (Table 7)
. The concentration of
-tocopherol in milk from FOD-fed rats was much lower than that
from OOD-fed rats (Table 7)
.
|
-tocopherol in pups of lactating dams fed FOD may have contributed
to their decreased growth and body and psychomotor maturation. To
determine which of these two components was responsible for the
effects, during lactation the FOD was supplemented with either
-linolenic acid [18:3(n-6)] as substrate for endogenous AA
synthesis (FOD-L), AA (FOD-AA) or vitamin E (FOD-VE) (expt. 5).
Substantial amounts of -linolenic acid were present in FOD-L and
of AA in FOD-AA, both of which were practically absent in the other
diets (Table 2)
. A similar concentration of vitamin E was present in
all diets, except for the FOD-VE, in which the vitamin E
concentration was >10 times higher than that in any other diet (Table 2)
. Compared with pups suckling dams fed OOD, both body weight and
length were significantly lower in FOD or FOD-VE pups, whereas no
difference was found between those of OOD and FOD-L pups, and the
pups of dams fed FOD-AA had a lower body weight than those of dams
fed OOD, although length did not differ (Table 8
). The date of acquisition of either ARR or SRR was also delayed in pups
of dams fed FOD, FOD-AA or FOD-VE compared with those from dams
fed OOD, whereas no differences were found between pups of dams fed OOD
or FOD-L diets (Table 8)
.
|
). Compared with pups of dams fed OOD, -tocopherol concentration in
plasma and liver was greater in pups of dams fed FOD-VE than in any
of the other groups, whereas values in pups of dams fed OOD were higher
than those of pups of dams fed FOD, FOD-L or FOD-AA (Table 9)
.
However, brain -tocopherol did not differ among the groups (Table 9)
.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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-tocopherol
occurs in both in dams and fetuses when rats are fed a diet with a
moderate amount of fish oil (10%) as the only nonvitamin fat component
in comparison with those fed the same diet but containing olive oil
instead of fish oil during pregnancy, and a similar effect is found
21 d after delivery in pups when the dietary treatment is
maintained during lactation. In fact, when pups from rats fed FOD were
studied during suckling, a decreased growth rate and a delay in the
acquisition of body and psychomotor maturation indices were found with
the AA and -tocopherol deficiencies. The effect was also found when
newborns of rats fed OOD during pregnancy were cross-fostered to
rats fed FOD.
The fatty acid profile in adipose tissue in rats fed either diet during
pregnancy was very similar to the composition of the diet, including a
lack of AA in rats from either group and an enhanced proportion of DHA
and EPA at the expense of oleic acid in adipose tissue of rats fed FOD.
Most of the fat accumulated in adipose tissue comes from the diet due
to its low capacity to synthesize fatty acids (Shargo et al. 1969
), and although lipogenesis is enhanced in this tissue
during pregnancy (Palacín et al. 1991
), maternal
hyperphagia and unchanged or even enhanced adipose tissue lipoprotein
lipase activity during early gestation (Knopp et al. 1975
) allow dietary fatty acids circulating in plasma in the
form of triglyceride-rich lipoproteins (chylomicrons and VLDL) to
be taken up by the tissue. Different from adipose tissue, a substantial
amount of AA appeared in both liver and plasma of rats fed OOD,
probably as result of its active synthesis from linoleic acid
[18:2(n-6)] in liver. This was, however, not the case in rats fed
FOD, in which the enhanced content of both DHA and EPA could have
caused the competitive inhibition of 6-desaturase
(Christiansen et al. 1991
, Raz et al. 1997
and 1998
), the rate-limiting reaction for the conversion of
linoleic acid to -linolenic acid in the synthesis of AA. Our finding
that supplementation with -linolenic acid in lactating rats fed FOD
overcame the deficiency of AA in their suckling newborns further
supports this hypothesis.
Except for saturated fatty acids, which show a higher proportion in
fetal compared with maternal structures, probably as result of the
well-recognized lipogenic capability of fetal liver (Lorenzo et al. 1981
), similar changes in the fatty acid profile were
detected in both fetal plasma and liver, as well as in maternal sites.
Preferential uptake of both monounsaturated and PUFA by the placenta
and their consequent transfer to the fetus seem to be mediated via the
placental plasma membrane fatty acid–binding protein
(p-FABPpm), as recently reviewed
(Dutta-Roy 2000
), and although the process has
different preferences depending on the type of fatty acid, the
present findings show that the correlation is significant for
monounsaturated and for either (n-6) or (n-3) PUFA. Although precursor
PUFA may be elongated and desaturated in the rat fetus and no exogenous
supply of 20:4(n-6) or 22:6(n-3) should be required if the precursor
lipids, 18:2(n-6) and 18:3(n-3), respectively, are adequate in the diet
(Hachey 1994
), the present findings show that an excess
of (n-3) fatty acids in maternal diet causes a specific deficiency of
AA in the fetus, with the effect being a consequence of either the
inhibitory action of (n-3) fatty acids on 6 desaturation within the
fetus or an altered proportional fatty acid placental transfer
secondary to the changes taking place in the maternal side or both.
