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The effect of feeding diets with different n-6/n-3 fatty
acids ratios on adipose tissue of deposition in the rat.
Sherrington EJ, Jeffery NM, Calder PC.
Department of Biochemistry, University of Oxford, UK.
PMID: 8736818 [PubMed - indexed for MEDLINE]
Dietary supplementation of very long-chain n-3 fatty
acids decreases whole body lipid utilization in the rat.
Rustan AC, Hustvedt BE, Drevon CA.
Department of Pharmacology, University of Oslo, Norway.
Rats were fed lard or n-3 fatty acid-supplemented diets ad libitum to study
whole body oxidation of lipid and carbohydrate. One group of male rats was fed
21% fat (by weight) containing 19.5% lard and sufficient amounts of essential
fatty acids (1.5%). Another group of rats had 6.5% of the lard replaced by
ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
The rats were fed these diets for 6-8 weeks. Body weight gain was similar for
the two groups and absorption of fat was complete in animals fed both types of
fatty acids. Indirect calorimetric measurements, after 3-5 weeks on these
diets, by continuous registration of O2 consumption and CO2 formation showed
no difference in mean energy expenditure during the experimental period.
However, the mean respiratory quotient (RQ) was significantly increased for
animals fed the n-3 fatty acid-supplemented diet. This was noted both under
fasting conditions and after receiving a test meal of similar fatty acid
composition for both feeding groups. Thus, mean substrate utilization
demonstrated reduced oxidation of fat and increased oxidation of carbohydrate,
during fasting as well as fed periods for the n-3 fatty acid group as compared
to the lard group. After an additional 2-3 weeks, blood plasma, liver, and
muscle samples were collected, and adipocytes and hepatocytes were isolated.
Reduced postprandial plasma concentrations of triacylglycerol, phospholipids,
unesterified fatty acids, and glycerol were promoted by the n-3 fatty acid
diet as compared to lard. Plasma concentration of glucose was slightly
increased, and liver and muscle content of glycogen were decreased in the n-3
fatty acid-fed rats. Experiments with isolated adipocytes showed decreased
basal lipolysis after feeding n-3 fatty acids for 6-8 weeks for suspended
epididymal adipocytes, whereas stimulated lipolysis by isoproterenol (0.1
microM) was higher in both epididymal and mesenteric adipocytes from rats fed
n-3 fatty acids as compared to animals fed lard. In addition, epididymal
adipocytes from rats fed n-3 fatty acids were significantly smaller than cells
from animals fed lard. Hepatic peroxisomal fatty acid oxidation was
significantly higher for n-3 fatty acid-supplemented animals, but total fatty
acid oxidation was similar in both dietary groups. The hepatic content of
triacylglycerol and phospholipids was similar for both diets. These results
demonstrate that n-3 fatty acid replacement of a high-fat diet containing
mostly saturates and monoenes for several weeks promotes reduced use of fat as
energy source. This may be explained by decreased plasma concentration of
unesterified fatty acids.(ABSTRACT TRUNCATED AT 400 WORDS)
PMID: 8409764 [PubMed - indexed for MEDLINE]
-
Postprandial decrease in plasma unesterified fatty
acids during n-3 fatty acid feeding is not caused by accumulation of fatty
acids in adipose tissue.
Rustan AC, Hustvedt BE, Drevon CA.
Department of Pharmacology, School of Pharmacy, University of Oslo, P.O.
Box 1068, Blindern, N-0316 Oslo, Norway. arild.rustan@farmasi.uio.no
Dietary supplementation of very long-chain n-3 fatty acids to rats reduces
postprandial plasma concentrations of triacylglycerol, unesterified fatty
acids and glycerol after long-term feeding by unknown mechanisms [Rustan
et al., J. Lipid Res. 34 (1993) 1299-1309]. In the present study we
examine the role of adipose tissues in metabolism of fatty acids.
