1: Rev Neurol 1999 Jan;28 Suppl 1:S59-64
[Treatment of generalized peroxisomal disorders with docosahexaenoic
acid ethyl
ether].
[Article in Spanish]
Martinez M, Vazquez E, Garcia-Silva MT, Beltran JM, Castello F, Pineda
M, Mougan
I
Hospital Materno-Infantil Vall d'Hebron, Barcelona, Espana. mmartinez@cinet.es
INTRODUCTION: We found that patients with the Zellweger syndrome and
other
generalized peroxisomal disorders have a dramatic decrease of docosahexaenoic
acid (DHA, 22:6n-3) in the blood, brain, retina and other tissues.
DHA is
believed to play an important role in the brain and retina. DEVELOPMENT:
Patients with the Zellweger syndrome and its variants have severe cerebral
and
retinal defects that could be related to their DHA deficiency. With
this
rationale, we have been treating peroxisomal-disorder patients with
a DHA
derivative of a high degree of purity (DHA ethyl ester, > 90% pure)
since 1991.
So far, we have treated 13 DHA-deficient peroxisomal patients, one
with the
classic Zellweger syndrome and 12 with milder variants of the disease.
This
paper presents the follow-up of these DHA-treated patients. In summary,
we have
found important improvements in liver function, in the plasmalogen
levels and in
the two ratios 26:0/22:0 y 26:1/22:0, diagnostic of the disease. We
have also
found clear clinical improvements in most cases. Most significantly,
magnetic
resonance imaging has shown advances in brain myelination, so far in
6 of the
treated patients. CONCLUSION: We strongly recommend treatment with
DHA ethyl
ester in all DHA-deficient patients with generalized peroxisomal disorders.
Logically, treatment should be started as soon as possible, in the
hope of
preventing cerebral and visual damage.
PMID: 10778491, UI: 20240959
2: Anticancer Res 1999 Nov-Dec;19(6C):5583-6
Increased survival in brain metastatic patients treated with stereotactic
radiotherapy, omega three fatty acids and bioflavonoids.
Gramaglia A, Loi GF, Mongioj V, Baronzio GF
National Cancer Institute, Milan, Italy.
Stereotactic radiotherapy represents a method to effectively treat brain
metastases with high precision and with high doses. Few acute toxicities
are
associated with stereotactic radiotherapy, however delayed reactions
may occur
and after six months, 20% of patients can develop radionecrosis. To
avoid this
adverse effect, in patients with metastases localized in critical brain
areas, a
supplementation of Omega three fatty acids and bioflavonoids has been
used. At
the end of 1997, we initiated a series of retrospective studies to
test the
efficacy of stereotactic radiotherapy on 405 patients, and the prognostic
importance on survival of various variables among which this type of
supplementation. From the comparison of various survival curves with
the Cox
multivariate analysis, it emerged that the patients using this supplementation
had a decreased risk ratio and an improvement in survival time. A decreased
number of radionecrosis was noted. We suggest their use as radioprotectors.
PMID: 10697622, UI: 20162730
3: J Nutr Sci Vitaminol (Tokyo) 1999 Oct;45(5):633-41
Depletion of dietary n-3 fatty acid affects the level of cyclic AMP
in rat
hippocampus.
Nanjo A, Kanazawa A, Sato K, Banno F, Fujimoto K
Department of Applied Biology and Chemistry, Faculty of Agriculture,
Tohoku
University, Sendai, Japan.
Prolonged depletion of dietary n-3 fatty acid induces a neurological
disturbance. To ascertain the deficit of neurotransmission at the time
of n-3
deficiency, the concentrations of cAMP and inositol triphosphate, and
the
activities of protein kinases A and C were examined in vitro in rat
hippocampus.
Furthermore, the saturation binding study of [3H]quinuclidinyl benzilate,
a
specific antagonist to muscarinic cholinergic receptor, was performed.
Rats were
fed a safflower oil diet as the deficient group and a soybean oil diet
as the
control group. Hippocampi were obtained from rats in the 3rd generation
in the
deficient group and in the 2nd generation in the control group. Dietary
effect
was not observed in the parameters except for the concentration of
cAMP, which
was significantly higher in the deficient group than in the control
group.
PMID: 10683814, UI: 20147438
4: Arch Tierernahr 1999;52(4):371-90
[The effect of palm oil and safflower oil in the feed of parent fattening
hens
on fertility, hatchability and growth of progeny].
[Article in German]
Halle I
Institut fur Tierernahrung, Bundesforschungsanstalt fur Landwirtschaft
(FAL),
Nauendorf/Merbitz, Germany.
The aim of two experiments with broiler breeder hens was to evaluate
the effect
of diets containing palm butter or safflower oil (25 g and 50 g/kg
feed, resp.)
on fertility, hatchability and growth of progeny. Especially the incorporation
of oleic and linoleic acid in egg yolk reflected the dietary fatty
acid source.
Eggs were collected and stored in the incubator at a hen age of 31,
40, 50, and
60 weeks. Hatched chicks were reared over 5 weeks. The number of fertile
eggs
(Experiment 1 and 2, 75 and 88%, resp.) differed between the experiments
(P < or
= 0.05). Neither embryonic mortality nor hatchability (Experiment 1
and 2, 76
and 78%, resp.) were significantly affected by fatty acid composition
of yolk.
No clear maternal dietary effect was recorded on chicken weight at
hatching
(Experiment 1 and 2, 43.3 g and 43.7 g, resp.) and at 35 days of age
(Experimental 1 and 2, 1676 g and 1764 g, resp.) The fatty acid composition
in
the analysed egg yolk sac of chicks showed a different fatty level
but
corresponded to fatty acid composition of breeding eggs before incubation.
According to a decreased level of docosahexaenoic acid in egg yolk
due to
increased incorporation of linoleic acid, the content of this fatty
acid was
also diminished in phospholipids of the brain of chicken on days 1
and 5 after
hatching.
PMID: 10674173, UI: 20139128
5: Adv Exp Med Biol 1999;469:647-53
Eicosapentaenoic acid alters manganese superoxide dismutase immunoreactive
protein levels in normal but not malignant central nervous system
derived cells.
Girnun GD, Oberley LW, Moore SA, Robbins ME
Radiation Research Laboratory, University of Iowa, Iowa City 52252, USA.
PMID: 10667394, UI: 20132046
6: Adv Exp Med Biol 1999;469:343-7
Formation of novel isoprostane-like compounds from docosahexaenoic acid.
Morrow JD, Tapper AR, Zackert WE, Yang J, Sanchez SC, Montine TJ, Roberts LJ
Department of Medicine, Vanderbilt University School of Medicine, Nashville,
TN
37232-6602, USA.
PMID: 10667351, UI: 20132003
7: Br J Nutr 1999 Sep;82(3):163-4
Modelling human infant requirements for long-chain polyunsaturated fatty acids.
Cunnane S
Department of Nutritional Sciences, University of Toronto, Canada.
PMID: 10655962, UI: 20121415
8: Lancet 1999 Dec 4;354(9194):1919-20
Long-chain polyunsaturated fatty acids and infant development.
Gibson RA
Child Nutrition Research Centre, Child Health Research Institute, Bedford
Park,
SA, Australia.
Publication Types:
Comment
Comments:
Comment on: Lancet 1999 Dec 4;354(9194):1948-54
Comment in: Lancet 2000 Mar 25;355(9209):1101-2
PMID: 10622289, UI: 20086001
9: Neuroscience 1999;94(1):305-14
Age-related changes in synaptic function: analysis of the effect
of dietary
supplementation with omega-3 fatty acids.
McGahon BM, Martin DS, Horrobin DF, Lynch MA
Department of Physiology, Trinity College, Dublin, Ireland.
Depolarization-induced transmitter release in synaptosomes prepared
from the
hippocampus of aged rats is decreased compared with release from young
animals.
Although the underlying cause of this deficit is not known, some evidence
suggests that increased membrane rigidity may contribute to these age-related
synaptic changes. One possible consequence of the decreased transmitter
release
in the hippocampus of aged rats is a reduced ability to sustain long-term
potentiation in perforant path-granule cell synapses, a pathway in
which
maintenance of long-term potentiation and increased glutamate release
have been
coupled. The observation that there is an age-dependent impairment
in long-term
potentiation is consistent with this view. If the age-related deficits
in
release and long-term potentiation are a consequence of increased membrane
rigidity, it must be predicted that any manoeuvre which reverses membrane
rigidity should reverse these functional deficits. In the present study,
we
investigated the effect of dietary manipulation of aged rats with omega-3
fatty
acids on synaptic function. The data obtained indicate that an eight-week
modified feeding schedule reversed the age-related impairments in long-term
potentiation and depolarization-induced glutamate transmitter release.
We also
report that the concentrations of both docosahexanoic acid and arachidonic
acid,
two main polyunsaturated fatty acids in neuronal membranes, were decreased
in
the hippocampus of aged rats, and were restored by dietary manipulation.
The
data are consistent with the hypothesis that these deficits results
from a
change in membrane composition.
PMID: 10613520, UI: 20078681
10: Lipids 1999 Nov;34(11):1177-86
Effects of postnatal ethanol exposure on brain growth and lipid composition
in
n-3 fatty acid-deficient and -adequate rats.
Ward GR, Xing HC, Wainwright PE
Department of Health Studies and Gerontology, University of Waterloo,
Ontario,
Canada. grward@healthy.uwaterloo.ca
The artificial rearing model was used to investigate the effects of
short-term
exposure to ethanol on growth and fatty acid composition of forebrain
(FB) and
cerebellum (CB) during the brain growth spurt in either n-3 fatty acid-adequate
(AD) or n-3 deficient (DEF) rat pups. On postnatal day 5, offspring
of female
rats that had been fed AD or DEF diets from day 5 of life were assigned
to three
groups: members of two groups were gastrostomized and artificially
fed formulas
appropriate for their maternal history, and the third group (suckled
control)
was fostered to lactating dams of a similar dietary history. Half of
the
artificially reared pups in each dietary condition were fed ethanol
in their
formula (7% vol/vol) in one-quarter of their daily feedings, while
the others
received maltose-dextrin substituted isocalorically for ethanol. Blood
alcohol
concentrations did not differ between the dietary groups. FB weight
on postnatal
day 9 was lower in ethanol-exposed offspring in both dietary conditions.