The present findings also show that a proportional excess of dietary
PUFA enhances the depletion of -tocopherol, causing a deficient
condition of this antioxidant in both the dam and the fetus. The
feeding of fish oil enhances vitamin E requirements (Cho and Choi 1994
), probably as a consequence of the effect of PUFA
enrichment on enhancement of lipid peroxidation (Mazière et al. 1998
). This condition contrasts with the decreased
susceptibility to lipid peroxidation that occurs when rats are fed
diets supplemented with olive oil (Öztezcan et al. 1996
), allowing appropriate endogenous concentrations of
-tocopherol, as seen in the present study in both pregnant rats and
fetuses. Despite the decreased AA and -tocopherol concentrations in
fetuses of pregnant rats fed FOD, litter size and fetal weight were
unaffected, and a similar finding was reported by others who subjected
rats during pregnancy to different dietary fat compositions
(Buison et al. 1997
) or even under conditions of
decreased -tocopherol concentration (Schinella et al. 1999
). These findings support the notion that during pregnancy
in rats, neither substantial changes in dietary fatty acids nor an
antioxidant-deficient condition affects pregnancy outcome, probably
because in this species a substantial part of the development of neural
tissue occurs postnatally (Dobbing and Sands 1979
), as
is also the case in humans (Pomeroy and Segal 1998
).
This view is supported in the present study by the findings in the
cross-fostering experiments, in which pups born to dams fed FOD
during pregnancy showed a postnatal growth rate and psychomotor
maturation indices similar to those of pups of dams fed OOD when
allowed to suckle from dams fed OOD.
An important delay in growth rate and psychomotor development was seen
in pups suckling dams fed FOD during lactation. The effect could be the
result of either the decreased milk yield or the altered fatty acid
composition in milk detected in these rats, with the latter reflecting
their plasma fatty acids profile, or both. A decreased availability of
milk during suckling, such as that caused by maternal underfeeding in
pair-fed nutritional controls of lactating rats fed alcohol,
decreases pup growth rate (Tavares do Carmo et al. 1999
), but sensory maturation indices seem to be less affected
(Lopez Tejero et al. 1986
). The feeding of FOD during
lactation also caused a depletion of -tocopherol in plasma and liver
and a major alteration in neural fatty acid composition, with a
specific decline in AA in brain phospholipids. Both of these changes,
the -tocopherol deficiency and the decline in AA in brain
phospholipids, could have affected neurodevelopment in the pups,
because similar results were reported for pups of dams fed a fish
oil–supplemented diet throughout pregnancy and lactation (Saste et al. 1998
). In adult rats fed a fish oil–supplemented diet,
monoaminergic neurotransmission and behavior were affected
(Chalon et al. 1998
), and in adults subjected to a
vitamin E deficiency regimen, a disturbance of monoamine metabolism in
brain was observed (Adachi et al. 1999
). In an attempt
to determine which of these two effects (decreased AA in brain
phospholipids or -tocopherol deficiency) was responsible for the
delayed growth rate and neurodevelopment in pups of dams fed FOD, a
dietary supplement experiment was carried out. In this experiment,
conditions that restored brain AA content rather than plasma and liver
concentrations of -tocopherol avoided the negative effects of the
feeding of FOD during lactation. The effect was more evident when
-linolenic acid rather than AA was supplemented to FOD, although
both treatments restored brain phospholipid AA content to the same
concentration as in pups whose dams were fed OOD. The only difference
was the absence of linoleic acid [18:2(n-6)] in brain phospholipids
when rats were supplemented with AA, whereas it was present in those
supplemented with -linolenic acid at a concentration that did not
differ from that of those whose dams were fed OOD. Regarding the
different response to supplementation with -linolenic acid versus
with AA, although it was previously found in humans that diets rich in
AA decrease the proportion of linoleic acid in plasma phospholipids
(Sinclair and Mann 1996
), the effect is likely a
consequence of the replacement by AA of linoleic acid in tissues
(Whelan 1996
). It is, however, worth emphasizing the
exquisite capability of the brain to buffer exaggerated increments in
plasma concentrations of AA, as shown in pups of dams fed FOD
supplemented with AA, which had much higher plasma concentrations than
any of the other groups, whereas the proportional content in brain
phospholipids did not differ from those of dams fed either OOD or FOD
supplemented with -linolenic acid.
The supplementation of vitamin E to lactating rats fed FOD enhanced
plasma and liver -tocopherol concentrations in pups but did not
modify the concentration in brain compared with pups of dams fed OOD.
It has previously been shown in humans that even high oral
-tocopherol supplementation did not increase ventricular
cerebrospinal fluid -tocopherol concentrations (Pappert et al. 1996
), and in rats, -tocopherol intake modestly
increases brain -tocopherol (Martin et al. 1999
,
Vatassery et al. 1988
), with the change being much
smaller than that in plasma and other tissues, including the liver. In
fact, the turnover or exchange half-life rate of -tocopherol in
the nervous system is much slower than that in plasma (Vatassery 1992
), and the brain uptake index of -tocopherol in mice is
very low (Adams and Wang 1994
). Furthermore, the high
content of PUFA and, more specifically, DHA in brain phospholipids in
pups suckling dams fed FOD supplemented with vitamin E may have
enhanced the consumption of antioxidants and thus may impeded the
increase in brain -tocopherol concentration over the values for pups
of dams fed OOD. Because vitamin E deficiency plays a role in the
disturbance of monoamine metabolism in rat brain (Adachi et al. 1999
), there is no way to determine whether this
condition aggravates the nervous system function caused by the altered
fatty acid profile of these animals. However, the fact that
supplementation of -linolenic acid to the lactating rats fed FOD
increased the AA content of brain phospholipids in their pups and
normalized body weight and psychomotor maturation variables despite
their low -tocopherol concentrations supports a more important role
of the appropriate availability of AA rather than vitamin E on
postnatal development.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: AA, arachidonic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FOD, fish oil diet; FOD-L, fish oil diet supplemented with -linolenic acid; FOD-VE, fish oil diet supplemented with vitamin E; OOD, olive oil diet; PUFA, polyunsaturated fatty acids.
Manuscript received May 30, 2000. Initial review completed July 3, 2000. Revision accepted August 7, 2000.
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REFERENCES |
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