Postprandial plasma concentrations of triacylglycerol, unesterified fatty
acids and glycerol were reduced by 75%, 50% and 30%, respectively, during
49 days of feeding high-fat diets containing n-3 fatty acids (6.5% n-3
fatty acid concentrate, 13% lard) as compared to lard (19.5% lard). These
differences were observed already after two days of feeding. Plasma
concentration of unesterified very long-chain n-3 fatty acids increased to
50 microM in n-3 fatty acid-supplemented rats, whereas these fatty acids
were undetectable in lard-fed animals. The n-3 fatty acid-enriched diet
limited cell volumes of perirenal and epididymal adipocytes by 40% and
30%, respectively, after 49 days, as compared to lard feeding. This
reduction in cell volume was not due to reduced synthesis of glycerolipids
in epididymal adipocytes. Acute incubation of perirenal and epididymal
adipocytes with oleic acid or eicosapentaenoic acid, caused similar
increase in synthesis of triacylglycerol. Dietary supplementation with n-3
fatty acids decreased basal and total lipolysis (isoprenalin-stimulated)
in perirenal adipocytes. Basal lipolysis in epididymal adipocytes was
reduced by n-3 fatty acids only after 49 days. n-3 fatty acids increased
total lipolysis in mesenteric and subcutaneous fat cells compared to
adipocytes derived from lard-fed animals, whereas basal lipolysis was
unchanged. These results suggest that the reduced postprandial plasma
concentration of unesterified fatty acids after n-3 fatty
acid-supplementation is not caused by accumulation of fatty acids in
adipose tissue. The reduced trophic growth of adipocytes might be due to
decreased supply of unesterified fatty acids for triacylglycerol storage.
(c) 1998 Elsevier Science B.V.
PMID: 9487146 [PubMed - indexed for MEDLINE]
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Developmental sensitivity of the brain to dietary n-3
fatty acids.
Anderson GJ.
Section of Clinical Nutrition and Lipid Metabolism, Oregon Health Sciences
University, Portland 97201.
The developing brain readily incorporates dietary fatty acids, while the
adult brain is refractory to changes in fatty acid composition. In order
to localize the time in development when this transition occurs, chicks
were fed large amounts of n-3 fatty acids from fish oil beginning at 0, 1,
2, or 3 weeks of age. Control chicks were fed a soybean oil-based diet, as
were the experimental chicks before introduction of the fish oil diet.
Resistance to diet-induced increases in brain n-3 fatty acid levels began
at 2 weeks of age, and was substantial at 3 weeks. Docosahexaenoic acid
was particularly resistant to change as the brain matured, increasing by
38% when fish oil was fed from time of hatching, but only by 8% when fish
oil feeding was delayed until 3 weeks of age. Dietary fish oil caused a
compensatory decrease in brain n-6 fatty acids, and this decrease occurred
even at later time points when the rise in brain n-3 fatty acids was much
less prominent. The liver incorporated high levels of n-3 fatty acids at
all ages, and compensated by decreasing monounsaturated fatty acids at
early time points and n-6 fatty acids at later time points. These results
show that resistance to changes in brain fatty acid composition is evident
at a relatively early age, before brain development is complete.
PMID: 8138711 [PubMed - indexed for MEDLINE]
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Incorporation of dietary n-3 fatty acids into the fatty
acids of human adipose tissue and plasma lipid classes.
Leaf DA, Connor WE, Barstad L, Sexton G.
Department of Medicine, West Los Angeles Veterans Administration Medical
Center, CA 90073, USA.
The consumption of n-3 fatty acids from seafood has been related to a
lower incidence of coronary artery disease. Adipose tissue composition has
served as a biological marker of chronic ingestion of many dietary
polyunsaturated fatty acids. However, the incorporation of n-3 fatty acids
into the fat depots has not been studied in humans. Daily dietary
supplementation with > or = 10 g n-3 fatty acids from fish oil for >
12 mo resulted in significantly greater 20:5n-3, 22:5n-3, and 22:6n-3
concentrations in fatty acids of adipose tissue, and a greater 20: 5n-3
fatty acid content in plasma lipid classes (cholesterol esters,
phospholipids, and free fatty acids) of supplemented subjects compared
with nonsupplemented control subjects. Combined values for all subjects
indicated that fatty acid concentrations of n-3 plasma lipid classes,
including 20:5n-3, 22:5n-3, 22:6n-3, and total n-3, significantly
correlated with corresponding concentrations of fatty acids in adipose
tissue. These findings indicate that the long-term ingestion of large
amounts of n-3 fatty acids in humans resulted in their incorporation into
the adipose tissue fatty acids. Incorporation of the fatty acids into
adipose tissue warrants consideration for use in clinical studies
requiring precise documentation of long-term n-3 fatty acid consumption.
Publication Types:
- Clinical Trial
- Controlled Clinical Trial
PMID: 7598068 [PubMed - indexed for MEDLINE]
-
Comment in:
Very-long-chain n-3 fatty acids as biomarkers for
intake of fish and n-3 fatty acid concentrates.
Andersen LF, Solvoll K, Drevon CA.
Institute for Nutrition Research, University of Oslo, Norway.