Brain
fatty acid composition reflected dietary history in that, compared
with AD pups,
DEF pups had lower percentages of docosahexaenoic acid, higher percentages
of
22:5n-6, and a higher n-6/n-3 fatty acid ratio. However, the effects
of ethanol
exposure were inconsistent, lowering the n-6/n-3 ratio in the
phosphatidylethanolamine (PE) fraction in FB but not in CB, while increasing
this ratio in the phosphatidylcholine (PC) fraction in FB of the DEF
pups only.
Thus, while ethanol had some effects on lipid composition, there was
no
difference between the dietary groups in their vulnerability to the
effects of
early short-term ethanol exposure on brain growth.
PMID: 10606040, UI: 20072056
11: Lipids 1999 Oct;34(10):1057-63
Effects of gamma-linolenic acid and docosahexaenoic acid in formulae
on brain
fatty acid composition in artificially reared rats.
Ward GR, Huang YS, Xing HC, Bobik E, Wauben I, Auestad N, Montalto M,
Wainwright
PE
Department of Health Studies and Gerontology, University of Waterloo,
Ontario,
Canada. grward@healthy.uwaterloo.ca
This study evaluated the effects of dietary supplementation with gamma-linolenic
acid (GLA, 18:3n-6) and docosahexaenoic acid (DHA, 22:6n-3) on the
fatty acid
composition of the neonatal brain in gastrostomized rat pups reared
artificially
from days 5-18. These pups were fed rat milk substitutes containing
fats that
provided 10% linoleic acid and 1% alpha-linolenic acid (% fatty acids)
and,
using a 2x3 factorial design, one of two levels of DHA (0.5 and 2.5%),
and one
of three levels of GLA (0.5, 1.0, and 3.0%). A seventh artificially
reared group
served as a reference group and was fed 0.5% DHA and 0.5% arachidonic
acid (AA,
20:4n-6); these levels are within the range of those found in rat milk.
The
eighth group, the suckled control group, was reared by nursing dams
fed a
standard American Institute of Nutrition 93M chow. The fatty acid composition
of
the phosphatidylethanolamine, phosphatidylcholine, and
phosphatidylserine/phosphatidylinositol membrane fractions of the forebrain
on
day 18 reflected the dietary composition in that high levels of dietary
DHA
resulted in increases in DHA but decreases in 22:4n-6 and 22:5n-6 in
brain. High
levels of GLA increased 22:4n-6 but, in contrast to previous findings
with high
levels of AA, did not decrease levels of DHA. These results suggest
that dietary
GLA, during development, differs from high dietary levels of AA in
that it does
not lead to reductions in brain DHA.
PMID: 10580333, UI: 20046278
12: Arch Biochem Biophys 1999 Oct 15;370(2):300-7
Biosynthesis and inactivation of N-arachidonoylethanolamine (anandamide)
and
N-docosahexaenoylethanolamine in bovine retina.
Bisogno T, Delton-Vandenbroucke I, Milone A, Lagarde M, Di Marzo V
Istituto per la Chimica Molecole di Interesse Biologico, CNR, Arco Felice,
Napoli, Italy.
N-Arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol
(2-AG),
the two proposed endogenous agonists of cannabinoid receptors, and
the putative
AEA biosynthetic precursor, N-arachidonoylphosphatidylethanolamine
(NArPE), were
identified in bovine retina by means of gas chromatography-electron
impact mass
spectrometry (GC-EIMS). This technique also allowed us to identify
N-docosahexanoylethanolamine (DHEA) and 2-docosahexanoylglycerol (2-DHG),
two
derivatives of docosahexaenoic acid (DHA), one of the most abundant
fatty acids
esterified in retina phospholipids and necessary for optimal retinal
function.
N-Docosahexaenoylphosphatidylethanolamine (NDHPE), the potential biosynthetic
precursor for DHEA, was also found. The fatty acid composition of the
sn-1 and
sn-2 positions of bovine retina's most abundant phospholipid classes,
also
determined here, were in agreement with a phospholipid-dependent mechanism
for
2-AG, 2-DHG, AEA, and DHEA biosynthesis, as very high levels of polyunsaturated
fatty acids, including DHA, were found on the sn-2 position of
phosphatidylcholine (PC) and -ethanolamine (PE), and measurable amounts
of
di-docosahexanoyl-PC and -PE, two potential biosynthetic precursors
of NDHPE,
were detected. Accordingly, we found that isolated particulate fractions
from
bovine retina could release AEA and DHEA in a time-dependent fashion.
Finally, a
fatty acid amide hydrolase (FAAH)-like activity with subcellular distribution
and pH dependency similar to those reported for the brain enzyme was
also
detected in bovine retina. This activity was inhibited by FAAH inhibitors,
phenylmethylsulfonyl fluoride and arachidonoyltrifluoromethylketone,
and
appeared to recognize DHEA with a lower efficiency than AEA. These
data indicate
that AEA and its congeners may play a physiological role in the mammalian
eye.
PMID: 10577359, UI: 20021245
13: J Membr Biol 1999 Nov 1;172(1):1-11
The antiarrhythmic and anticonvulsant effects of dietary N-3 fatty acids.
Leaf A, Kang JX, Xiao YF, Billman GE, Voskuyl RA
Departments of Medicine, Massachusetts General Hospital, Bldg 149, 13th
Street,
Charlestown, MA 02129, USA.
It has been shown in animals and probably in humans, that n-3 polyunsaturated
fatty acids (PUFAs) are antiarrhythmic. We report recent studies on
the
antiarrhythmic actions of PUFAs. The PUFAs stabilize the electrical
activity of
isolated cardiac myocytes by modulating sarcolemmal ion channels, so
that a
stronger electrical stimulus is required to elicit an action potential
and the
refractory period is markedly prolonged. Inhibition of voltage-dependent
sodium
currents, which initiate action potentials in excitable tissues, and
of the
L-type calcium currents, which initiate release of sarcoplasmic calcium
stores
that increase cytosolic free calcium concentrations and activate the
contractile
proteins in myocytes, appear at present to be the probable major antiarrhythmic
mechanism of the PUFAs.
Publication Types:
Review
Review, tutorial
PMID: 10552009, UI: 20020315
14: J Nutr 1999 Nov;129(11):2088-93
Docosahexaenoic and arachidonic acid prevent a decrease in dopaminergic
and
serotoninergic neurotransmitters in frontal cortex caused by a linoleic
and
alpha-linolenic acid deficient diet in formula-fed piglets.
de la Presa Owens S, Innis SM
Department of Paediatrics, University of British Columbia, Vancouver,
Canada V5Z
4H4.
This study examined the effects of diets deficient (D) in linoleic [18:2(n-6)]
and linolenic acid [18:3(n-3)] at 0.8 and 0.05% energy, respectively,
or
adequate (C) in 18:2(n-6) and 18:3(n-3) at 8.3 and 0.8% energy, respectively,
without (-) or with (+) 0.2% energy arachidonic [20:4(n-6)] and 0.16%
energy
docosahexaenoic [22:6(n-3)] acid in piglets fed from birth to 18 d.
Frontal
cortex dopaminergic and serotoninergic neurotransmitters and phospholipid
fatty
acids were measured. Piglets fed the D- diet had significantly lower
frontal
cortex dopamine, 3,4-dihydroxyphenylacetic (DOPAC), homovanillic acid
(HVA),
serotonin and 5-hydroxyindoleacetic acid (5-HIAA) concentrations than
did
piglets fed the C- diets. Frontal cortex dopamine, norepinephrine,
DOPAC, HVA,
serotonin and 5-HIAA were higher in piglets fed the D+ compared to
those fed the
D- diet (P < 0.05) and not different between piglets fed the D+
and those fed
the C- diets or the C- and C+ diets. Piglets fed the D- diet had lower
frontal
cortex phosphatidylcholine (PC) and phosphatidylinositol (PI) 20:4(n-6)
and PC
and phosphatidylethanolamine (PE) 22:6(n-3) than did piglets fed the
C- diet (P
< 0.05). Piglets fed the D+ diet had higher frontal cortex PC and
PI 20:4(n-6)
and PC, PE, PS and PI 22:6(n-3) than did piglets fed the D- diet. These
studies
show that dietary essential fatty acid deficiency fed for 18 d from
birth
affects frontal cortex neurotransmitters in rapidly growing piglets
and that
these changes are specifically due to 20:4(n-6) and/or 22:6(n-3).
PMID: 10539789, UI: 20007868
15: J Nutr 1999 Nov;129(11):2074-80
Dietary docosahexaenoic acid-enriched phospholipids normalize urinary
melatonin
excretion in adult (n-3) polyunsaturated fatty acid-deficient rats.
Zaouali-Ajina M, Gharib A, Durand G, Gazzah N, Claustrat B, Gharib C, Sarda N
Laboratoire de Physiologie de l'Environnement, Faculte de Medecine Lyon
Grange-Blanche, 69373 Lyon Cedex 08, France.
Melatonin (MEL) plays an essential role in physiologic functions associated
with
darkness. We examined the effects of docosahexaenoic acid (DHA)-enriched
phospholipids from pig brains (BPL) or hen eggs (EPL), as sources of
DHA, on
lipid FA composition of pineal membranes and daytime and nighttime
concentrations of 6-sulfatoxymelatonin (aMT6) in adult male control
and
(n-3)-deficient rats fed BPL and EPL diets for 5 wk. In two experiments,
at 3 wk
of age, rats were divided into subgroups and fed semipurified diets
containing
either peanut oil [(n-3)-deficient group] or peanut plus rapeseed oil
(control
group) and two dietary formulas containing either 3.5 g/100 g diet
of BPL
(Experiment 1) or 5.0 g/100 g diet of EPL (Experiment 2). BPL and EPL
diets
provided approximately 200 mg of DHA/100 g diet. During the daytime,
aMT6
concentrations were not significantly different among groups. Conversely,
the
(n-3)-deficient rats had significantly lower nighttime aMT6 concentrations
than
the control rats. BPL and EPL did not affect urinary nighttime aMT6
concentration in the control group, whereas (n-3)-deficient + BPL or
EPL groups
exhibited significantly higher nighttime aMT6 concentrations than the
(n-3)-deficient group (76 and 110%, respectively). The level of DHA
was
significantly higher in the pineal glands of control rats than in
(n-3)-deficient rats. In rats fed EPL and BPL, the level of DHA reached
a
plateau, between 10 and 11 mg/100 mg total fatty acids in control +
BPL or EPL
and (n-3)-deficient + BPL or EPL groups. These findings suggest that
new
DHA-enriched formulas may be used as an efficient alternative source
of (n-3)
polyunsaturated fatty acids to normalize MEL secretion.
PMID: 10539787, UI: 20007866
16: Brain Res 1999 Oct 30;846(1):112-21
Polyunsaturated fatty acids modify mouse hippocampal neuronal excitability
during excitotoxic or convulsant stimulation.
Xiao Y, Li X
The Charles A. Dana Research Institute and The Harvard-Thorndike Laboratory,
Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston,
MA 02215,
USA. yxiao@bidmc.harvard.edu
The n-3 polyunsaturated fatty acids (PUFAs) reduce cardiac membrane
excitability
and prevent cardiac arrhythmias in animals and probably in humans.
In this
study, we assessed the effects of n-3 PUFAs on membrane excitability
in mouse
hippocampal neurons with both whole-cell current and voltage-clamp
methods.
Extracellular application of 20 microM eicosapentaenoic acid (EPA,
C20:5n-3)
significantly reduced the frequency of electrical-evoked action potentials
in
CA1 neurons of hippocampal slices from 3.8+/-0.7 Hz of control to 2.1+/-0.5
Hz.
In addition, EPA significantly hyperpolarized the resting membrane
potential and
raised the stimulatory threshold of action potentials in CA1 neurons.
Another
n-3 PUFA, docosahexaenoic acid (DHA, C22:6n-3), had effects on membrane
excitability similar to those of EPA. In contrast, EPA ethyl ester,
oleic acid
(OA, C18:n-9), and stearic acid (SA, C18:0) did not alter the membrane
excitability in CA1 neurons. Bath application of pentylenetetrazole
(PTZ) or
glutamate reduced the stimulatory threshold and increased the frequency
of
action potentials of hippocampal neurons. EPA restored PTZ- or
glutamate-enhanced neuronal excitability to the control level. EPA
also
suppressed glutamate-activated inward currents. Furthermore, EPA and
DHA
significantly inhibited the frequency of action potentials without
effecting the
stimulatory threshold of CA3 neurons. These data demonstrate that n-3
PUFAs
modify neuronal membrane excitability under control and drug-stimulated
conditions. The sensitivity to these effects of PUFAs varies from neurons
of
different hippocampal regions.
PMID: 10536218, UI: 20007756
17: Brain Res 1999 Oct 2;843(1-2):184-92
Influence of dietary fats on c-Fos-like immunoreactivity in mouse hypothalamus.
Wang H, Storlien LH, Huang XF
Metabolic Research Center, Department of Biomedical Science, University
of
Wollongong, Wollongong, Australia.
The hypothalamus is a brain region of major importance in regulation
of energy
balance via autonomic nervous control of both intake and expenditure.
There is
substantial evidence that diets high in saturated fats lead to obesity
while
diets equally high in polyunsaturated fats (PUFAs) do not. Using c-Fos
as a
marker, this study aimed to investigate hypothalamic neuronal response
in mice
fed high fat diets (58% of calories as fat) emphasising saturated,
n-3 or n-6
polyunsaturated fatty acids, or a low fat (10% of calories) diet over
periods of
1 and 7 weeks. In addition, a 4-week "reversal" intervention with n-3
polyunsaturated or low fat diet was undertaken in saturated fat-fed
mice. Food
intake and body weight were measured over the feeding periods. At 1,
7 and 11
weeks mice were killed, epididymal fat pad were weighed and brains
were removed
for quantitation of hypothalamic c-Fos-like immunoreactive (FLI) neurons.
Weight
gain, and epididymal fat pad weight, were highest on the saturated
fat diet and
lowest on the n-3 diet despite similar food intakes (epididymal fat
weight at
week 7: saturated fat, 622+/-48 mg; n-6 fat 423+/-69; low fat 387+/-10,
n-3 fat
225+/-26). Compared to a low fat diet, FLI neurons in the dorsal part
of lateral
hypothalamic (dLH) area was dramatically increased by saturated fat
feeding
(+367% at 1 week) while ventromedial hypothalamic (VMH) activity was
decreased.
In contrast with n-6 and n-3 feeding dLH FLI neuronal activity was
unchanged but
actually increased in the VMH. Paraventricular nucleus (PVN) FLI neurons
increased in the high saturated group only at 7 and 11 weeks, after
substantial
fat accumulation. Substitution of saturated fat diet with the n-3 diet
partially
reversed (48%) the increase in FLI neurons in PVN of saturated fat-fed
mice,
while it significantly increase FLI neurons in arcuate nucleus (+400%).
In
summary, this study demonstrates that dietary saturated fat modulates
hypothalamic neuronal activity in a pattern (high lateral, reduced
ventromedial
activity) consistent with its obesogenic effects. In contrast, diets
equally
high in PUFA (particularly of the n-3 class) neither increase adiposity
nor
derange the lateral/medial neuronal activity balance.
PMID: 10528124, UI: 99458795
18: Biol Pharm Bull 1999 Aug;22(8):775-9
Long-term n-3 fatty acid deficiency induces no substantial change
in the rate of
protein synthesis in rat brain and liver.
Sato A, Osakabe T, Ikemoto A, Watanabe S, Kobayashi T, Okuyama H
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences,
Nagoya
City University, Nagoya, Japan.
The influence of long-term n-3 fatty acid deficiency on the rate of
protein
synthesis in rat brain and liver was investigated in relation to learning
behavior or a presumed survival time-shortening factor (SSF) in rapeseed
oil,
using a large-dose [3H]phenylalanine (Phe) injection method. When Wistar
rats
were made n-3 fatty acid-deficient by feeding a safflower oil
(alpha-linolenate-deficient) diet for 2 generations, conditions under
which the
safflower oil group had been shown to exhibit altered learning behaviors,
compared with the perilla oil group, no significant changes in the
rate of
protein synthesis were observed compared with the perilla oil
(alpha-linolenate-sufficient) or rapeseed oil (alpha-linolenate-sufficient
but
SSF-containing) groups. However, the rapeseed oil group had a reduced
specific
radioactivity of free Phe in the cerebral cortex, compared with the
safflower
oil group. In contrast to the reported observation of very long-term
n-3 fatty
acid deficiency inducing an almost 2-fold increase in the rate of protein
synthesis in the brain, our results indicate that altered learning
behavior
resulting from n-3 fatty acid deficiency in rats is not associated
with any
substantial changes in the rate of protein synthesis in the brain.
PMID: 10480312, UI: 99408189
19: Pharmacol Res 1999 Sep;40(3):211-25
Health benefits of docosahexaenoic acid.
Horrocks LA, Yeo YK
Docosa Foods Ltd, 1275 Kinnear Road, Columbus, OH 43212-1155, USA,
Docosahexaenoic acid (DHA) is essential for the growth and functional
development of the brain in infants. DHA is also required for maintenance
of
normal brain function in adults. The inclusion of plentiful DHA in
the diet
improves learning ability, whereas deficiencies of DHA are associated
with
deficits in learning. DHA is taken up by the brain in preference to
other fatty
acids. The turnover of DHA in the brain is very fast, more so than
is generally
realized. The visual acuity of healthy, full-term, formula-fed infants
is
increased when their formula includes DHA. During the last 50 years,
many
infants have been fed formula diets lacking DHA and other omega-3 fatty
acids.
DHA deficiencies are associated with foetal alcohol syndrome, attention
deficit
hyperactivity disorder, cystic fibrosis, phenylketonuria, unipolar
depression,
aggressive hostility, and adrenoleukodystrophy. Decreases in DHA in
the brain
are associated with cognitive decline during aging and with onset of
sporadic
Alzheimer disease. The leading cause of death in western nations is
cardiovascular disease. Epidemiological studies have shown a strong
correlation
between fish consumption and reduction in sudden death from myocardial
infarction. The reduction is approximately 50% with 200 mg day(-1)of
DHA from
fish. DHA is the active component in fish. Not only does fish oil reduce
triglycerides in the blood and decrease thrombosis, but it also prevents
cardiac
arrhythmias. The association of DHA deficiency with depression is the
reason for
the robust positive correlation between depression and myocardial infarction.
Patients with cardiovascular disease or Type II diabetes are often
advised to
adopt a low-fat diet with a high proportion of carbohydrate. A study
with women
shows that this type of diet increases plasma triglycerides and the
severity of
Type II diabetes and coronary heart disease. DHA is present in fatty
fish
(salmon, tuna, mackerel) and mother's milk. DHA is present at low levels
in meat
and eggs, but is not usually present in infant formulas. EPA, another
long-chain
n-3 fatty acid, is also present in fatty fish. The shorter chain n-3
fatty acid,
alpha-linolenic acid, is not converted very well to DHA in man. These
longchain
n-3 fatty acids (also known as omega-3 fatty acids) are now becoming
available
in some foods, especially infant formula and eggs in Europe and Japan.