We examined how supplementation with very-long-chain n-3 fatty acids was
reflected in the concentration of these fatty acids in plasma
phospholipids of 363 Norwegian men and women. The concentration of
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in plasma
phospholipids was significantly higher among individuals supplemented with
n-3 fatty acids after the supplementation period than before. We also
examined the relation between dietary intake of fatty acids measured with
a 180-item quantitative food-frequency questionnaire and the concentration
of the same fatty acids in plasma phospholipids in 579 men and women.
Correlation coefficients between plasma phospholipid fatty acids and
dietary intake of fatty acids were 0.51 and 0.49 for EPA and DHA,
respectively. The correlation between fish intake and n-3 fatty acids in
plasma phospholipids was 0.37. These results suggest that dietary intake
measured with our food-frequency questionnaire may be used to predict the
biological availability of some of the essential n-3 fatty acids.
PMID: 8780338 [PubMed - indexed for MEDLINE]
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The influence of dietary n-3 fatty acids on plasma
lipids and lipoproteins.
Illingworth DR, Schmidt EB.
Department of Medicine, Oregon Health Sciences University, Portland
97201-3098.
The body of epidemiologic data indicates that the incidence of
cardiovascular disease is lower in populations whose habitual diet is rich
in fish. It is unclear however to what extent this apparent protection is
due to the intake of n-3 fatty acids in sea food or to the fact that these
subjects have generally been consuming lower amounts of saturated fatty
acids in their diets. It is clear, however, that when the dietary intake
of n-3 fatty acids is increased to 4-8 g/day distinct metabolic effects
are observed, including reductions in plasma triglycerides, effects on
platelet function and coagulation factors and blood pressure. Larger
intakes exert a more profound hypotriglyceridemic effect, and in patients
with primary hypercholesterolemia daily intakes exceeding 10-12 g/day are
effective in reducing plasma concentrations of LDL cholesterol. However,
from a practical point of view, the lipid-modifying effects of
supplemental dietary n-3 fatty acids are most clearly observed in patients
with hypertriglyceridemia and the major usefulness of dietary n-3 fatty
acids is in the treatment of this patient population, particularly
patients with severe hypertriglyceridemia or potentially those with Type
III hyperlipoproteinemia. Further studies are needed to better define the
potential utility of dietary n-3 fatty acids when used in combination with
lipid-lowering drugs to reduce lipoprotein concentrations in patients with
combined hyperlipoproteinemia or severe hypertriglyceridemia.
Publication Types:
PMID: 8489156 [PubMed - indexed for MEDLINE]
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Human requirement for N-3 polyunsaturated fatty acids.
Simopoulos AP.
The Center for Genetics Nutrition and Health, Washington, DC 20009, USA.
cgnh@bellatlantic.net
The diet of our ancestors was less dense in calories, being higher in
fiber, rich in fruits, vegetables, lean meat, and fish. As a result, the
diet was lower in total fat and saturated fat, but contained equal amounts
of n-6 and n-3 essential fatty acids. Linoleic acid (LA) is the major n-6
fatty acid, and alpha-linolenic acid (ALA) is the major n-3 fatty acid. In
the body, LA is metabolized to arachidonic acid (AA), and ALA is
metabolized to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
The ratio of n-6 to n-3 essential fatty acids was 1 to 2:1 with higher
levels of the longer-chain polyunsaturated fatty acids (PUFA), such as
EPA, DHA, and AA, than today's diet. Today this ratio is about 10 to 1:20
to 25 to 1, indicating that Western diets are deficient in n-3 fatty acids
compared with the diet on which humans evolved and their genetic patterns
were established. The n-3 and n-6 EPA are not interconvertible in the
human body and are important components of practically all cell membranes.
The N-6 and n-3 fatty acids influence eicosanoid metabolism, gene
expression, and intercellular cell-to-cell communication. The PUFA
composition of cell membranes is, to a great extent, dependent on dietary
intake. Therefore, appropriate amounts of dietary n-6 and n-3 fatty acids
need to be considered in making dietary recommendations. These two classes
of PUFA should be distinguished because they are metabolically and
functionally distinct and have opposing physiological functions; their
balance is important for homeostasis and normal development. Studies with
nonhuman primates and human newborns indicate that DHA is essential for
the normal functional development of the retina and brain, particularly in
premature infants. A balanced n-6/n-3 ratio in the diet is essential for
normal growth and development and should lead to decreases in
cardiovascular disease and other chronic diseases and improve mental
health. Although a recommended dietary allowance for essential fatty acids
does not exist, an adequate intake (AI) has been estimated for n-6 and n-3
essential fatty acids by an international scientific working group. For
Western societies, it will be necessary to decrease the intake of n-6
fatty acids and increase the intake of n-3 fatty acids. The food industry
is already taking steps to return n-3 essential fatty acids to the food
supply by enriching various foods with n-3 fatty acids. To obtain the
recommended AI, it will be necessary to consider the issues involved in
enriching the food supply with n-3 PUFA in terms of dosage, safety, and
sources of n-3 fatty acids.