Fish oil
decreases the proliferation of tumour cells, whereas arachidonic acid,
a
longchain n-6 fatty acid, increases their proliferation. These opposite
effects
are also seen with inflammation, particularly with rheumatoid arthritis,
and
with asthma. DHA has a positive effect on diseases such as hypertension,
arthritis, atherosclerosis, depression, adult-onset diabetes mellitus,
myocardial infarction, thrombosis, and some cancers. Copyright 1999
Academic
Press.
Publication Types:
Review
Review, tutorial
Comments:
Comment in: Pharmacol Res 1999 Sep;40(3):203
Comment in: Pharmacol Res 1999 Sep;40(3):205-6
PMID: 10479465, UI: 99410600
20: Am J Clin Nutr 1999 Sep;70(3 Suppl):555S-559S
Essential fatty acid requirements of vegetarians in pregnancy, lactation,
and
infancy.
Sanders TA
Nutrition, Food and Health Research Centre, King's College London, United
Kingdom. Tom.Sanders@kcl.ac.uk
Long-chain polyunsaturated fatty acids (LCPUFAs) derived from linoleic
(18:2n-6)
and alpha-linolenic (18:3n-3) acids are required for the normal development
of
the retina and central nervous system, but the extent to which they
can be
synthesized from the parent fatty acids is debated. Consuming LCPUFAs
markedly
increases their proportions in tissue lipids compared with their parent
fatty
acids. Thus, it has been argued that LCPUFAs must be supplied in the
diet.
LCPUFAs are generally absent from plant foods, thus it is important
find out how
essential fatty acid requirements are met by vegetarians. A developing
fetus
obtains LCPUFAs via selective uptake from its mother's plasma and LCPUFAs
are
present in the breast milk of vegetarians. There is no evidence that
the
capacity to synthesize LCPUFAs is limited in vegetarians. However,
there are
greater proportions of n-6 LCPUFAs and lower proportions of n-3 LCPUFAs
in
vegetarians compared with omnivores. This difference is probably a
consequence
of the selection of foods by vegetarians with high amounts of linoleic
acid.
Although lower concentrations of docosahexaenoic acid (22:6n-3; DHA)
have been
observed in blood and artery phospholipids of infants of vegetarians,
it is
uncertain whether their brain lipids contain lower proportions of DHA
than do
those of infants of omnivores. On the basis of experiments in primates
that
showed altered visual function with a high ratio of linoleic acid to
alpha-linolenic acid, it would be prudent to recommend diets with a
ratio
between 4:1 and 10:1 in vegetarians and that excessive intakes of linoleic
acid
be avoided.
Publication Types:
Review
Review, tutorial
PMID: 10479231, UI: 99408696
21: Prostaglandins Leukot Essent Fatty Acids 1999 May-Jun;60(5-6):387-92
Carbon recycling into de novo lipogenesis is a major pathway in neonatal
metabolism of linoleate and alpha-linolenate.
Cunnane SC, Menard CR, Likhodii SS, Brenna JT, Crawford MA
Department of Nutritional Sciences, Faculty of Medicine, University
of Toronto,
Canada. s.cunnane@utoronto.ca
Recent reports indicate that recycling of the beta-oxidized carbon skeleton
of
linoleate and alpha-linolenate into newly synthesized cholesterol and
fatty
acids in the brain is quantitatively significant in both suckling rats
and pre-
and postnatally in rhesus monkeys. The recycling appears to occur via
ketones
which are not only readily produced from these 18 carbon polyunsaturates
but are
also the main lipogenic precursors for the developing mammalian brain.
Since the
neonatal rat brain appears not to acquire cholesterol or long chain
saturated or
monounsaturated fatty acids from the circulation, ketones and ketogenic
precursors seem to be crucial for normal brain synthesis of these lipids.
Cholesterol is plentiful in brain membranes and it has also been discovered
to
be the essential lipid adduct of the 'hedgehog' family of proteins,
the
appropriate expression of which determines normal embryonic tissue
patterning
and neurological development. Insufficient cholesterol or inappropriate
expression of 'sonic hedgehog' has major adverse neurodevelopmental
consequences
typified in humans by Smith-Lemli-Optiz syndrome. Hence, we propose
that the
importance of alpha-linolenate and linoleate for normal neural development
arises not only from being precursors to longer chain polyunsaturates
incorporated into neuronal membranes but, perhaps equally importantly,
by being
ketogenic precursors needed for in situ brain lipid synthesis.
Publication Types:
Review
Review, tutorial
PMID: 10471127, UI: 99397728
22: Anticancer Res 1999 May-Jun;19(3A):2041-8
Tissue distribution and metabolism of gamma-linolenoyl-3-eicosapentaenoyl
propane diol enterally or intravenously administered to mice bearing
human
pancreatic carcinomas.
De Antueno R, Bai M, Elliot M
Scotia Research Institute, Kentville, NS, Canada. r.deantueno@mailexcite.com
Synthetic propane diol lipids have been proposed as novel compounds
to deliver
cytocidal polyunsaturated fatty acids (PUFA) such as gamma-linolenic
(GLA) and
eicosapentaenoic (EPA) acids. To assess the biodistribution and metabolism
of
these PUFA in immunodeficient mice bearing human pancreatic carcinomas
(AsPC-1),
gamma-linolenoyl-3-eicosapentaenoyl propane diol (GE diol) was provided
in a
fat-free diet (5% w:w) for 6 weeks or parentally administered as 14C-GE
diol (1
or 3 consecutive doses of 1.66 g/kg/day) in an innovative
non-ionic-digalactosyldiacylglycerol emulsion. In tumor, liver, brain,
kidney,
plasma and fat tissue of mice fed GE diol, PUFA were increased over
25-fold,
except for arachidonic acid (AA) levels, which were reduced or remained
constant
when compared to mice fed control corn oil diet. GLA and EPA were mainly
stored
in fat tissue. The recovery of radioactivity from the i.v. infected
14C-GE diol
was dose and time dependent. Ten days after the i.v. infusion, GLA
was only
detected in substantial concentrations in tumor and in fat tissue (21
and 202
micrograms/g, respectively). Overall, these studies showed that: GE
diol
emulsions provide 640-fold higher doses of both GLA and EPA without
causing
hemolysis or adverse effects in the host mouse when compared to free
PUFA
infusions; GE diol is metabolized after oral or i.v. administration;
tumor
concentrations of GLA and EPA from the enterally administered diol
were 4 to
13-fold higher than the in vitro cytotoxic levels; EPA, competes with
AA and
probably inhibits the activity of delta 5 desaturase without affecting
the
elongation of GLA in the host and tumor tissue; the change in PUFA
profile
modifies the substrates for eicosanoid synthesis. In short, a potentially
desirable cytotoxic PUFA pattern can be achieved in host tissues and,
in
particular, in a human pancreatic tumor by providing GLA and EPA in
the form
GE-diol. These findings guarantee further investigations in oncology
with this
neutral diol lipid.
PMID: 10470146, UI: 99399132
23: Neuroscience 1999;93(1):237-41
Chronic administration of docosahexaenoic acid improves reference
memory-related
learning ability in young rats.
Gamoh S, Hashimoto M, Sugioka K, Shahdat Hossain M, Hata N, Misawa Y, Masumura S
Department of Physiology, Shimane Medical University, Izumo, Japan.
Wistar rats were fed a fish oil-deficient diet through three generations.
The
young (five-week-old) male rats of the third generation were randomly
divided
into two groups. Over 10 weeks, one group was perorally administered
docosahexaenoic acid dissolved in 5% gum Arabic solution at 300 mg/kg/day;
the
other group received a similar volume of vehicle alone. Five weeks
after
starting the administration, the rats were tested for learning ability
related
to two types of memory, reference memory and working memory, with the
partially
(four of eight) baited eight-arm radial maze. Reference memory is information
that should be retained until the next trial. Working memory is information
that
disappears in a short time. Entries into unbaited arms and repeated
entries into
visited arms were defined as reference memory errors and working memory
errors,
respectively. Docosahexaenoic acid administration over 10 weeks significantly
reduced the number of reference memory errors, without affecting the
number of
working memory errors, and significantly increased the docosahexaenoic
acid
content and the docosahexaenoic acid/arachidonic acid ratio in both
the
hippocampus and the cerebral cortex. In addition, the ratio demonstrated
a
significantly negative correlation with the number of reference memory
errors.
These results suggest that chronic administration of docosahexaenoic
acid is
conducive to the improvement of reference memory-related learning ability,
and
that the docosahexaenoic acid/arachidonic acid ratio in the hippocampus
or the
cerebral cortex, or both, may be an indicator of learning ability.
PMID: 10430487, UI: 99357566
24: J Lipid Res 1999 Aug;40(8):1501-5
An octaene fatty acid, 4,7,10,13,16,19,22,25-octacosaoctaenoic acid
(28:8n-3),
found in marine oils.
Van Pelt CK, Huang MC, Tschanz CL, Brenna JT
Division of Nutritional Sciences, 116 Savage Hall, Cornell University,
Ithaca,
NY 14853-6301, USA.
We report structure determination of an octaene fatty acid, 4,7,10,
13,16,19,22,25-octacosaoctaenoic acid (28:8n-3). The molecular weight
and double
bond locations were determined using acetonitrile chemical ionization
mass
spectrometry (MS) and MS/MS and were confirmed by MS of hydrogenated
and
deuterogenated 28:8 and by argentation thin-layer chromatography. 28:8n-3
was
1.2 +/- 0.1%, in oil derived from the heterotrophic dinoflagellate
Crypthecodinium cohnii and a commercial polyunsaturated fatty acid
concentrate
derived from fish oils (0.16 +/- 0.01%), both components of human dietary
supplements. It was not found in whole bovine retina, cultured Y79
human
retinoblastoma cells, or neonate baboon cerebral cortex. The long chain
polyunsaturates present in the C. cohnii oil suggest a possible route
for
28:8n-3 biosynthesis similar to that for biosynthesis of 22:6n-3.
PMID: 10428987, UI: 99359511
25: Lipids 1999;34 Suppl:S347-50
Dietary 18:3n-3 and 22:6n-3 as sources of 22:6n-3 accretion in neonatal
baboon
brain and associated organs.
Su HM, Bernardo L, Mirmiran M, Ma XH, Nathanielsz PW, Brenna JT
Division of Nutritional Sciences, Cornell University, Ithaca, New York
14853,
USA.
The bioequivalence of dietary linolenic acid (LNA) and docosahexaenoic
acid
(DHA) for brain DHA accretion was measured in neonatal baboons at 4-6
wk of age
using stable isotope tracers. Neonates consumed a conventional U.S.
term-infant
formula devoid of long chain polyunsaturates and with an n-6/n-3 ratio
of about
10:1. At 4 wk of age, neonates were dosed with either 13C LNA or 13C
DHA. At 6
wk of age, neonate brain, retina, and other organs were harvested for
fatty acid
and isotopic analyses. The relative accretion of labeled DHA was 7-fold
greater
as a percentage of dose for the DHA-dosed animals compared to the LNA-dosed
animals. The baboon is an omnivore that regularly consumes meat and
insects; its
plasma lipid profile responds similarly to humans in response to changes
in
feeding and living habits. These observations suggest that the baboon
is a
suitable model for human unsaturated fatty acid studies.
PMID: 10419199, UI: 99345567
26: Lipids 1999;34 Suppl:S251
n-3 polyunsaturated fatty acid deficiency and dopamine metabolism
in the rat
frontal cortex.
Zimmer L, Durand G, Guilloteau D, Chalon S
INSERM U316, Tours, France.
PMID: 10419169, UI: 99345537
27: Lipids 1999;34 Suppl:S249-50
The role of docosahexaenoic acid (22:6n-3) in neuronal signaling.
Kim HY, Edsall L
Laboratory of Membrane Biochemistry and Biophysics, National Institute
on
Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville,
Maryland
20852, USA. hykim@nih.gov
PMID: 10419168, UI: 99345536
28: Lipids 1999;34 Suppl:S247-8
Ethyl docosahexaenoic acid administration during intrauterine life
enhances
prostanoid production and reduces free radicals generation in the
fetal rat
brain.
Glozman S, Green P, Kamensky B, Weiner L, Yavin E
Department of Neurobiology, Weizmann Institute, Rehovot, Israel.
PMID: 10419167, UI: 99345535
29: Lipids 1999;34 Suppl:S239-43
Rats with low levels of brain docosahexaenoic acid show impaired
performance in
olfactory-based and spatial learning tasks.
Greiner RS, Moriguchi T, Hutton A, Slotnick BM, Salem N Jr
Laboratory of Membrane Biochemistry and Biophysics, National Institute
on
Alcohol Abuse and Alcoholism, Division on Intramural Clinical and Biological
Research, Rockville, Maryland 20852, USA. nsalem@niaaa.nih.gov
Studies were carried out to determine if decreased levels of central
nervous
system docosahexaenoic acid (DHA), a result of consuming an n-3-deficient
diet,
had an effect on learning- and memory-related behaviors in adult male
rats.
Females were reared on an n-3-deficient or n-3-adequate diet beginning
at 21 d
of life. Their male pups, the F2 generation, were weaned to the diet
of the dam
and tested at 9-12 wk of age. An olfactory-based discrimination and
Morris water
maze task were used to assess performance. Whole brain was collected
after the
behavioral experiments and central nervous system fatty acid content
was
analyzed in olfactory bulb total lipid extracts. F2 generation male
rats
consuming the n-3-deficient diet had an 82% decrease in DHA compared
to rats
consuming the n-3-adequate diet. The n-3-deficient animals made significantly
more total errors in a 7-problem, 2-odor discrimination task compared
to the
n-3-adequate group. Furthermore, the escape latency in the Morris water
maze
task was significantly longer for the n-3-deficient rats compared to
the
n-3-adequate rats. These results indicate that rats with decreased
DHA levels in
the central nervous system perform poorer in these tasks compared to
rats with
higher DHA levels and suggest the presence of learning deficits in
these
animals.
PMID: 10419165, UI: 99345533
30: Lipids 1999;34 Suppl:S117
A role for cerebral and retinal endothelial cells in the supply of
docosahexaenoic acid to the brain and the retina?
Delton-Vandenbroucke I, Grammas P, Anderson RE
Department of Ophthalmology, Oklahoma Center for Neuroscience, University
of
Oklahoma Health Sciences Center, Oklahoma City, USA.
PMID: 10419115, UI: 99345483
31: Lipids 1999;34 Suppl:S39-47
Evidence for the unique function of docosahexaenoic acid during the
evolution of
the modern hominid brain.
Crawford MA, Bloom M, Broadhurst CL, Schmidt WF, Cunnane SC, Galli C,
Gehbremeskel K, Linseisen F, Lloyd-Smith J, Parkington J
Institute of Brain Chemistry, London, United Kingdom.
michael@macrawf.demon.co.uk
The African savanna ecosystem of the large mammals and primates was
associated
with a dramatic decline in relative brain capacity associated with
little
docosahexaenoic acid (DHA), which is required for brain structures
and growth.
The biochemistry implies that the expansion of the human brain required
a
plentiful source of preformed DHA. The richest source of DHA is the
marine food
chain, while the savanna environment offers very little of it. Consequently
Homo
sapiens could not have evolved on the savannas. Recent fossil evidence
indicates
that the lacustrine and marine food chain was being extensively exploited
at the
time cerebral expansion took place and suggests the alternative that
the
transition from the archaic to modern humans took place at the land/water
interface. Contemporary data on tropical lakeshore dwellers reaffirm
the above
view with nutritional support for the vascular system, the development
of which
would have been a prerequisite for cerebral expansion. Both arachidonic
acid and
DHA would have been freely available from such habitats providing the
double
stimulus of preformed acyl components for the developing blood vessels
and
brain. The n-3 docosapentaenoic acid precursor (n-3 DPA) was the major
n-3-metabolite in the savanna mammals. Despite this abundance, neither
it nor
the corresponding n-6 DPA was used for the photoreceptor nor the synapse.
A
substantial difference between DHA and other fatty acids is required
to explain
this high specificity. Studies on fluidity and other mechanical features
of cell
membranes did not reveal a difference of such magnitude between even
alpha-linolenic acid and DHA sufficient to explain the exclusive use
of DHA. We
suggest that the evolution of the large human brain depended on a rich
source of
DHA from the land/water interface. We review a number of proposals
for the
possible influence of DHA on physical properties of the brain that
are essential
for its function.
Publication Types:
Review
Review, tutorial
PMID: 10419087, UI: 99345455
32: Eur J Pharmacol 1999 May 14;372(2):167-74
Delayed administration of ethyl eicosapentate improves local cerebral
blood flow
and metabolism without affecting infarct volumes in the rat focal
ischemic
model.
Katsumata T, Katayama Y, Obo R, Muramatsu H, Ohtori T, Terashi A
Second Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
The objective of this study was to assess whether delayed administration
of
ethyl eicosapentate has a favorable effect on cerebral blood flow and
metabolism
in rats suffering from cerebral infarction. Adult male Sprague-Dawley
rats
weighing 250-300 g were used. Left middle cerebral artery occlusion
was induced
for 2 h. After 24-h reperfusion, rats were treated with ethyl eicosapentate
(100
mg kg(-1); ethyl eicosapentate treated) or saline (saline treated)
by gavage,
once a day for 4 weeks. After 4 weeks, local cerebral blood flow and
local
cerebral glucose utilization were measured autoradiographically, and
infarction
size was measured. In the ischemic side, the local cerebral blood flow
and local
cerebral glucose utilization values in the parietal cortex and the
lateral
caudoputamen, which constituted the ischemic core, were equivalent
to zero in
both groups. The peri-infarcted areas, i.e., the frontal cortex and
medial
caudoputamen, were significantly higher in the ethyl eicosapentate
treated group
than the saline treated group. In the non-ischemic side, ethyl eicosapentate
treated group had a tendency to improve local cerebral blood flow and
local
cerebral glucose utilization values in a medial caudoputamen. These
results
suggest that ethyl eicosapentate treatment may be beneficial for maintaining
cerebral circulation and metabolism except for infarction area after
cerebral
infarction.
PMID: 10395096, UI: 99321019
33: Lipids 1999 May;34(5):475-82
The effects of dietary alpha-linolenic acid compared with docosahexaenoic
acid
on brain, retina, liver, and heart in the guinea pig.
Abedin L, Lien EL, Vingrys AJ, Sinclair AJ
Department of Food Science, Royal Melbourne Institute of Technology
University,
Victoria, Australia.
The aim of this study was to compare two different strategies to elevate
brain,
retina, liver, and heart docosahexaenoic acid (DHA) levels in guinea
pigs.
First, we used an increasing dose of alpha-linolenic acid (ALA) relative
to a
constant linoleic acid (LA) intake, and second, we used two levels
of dietary
DHA provided in conjunction with dietary arachidonic acid (AA). The
percentage
DHA and AA of total phospholipids in retina, liver, and heart, and
in the brain
phosphatidylethanolamine and phosphatidylcholine was studied in female
pigmented
guinea pigs (3 wk old) fed one of five semisynthetic diets containing
10% (w/w)
lipid for 12 wk. The LA content in the diets was constant (17% of total
fatty
acids), with the ALA content varying from 0.05% (diet SFO), to 1% (diet
Mix),
and to 7% (diet CNO). Two other diets (LCP1 and LCP3) had a constant
LA/ALA
ratio (17.5:1) but varied in the levels of dietary AA and DHA supplementation.
Diet LCP1 was structured to closely replicate the principal long chain
polyunsaturated fatty acids (PUFA) found in human breast milk and contained
0.9%
AA and 0.6% DHA (% of total fatty acids) whereas diet LCP3 contained
2.7% AA and
1.8% DHA. At the end of the study, animals were sacrificed and tissues
taken for
fatty acid analyses. We found no significant effects of diets on the
growth of
guinea pigs. Diets containing ALA had profoundly different effects
on tissue
fatty acid compositions compared with diets which contained the long
chain PUFA
(DHA and AA). In the retina and brain phospholipids, high-ALA diets
or dietary
DHA supplementation produced moderate relative increases in DHA levels.
There
was no change in retinal or brain AA proportions following dietary
AA
supplementation, even at the highest level. This was in contrast to
liver and
heart where tissue DHA proportions were low and AA predominated. In
these latter
tissues, dietary ALA had little effect on tissue DHA proportions although
the
proportion of AA was slightly depressed at the highest dietary ALA
intake, but
dietary DHA and AA supplements led to large increases (up to 10-fold)
in the
proportions of these PUFA. Tissue uptake of dietary AA and DHA appeared
maximal
for the LCP1 diet (replicate of breast milk) in the heart. There were
no
significant changes in the plasma levels of 11-dehydrothromboxane B2
(a
thromboxane A2 metabolite) for any diet. The data confirm that dietary
ALA is
less effective than dietary DHA supplementation (on a gram/gram basis)
in
increasing tissue DHA levels and that tissues vary greatly in their
response to
exogenous AA and DHA, with the levels of these long chain metabolites
being most
resistant to change in the retina and brain compared with liver and
heart.
Dietary DHA markedly increased tissue DHA proportions in both liver
and heart,
whereas the major effect of dietary AA was in the liver. Future studies
of the
effects of dietary DHA and AA supplementation should examine a variety
of
tissues rather than focusing only on neural tissue.
PMID: 10380119, UI: 99306787
34: Br J Cancer 1999 Jun;80(8):1231-5
Effect of a cachectic factor on carbohydrate metabolism and attenuation
by
eicosapentaenoic acid.
Hussey HJ, Tisdale MJ
Pharmaceutical Sciences Institute, Aston University, Birmingham, UK.
The effect of a proteolysis-inducing factor (PIF), produced by cachexia-inducing
tumours on glucose utilization by different tissues and the effect
of
pretreatment with the polyunsaturated fatty acid eicosapentaenoic acid
(EPA),
has been determined using the 2-deoxyglucose tracer technique. Mice
receiving
PIF showed a profound depression of body weight (2.3 g) over a 24-h
period,
which was completely abolished by pretreatment with a monoclonal antibody
to PIF
or by 3 days pretreatment with EPA at 500 mg kg(-1). Animals receiving
PIF
exhibited a marked hypoglycaemia, which was effectively reversed by
both
antibody and EPA pretreatment. There was an increase in glucose utilization
by
brain, heart and brown fat, but a decrease by kidney, white fat, diaphragm
and
gastrocnemius muscle after administration of PIF. Changes in organ
glucose
consumption were attenuated by either monoclonal antibody, EPA, or
both. There
was a decrease in 2-deoxyglucose uptake by C2C12 myoblasts in vitro,
which was
attenuated by EPA. This suggests a direct effect of PIF on glucose
uptake by
skeletal muscle. These results suggest that in addition to a direct
catabolic
effect on skeletal muscle PIF has a profound effect on glucose utilization
during cachexia.
PMID: 10376976, UI: 99303469
35: Brain Behav Evol 1999;53(4):173-9
Incorporation of dietary docosahexaenoic acid into the central nervous
system of
the yellowtail Seriola quinqueradiata.
Masuda R, Takeuchi T, Tsukamoto K, Sato H, Shimizu K, Imaizumi K
Ocean Research Institute, University of Tokyo, Nakano, Tokyo, Japan.
reiji@compuserve.com
In order to show the involvement of docosahexaenoic acid (DHA) in the
development of the central nervous system (CNS) in carangid fish, we
conducted
tracer experiments by feeding radioactive DHA to larval yellowtail
(Seriola
quinqueradiata). Artemia nauplii were enriched with 14C-labeled DHA
and fed to
larval yellowtail for eight or ten days. Autoradiography of frozen
sections,
using both electric imaging plates and X-ray sensitive film, clearly
showed that
DHA was incorporated into and retained in the brain, spinal cord, and
eyes. The
brain, eyes, gill raker, liver, guts, and other muscle and bone structures
were
dissected, and radioactivity was measured in each organ by liquid scintillation
counter. The results of this study suggest the incorporation of DHA
into the
brain. Considering our previous results indicating that DHA-free fish
cannot
form schools, we conclude that the incorporation of DHA into the brain
might be
a critical factor in the ontogeny of schooling behavior.
PMID: 10343083, UI: 99276368
36: J Lipid Res 1999 May;40(5):960-6
Developmental changes in rat brain membrane lipids and fatty acids.
The
preferential prenatal accumulation of docosahexaenoic acid.
Green P, Glozman S, Kamensky B, Yavin E
Department of Internal Medicine B, The Weizmann Institute of Science,
76100
Rehovot, Israel.
Information on the prenatal accumulation of rat brain membrane lipids
is scarce.
In this study we investigated in detail the fatty acid (FA) composition
of the
rat brain, on each day from embryonic day 12 (E12) up to birth, and
on 8 time
points during the first 16 days of postnatal life, and correlated the
FA changes
with well-described events of neurogenesis and synaptogenesis. Between
E14 and
E17, there was a steep increase in the concentration of all the FAs:
16:0
increased by 136%, 18:0 by 139%, 18:1 by 92%, 20:4n-6 by 98%, 22:4n-6
by 116%,
22:5n-6 by 220%, and 22:6n-3 by 98%. After this period and up to birth,
the
concentration of the FAs plateaued, except that of 22:6n-3, which accumulated
further, reaching an additional increase of 75%. After birth, except
22:5n-6,
all FAs steadily increased at various rates. Estimation of the FA/PL
molar
ratios showed that prenatally the ratios of all the FAs either decreased
or
remained constant, but that of 22:6n-3 increased more than 2-fold;
postnatally
the ratios remained constant, with the exception of 22:4n-6 and 22:5n-6,
which
decreased. In conclusion, prenatal accumulation of brain fatty acids
parallels
important events in neurogenesis. 22:6n-3 is exceptional inasmuch in
its steep
accumulation occurs just prior to synaptogenesis.
PMID: 10224166, UI: 99240809
37: J Nutr 1999 May;129(5):1079-89
Water maze performance is unaffected in artificially reared rats
fed diets
supplemented with arachidonic acid and docosahexaenoic acid.
Wainwright PE, Xing HC, Ward GR, Huang YS, Bobik E, Auestad N, Montalto M
Department of Health Studies and Gerontology, University of Waterloo,
Waterloo,
ON, N2L 3G1, Canada.
Four groups of male Long-Evans rats were reared artificially from postnatal
d 5
to 18 by being fed through a gastrostomy tube with rat milk substitutes
containing oils providing 10% linoleic acid and 1% alpha-linolenic
acid (g/100 g
fat); with the use of a 2 x 2 design, they were fed one of two levels
of
arachidonic acid (AA) and docosahexaenoic acid (DHA) (0.0 and 2.5 g/100
g of
fatty acids). A fifth artificially reared group was fed a diet high
in saturated
fat, and a sixth group was reared by dams fed a standard AIN-93M diet.
The pups
were weaned onto modified AIN-93G diets, with a fat composition similar
to that
fed during the artificial rearing period. Behavioral testing was conducted
between 6 and 9 wk of age; brain lipid composition was then assessed.
Relative
to the unsupplemented group (0.0 g/100 g AA and DHA), dietary supplementation
resulted in a wide range of AA (84-103%) and particularly DHA (86-119%)
levels
in forebrain membrane phospholipids. AA supplementation increased AA
levels and
decreased DHA levels, and DHA supplementation increased DHA levels
and decreased
AA levels, with the magnitude of these effects dependent on the level
of the
other fatty acid. DHA levels were very low in the saturated fat group.
The
groups did not differ on the place or cued version of the Morris water-maze,
but
on a test of working memory, the saturated fat group was impaired relative
to
the suckled control group. Further correlational analyses in the artificially
reared animals did not support a relationship between the wide range
of DHA and
AA levels in the forebrain and working-memory performance.
PMID: 10222403, UI: 99240836
38: Neurochem Res 1999 Mar;24(3):399-406
Dynamics of docosahexaenoic acid metabolism in the central nervous
system: lack
of effect of chronic lithium treatment.
Chang MC, Bell JM, Purdon AD, Chikhale EG, Grange E
Laboratory of Neurosciences, National Institute on Aging, National Institutes
of
Health, Bethesda, MD 20892, USA. mcjchang@box-m.nih.gov
Using a method and model developed in our laboratory to quantitatively
study
brain phospholipid metabolism, in vivo rates of incorporation and turnover
of
docosahexaenoic acid in brain phospholipids were measured in awake
rats. The
results suggest that docosahexaenoate incorporation and turnover in
brain
phospholipids are more rapid than previously assumed and that this
rapid
turnover dilutes tracer specific activity in brain docoshexaenoyl-CoA
pool due
to release and recycling of unlabeled fatty acid from phospholipid
metabolism.
Fractional turnover rates for docosahexaenoate within phosphatidylinositol,
choline glycerophospholipids, ethanolamine glycerophospholipids and
phosphatidylserine were 17.7, 3.1, 1.2, and 0.2 %.h(-1), respectively.
Chronic
lithium treatment, at a brain level considered to be therapeutic in
humans (0.6
micromol.g(-1)), had no effect on turnover of docosahexaenoic acid
in individual
brain phospholipids. Consistent with previous studies from our laboratory
that
chronic lithium decreased the turnover of arachidonic acid within brain
phospholipids by up to 80% and attenuated brain phospholipase A2 activity,
the
lack of effect of lithium on docosahexaenoate recycling and turnover
suggests
that a target for lithium's action is an arachidonic acid-selective
phospholipase A2.
PMID: 10215514, UI: 99140224
39: Lipids 1999 Jan;34(1):5-16
n-3 and n-6 fatty acid enrichment by dietary fish oil and phospholipid
sources
in brain cortical areas and nonneural tissues of formula-fed piglets.
Goustard-Langelier B, Guesnet P, Durand G, Antoine JM, Alessandri JM
Institut National de la Recherche Agronomique, Laboratoire de Nutrition
et
Securite Alimentaire, Jouy-en-Josas, France.
Sufficient availability of both n-3 and n-6 long-chain polyunsaturated
fatty
acids (LCPUFA) is required for optimal structural and functional development
in
infancy. The question has been raised as to whether infant formulae
would
benefit from enrichment with 20 and 22 carbon fatty acids.To address
this issue,
we determined the effect of fish oil and phospholipid (LCPUFA) sources
on the
fatty acid composition of brain cortical areas and nonneural tissues
of newborn
piglets fed artificially for 2 wk. They were fed sow milk, a control
formula, or
the formula enriched with n-3 fatty acids from a low-20:5n-3 fish oil
added at a
high or a low concentration, or the formula enriched with n-3 and n-6
fatty
acids from either egg yolk- or pig brain-phospholipids. Both the fish
oil- and
the phospholipid-enriched formula produced significantly higher plasma
phospholipid 22:6n-3 concentrations than did the control formula. The
22:6n-3
levels in the brain, hepatic, and intestinal phospholipids were significantly
correlated with plasma values, whereas cardiac 22:6n-3 content appeared
to
follow a saturable dose-response. Feeding sow milk resulted in a much
higher
20:4n-6 content in nonneural tissues than did feeding formula. Supplementation
with egg phospholipid increased the 20:4n-6 content in the heart, red
blood
cells, plasma, and intestine in comparison to the control formula,
while pig
brain phospholipids exerted this effect in the heart only. The addition
of 4.5%
fish oil in the formula was associated with a decline in 20:4n-6 in
the cortex,
cerebellum, heart, liver, and plasma phospholipids, whereas using this
source at
1.5% limited the decline to the cerebellum, liver, and plasma. Whatever
the
dietary treatment, the phosphatidylethanolamine 20:4n-6 level was 10-20%
higher
in the brain temporal lobe than in the parietal, frontal, and occipital
lobes in
the temporal lobe by administering the formula enriched with egg or
brain
phospholipids. In conclusion, feeding egg phospholipids to neonatal
pigs
increased both the 22:6n-3 content in the brain and the 20:4n-6 content
in the
temporal lobe cortex. This source also increased the 22:6n-3 levels
in nonneural
tissues with only minor alterations of 20:4n-6. These data support
the notion
that infant formulae should be supplemented with both 22:6n-3 and 20:4n-6
rather
than with 22:6n-3 alone.
PMID: 10188591, UI: 99202474
40: Lipids 1999 Feb;34(2):139-49
Neonatal polyunsaturated fatty acid metabolism.
Innis SM, Sprecher H, Hachey D, Edmond J, Anderson RE
Department of Paediatrics, University of British Columbia, Vancouver,
Canada.
sinnis@unixg.ubc.ca
The importance of n-6 and n-3 polyunsaturated fatty acids (PUFA) in
neonatal
development, particularly with respect to the developing brain and
retina, is
well known. This review combines recent information from basic science
and
clinical studies to highlight recent advances in knowledge on PUFA
metabolism
and areas where research is still needed on infant n-6 and n-3 fatty
acid
requirements. Animal, cell culture, and infant studies are consistent
in
demonstrating that synthesis of 22:6n-3 involves C24 PUFA and that
the amounts
of 18:2n-6 and 18:3n-3 influence PUFA metabolism. Studies to show that
addition
of n-6 fatty acids beyond delta6-desaturase alters n-6 fatty acid metabolism
with no marked increase in tissue 20:4n-6 illustrate the limitations
of analyses
of tissue fatty acid compositions as an approach to study the effects
of diet on
fatty acid metabolism. New information to show highly selective pathways
for n-6
and n-3 fatty acid uptake in brain, and efficient pathways for conservation
of
22:6n-3 in retina emphasizes the differences in PUFA metabolism among
different
tissues and the unique features which allow the brain and retina to
accumulate
and maintain high concentrations of n-3 fatty acids. Further elucidation
of the
delta6-desaturases involved in 24:5n-6 and 22:6n-3 synthesis; the regulation
of
fatty acid movement between the endoplasmic reticulum and peroxisomes;
partitioning to acylation, desaturation and oxidation; and the effects
of
dietary and hormonal factors on these pathways is needed for greater
understanding of neonatal PUFA metabolism.
Publication Types:
Review
Review, tutorial
PMID: 10102240, UI: 99200363
41: Lipids 1999 Feb;34(2):115-24
Dietary menhaden, seal, and corn oils differentially affect lipid
and ex vivo
eicosanoid and thiobarbituric acid-reactive substances generation
in the guinea
pig.
Murphy MG, Wright V, Scott J, Timmins A, Ackman RG
Department of Physiology and Biophysics, Dalhousie University, Halifax,
Nova
Scotia, Canada. mary.murphy@dal.ca
This investigation was carried out to characterize the effects of specific
dietary marine oils on tissue and plasma fatty acids and their capacity
to
generate metabolites (prostanoids, lipid peroxides). Young male guinea
pigs were
fed nonpurified diet (NP), or NP supplemented (10%, w/w) with menhaden
fish oil
(MO), harp seal oil (SLO), or corn oil (CO, control diet) for 23 to
28 d. Only
the plasma showed significant n-3 polyunsaturated fatty acid (PUFA)-induced
reductions in triacylglycerol (TAG) or total cholesterol concentration.
Proportions of total n-3 PUFA in organs and plasma were elevated significantly
in both MO and SLO dietary groups (relative to CO), and in all TAG
fractions
levels were significantly higher in MO- than SLO-fed animals. The two
marine oil
groups differed in their patterns of incorporation of eicosapentaenoic
acid
(EPA). In guinea pigs fed MO, the highest levels of EPA were in the
plasma TAG,
whereas in SLO-fed animals, maximal incorporation of EPA was in the
heart polar
lipids (PL). In both marine oil groups, the greatest increases in both
docosahexaenoic acid (22:6n-3, DHA) and docosapentaenoic acid (22:5n-3,
DPA),
relative to the CO group, were in plasma TAG, although the highest
proportions
of DHA and DPA were in liver PL and heart TAG, respectively. In comparing
the MO
and SLO groups, the greatest difference in levels of DHA was in heart
TAG (MO >
SLO, P < 0.005), and in levels of DPA was in heart PL (SLO > MO,
P < 0.0001).
The only significant reduction in proportions of the major n-6 PUFA,
arachidonic
acid (AA), was in the heart PL of the SLO group (SLO > MO = CO, P <
0.005).
Marine oil feeding altered ex vivo generation of several prostanoid
metabolites
of AA, significantly decreasing thromboxane A2 synthesis in homogenates
of
hearts and livers of guinea pigs fed MO and SLO, respectively (P <
0.04 for
both, relative to CO). Lipid peroxides were elevated to similar levels
in MO-
and SLO-fed animals in plasma, liver, and adipose tissue, but not in
heart
preparations. This study has shown that guinea pigs respond to dietary
marine
oils with increased organ and plasma n-3 PUFA, and changes in potential
synthesis of metabolites. They also appear to respond to n-3 PUFA-enriched
diets
in a manner that is different from that of rats.
PMID: 10102237, UI: 99200360
42: Audiology 1999 Jan-Feb;38(1):13-8
Changes in auditory brainstem responses in alpha-linolenic acid deficiency
as a
function of age in rats.
Bourre JM, Durand G, Erre JP, Aran JM
INSERM U 26, Hopital Fernand, Vidal, Paris, France.
Auditory brainstem responses (ABRs) to click stimuli have been compared
in young
(21-day-old), adult (6-month-old), and old (18-month-old) rats fed
a normal
(Arachid-Colza) or an alpha-linolenic acid deficient (Arachid only)
diet. Wave I
amplitude and latency did not show any significant change with either
age or
diet. However, wave III showed a progressive decrease in amplitude
and latency
from young to adult and from adult to old rats having a normal diet.
With
alpha-linolenic acid deficiency, wave III amplitude and latency values
decreased
faster than in the normal diet control groups. Although final values
in the old
groups with the two diets were similar, with alpha-linolenic acid deficiency
values for wave III decreased to this final level in the adult group.
These data
indicate that the central auditory nervous system ages faster, or earlier,
with
a fatty acid deficiency.
PMID: 10052831, UI: 99160196
43: J Neurochem 1999 Mar;72(3):1133-8
Antioxidative effects of docosahexaenoic acid in the cerebrum versus
cerebellum
and brainstem of aged hypercholesterolemic rats.
Hossain MS, Hashimoto M, Gamoh S, Masumura S
Department of Physiology, Shimane Medical University, Izumo, Japan.
Female Wistar rats (100 weeks old) were divided into two groups; one
group was
fed a high-cholesterol diet (HC) and the other a high-cholesterol diet
plus
docosahexaenoic acid (HC-fed DHA rats). Fatty acid concentrations in
brain
tissues were analyzed by gas chromatography. In the HC-fed DHA rats,
brain
catalase (CAT), GSH, and glutathione peroxidase (GPx) increased in
the cerebrum
but not in the brainstem or cerebellum. The rate of increase was 23.0%
for CAT,
24.5% for GSH, and 26.3% for GPx compared with that in the HC animals
(p <
0.05). In the cerebrum of the HC-fed DHA rats, CAT and GPx increased,
with an
increase in the ratio of DHA to arachidonic acid. The cerebrum, unlike
the other
areas of the brain, seems to be more sensitive to DHA in stimulating
CAT and
GPx. We suggest that DHA plays an important role in inducing an antioxidative
defense against active oxygen by enhancing the cerebral activities
of CAT, GPx,
and GSH.
PMID: 10037485, UI: 99155089
44: J Nutr 1999 Feb;129(2):431-7
High-linoleate and high-alpha-linolenate diets affect learning ability
and
natural behavior in SAMR1 mice.
Umezawa M, Kogishi K, Tojo H, Yoshimura S, Seriu N, Ohta A, Takeda T, Hosokawa M
Department of Nutrition, Koshien University, 10-1 Momijigaoka, Takarazuka,
Hyogo
665-0006, Japan.
Semipurified diets incorporating either perilla oil [high in alpha-linolenate,
18:3(n-3)] or safflower oil [high in linoleate, 18:2(n-6)] were fed
to
senescence-resistant SAMR1 mouse dams and their pups. Male offspring
at 15 mo
were examined using behavioral tests. In the open field test, locomotor
activity
during a 5-min period was significantly higher in the safflower oil
group than
in the perilla oil group. Observations of the circadian rhythm (48
h) of
spontaneous motor activity indicated that the safflower oil group was
more
active than the perilla oil group during the first and second dark
periods. The
total number of responses to positive and negative stimuli was higher
in the
safflower oil group than in the perilla oil group in the light and
dark
discrimination learning test, but the correct response ratio was lower
in the
safflower oil group. The difference in the (n-6)/(n-3) ratios of the
diets
reflected the proportions of (n-6) polyunsaturated fatty acids, rather
than
those of (n-3) polyunsaturated fatty acids in the brain total fatty
acids, and
in the proportions of (n-6) and (n-3) polyunsaturated fatty acids in
the total
polyunsaturated fatty acids of the brain phospholipids. These results
suggest
that in SAMR1 mice, the dietary alpha-linolenate/linoleate balance
affects the
(n-6)/(n-3) ratio of brain phospholipids, and this may modify emotional
reactivity and learning ability.
PMID: 10024623, UI: 99150510
45: J Neurochem 1999 Feb;72(2):734-40
F4-isoprostanes as specific marker of docosahexaenoic acid peroxidation
in
Alzheimer's disease.
Nourooz-Zadeh J, Liu EH, Yhlen B, Anggard EE, Halliwell B
Centre for Clinical Pharmacology and Therapeutic Toxicology, Department
of
Medicine, University College, London, England.
F2-isoprostanes are prostaglandin-like compounds derived from free
radical-catalysed peroxidation of arachidonic acid. Peroxidation of
eicosapentaenoic acid produces F3-isoprostanes, whereas peroxidation
of
docosahexaenoic acid would give F4-isoprostanes. This study demonstrates
the
presence of esterified F4-isoprostanes in human brain and shows that
levels are
elevated in certain brain cortex regions in Alzheimer's disease. Our
data with
Alzheimer's disease suggest that analysis of F4-isoprostanes will provide
new
opportunities to study lipid peroxidation in the neurodegenerative
diseases.
PMID: 9930747, UI: 99127937
46: Pediatr Res 1999 Jan;45(1):87-93
Bioequivalence of dietary alpha-linolenic and docosahexaenoic acids
as sources
of docosahexaenoate accretion in brain and associated organs of
neonatal
baboons.
Su HM, Bernardo L, Mirmiran M, Ma XH, Corso TN, Nathanielsz PW, Brenna JT
Division of Nutritional Sciences, Cornell University, Ithaca, New York
14853,
USA.
The dietary bioequivalence of alpha-linolenic (LNA) and docosahexaenoic
acids
(DHA) as substrates for brain and retinal n-3 fatty acid accretion
during the
brain growth spurt is reported for neonatal baboons who consumed a
long-chain-polyunsaturate free commercial human infant formula with
a n-6/n-3
ratio of 10:1. Neonates received oral doses of 13C-labeled fatty acids
(LNA*) or
(DHA*) at 4 wk of age, and at 6 wk brain (occipital cortex), retina,
retinal
pigment epithelium, liver, erythrocytes, and plasma were analyzed.
In the brain,
1.71% of the preformed DHA* dose was detected, whereas 0.23% of the
LNA* dose
was detected as DHA*, indicating that preformed DHA is 7-fold more
effective
than LNA-derived DHA as a source for DHA accretion. In LNA*-dosed animals,
DHA*
was greater than 60% of labeled fatty acids in all tissues except erythrocytes,
where docosapentaenoic acid was 55%. Estimates using dietary LNA levels
as
tracees indicate that brain turnover of DHA is less than 5% per week
between
weeks 4 and 6 of life. For retina and retinal pigment epithelium, preformed
DHA
was at levels 12-fold and 15-fold greater than LNA-derived DHA. Liver,
plasma,
and erythrocytes ratios were 27, 29, and 51, respectively, showing
that these
pools do not parallel tissue metabolism of a single dose of omega-3
fatty acids.
The distributions of labeled fatty acids for LNA*-dosed animals were
similar, in
the order DHA > DPA > EPA > LNA, except for erythrocytes where docosapentaenoic
acid predominated. These are the first direct measurements of the bioequivalence
of DHA and LNA in neonatal primate brain and associated tissues.
PMID: 9890614, UI: 99105620
47: J Neurochem 1999 Jan;72(1):338-45
Preferential transfer of 2-docosahexaenoyl-1-lysophosphatidylcholine
through an
in vitro blood-brain barrier over unesterified docosahexaenoic acid.
Bernoud N, Fenart L, Moliere P, Dehouck MP, Lagarde M, Cecchelli R, Lecerf J
U 352 INSERM, Biochimie et Pharmacologie, INSA-Lyon, Villeurbanne, France.
The passage of either unesterified docosahexaenoic acid (DHA) or
lysophosphatidylcholine-containing DHA (lysoPC-DHA) through an in vitro
model of
the blood-brain barrier was investigated. The model was constituted
by a brain
capillary endothelial cell monolayer set over the medium of an astrocyte
culture. Cells were incubated for 4 h with a medium devoid of serum,
then the
endothelial cell medium was replaced by the same medium containing
labeled DHA
or lysoPC-DHA and incubations were performed for 2 h. DHA uptake by
cells and
its transfer to the lower medium (astrocyte medium when they were present)
were
measured. When the lower medium from preincubation and astrocytes were
maintained during incubation, the passage of lysoPC-DHA was higher
than that of
unesterified DHA. The passage of both forms decreased when astrocytes
were
removed. The preference for lysoPC-DHA was not seen when the lower
medium from
preincubation was replaced by fresh medium, and was reversed when albumin
was
added to the lower medium. A preferential lysoPC-DHA passage also occurred
after
2 h with brain endothelial cells cultured without astrocytes but not
with aortic
endothelial cells cultured and incubated under the same conditions.
Altogether,
these results suggest that the blood-brain barrier cells released components
favoring the DHA transfer and exhibit a preference for lysoPC-DHA.
PMID: 9886086, UI: 99101177
48: J Biol Chem 1999 Jan 1;274(1):471-7
Cloning, expression, and nutritional regulation of the mammalian
Delta-6
desaturase.
Cho HP, Nakamura MT, Clarke SD
Program of Nutritional Sciences and the Institute for Cellular and Molecular
Biology, The University of Texas-Austin, Austin, Texas 78712, USA.
Arachidonic acid (20:4(n-6)) and docosahexaenoic acid (22:6(n-3)) have
a variety
of physiological functions that include being the major component of
membrane
phospholipid in brain and retina, substrates for eicosanoid production,
and
regulators of nuclear transcription factors. The rate-limiting step
in the
production of 20:4(n-6) and 22:6(n-3) is the desaturation of 18:2(n-6)
and
18:3(n-3) by Delta-6 desaturase. In this report, we describe the cloning,
characterization, and expression of a mammalian Delta-6 desaturase.
The open
reading frames for mouse and human Delta-6 desaturase each encode a
444-amino
acid peptide, and the two peptides share an 87% amino acid homology.
The amino
acid sequence predicts that the peptide contains two membrane-spanning
domains
as well as a cytochrome b5-like domain that is characteristic of nonmammalian
Delta-6 desaturases. Expression of the open reading frame in rat hepatocytes
and
Chinese hamster ovary cells instilled in these cells the ability to
convert
18:2(n-6) and 18:3(n-3) to their respective products, 18:3(n-6) and
18:4(n-3).
When mice were fed a diet containing 10% fat, hepatic enzymatic activity
and
mRNA abundance for hepatic Delta-6 desaturase in mice fed corn oil
were 70 and
50% lower than in mice fed triolein. Finally, Northern analysis revealed
that
the brain contained an amount of Delta-6 desaturase mRNA that was several
times
greater than that found in other tissues including the liver, lung,
heart, and
skeletal muscle. The RNA abundance data indicate that prior conclusions
regarding the low level of Delta-6 desaturase expression in nonhepatic
tissues
may need to be reevaluated.
PMID: 9867867, UI: 99085046