Publication Types:
PMID: 10901194 [PubMed - indexed for MEDLINE]
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Fish oil n-3 fatty acids selectively limit the
hypertrophy of abdominal fat depots in growing rats fed high-fat diets.
Belzung F, Raclot T, Groscolas R.
Centre d'Ecologie et Physiologie Energetiques, Centre National de la
Recherche Scientifique, Strasbourg, France.
Because dietary n-3 polyunsaturated fatty acids (n-3 PUFA) from fish oils
have profound effects on lipid metabolism, we examined whether they
influence the growth of adipose tissue at different locations in growing
rats. Rats were fed for 4 wk on high-fat (HF) diets (20% fat) containing
very low (L), medium (M), and high (H) amounts of n-3 PUFA but similar
amounts of saturated fatty acids and n-6 PUFA. A fourth group was fed a
standard laboratory diet (control group) to estimate changes in adipose
tissue mass related to growth. At the end of the dietary treatment, the
lipid mass (LM) of the four major adipose depots (subcutaneous, SC;
mesenteric, MES; retroperitoneal, RP; epididymal, EPI) and total adiposity
were significantly higher in each of the three HF groups than in the
control group. The lipid gain in EPI was due to fat cell hypertrophy
alone, whereas RP showed both hypertrophy and hyperplasia. Energy intake,
fatty acid excretion, and body mass were the same in the three groups fed
HF diets. Similarly, there was no difference in the LM or in lipid gains
specifically caused by HF feeding of SC and MES between the HF groups. In
contrast, the LM of RP was significantly lower in the H than in the L and
M groups (50 and 30%, respectively). The LM of EPI was also 30% lower in
the H than in the L group.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 8322963 [PubMed - indexed for MEDLINE]
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Influence of exogenous application of n-3 fatty acids
on meat quality, lipid composition, and oxidative stability in pigs.
Nurnberg K, Kuchenmeister U, Nurnberg G, Ender K, Hackl W.
Research Institute for the Biology of Farm Animals, Division of Muscle
Biology and Growth, Dummerstorf, Germany.
The effect of dietary n-3 fatty acids on the fatty acid composition and
lipid peroxidation of different tissues in pigs were studied. 20 castrated
male pigs were included in this investigation, one half was fed daily a
diet containing 1.3 g n-3 fatty acids/kg diet (control) and 10 pigs were
fed a diet containing 14 g n-3 fatty acids/kg diet (n-3 diet) at the
growing-finishing period. The intake of dietary n-3 fatty acids increased
the concentration of these fatty acids in backfat, and the neutral and
polar fractions of skeletal muscle and heart homogenates. The polar
fraction showed an increased relative concentration of n-3 fatty acids in
comparison to control, while the n-6 fatty acid content was reduced. In
heart homogenates there was an enlargement of n-3 fatty acids both in
polar lipids and in neutral lipids whilst n-6 fatty acids were decreased.
Feeding n-3 fatty acid enriched diet had no influence on meat quality
parameters drip loss, meat colour or pH value. The lipid peroxidation
(measured as malondialdehyde equivalents) was in the order liver >
heart > skeletal muscle with higher values in the n-3 group. However,
by stimulation of oxidation by Fe2+/ascorbate for 3 hours the order of
oxidative products in the n-3 group was muscle > liver > heart,
whereas in the control group the order was liver > heart = muscle.
Summarized, feeding a highly n-3 fatty acid enriched diet caused an
incorporation of these fatty acids and increased the susceptibility to
peroxidation in all investigated tissues.
PMID: 10548976 [PubMed - indexed for MEDLINE]
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Effect of various n-3/n-6 fatty acid ratio contents of
high fat diets on rat liver and heart peroxisomal and mitochondrial
beta-oxidation.
Vamecq J, Vallee L, de la Porte PL, Fontaine M, de Craemer D, van den
Branden C, Lafont H, Grataroli R, Nalbone G.
North France Center for the Study of Childhood Epilepsy, Department of
Paediatric Neurology, Hopital B, Centre Hospitalier Universitaire de Lille.
The present work extends tissue investigations previously performed in rat
gastric mucosa on lipid metabolism alterations caused by n-3 and n-6 fatty
acid-enriched diets. Liver and heart tissues are here studied and
demonstrated to undergo, upon exposure to high fat diets with various
n-3/n-6 fatty acid ratio contents, biochemical and morphological changes
which may be enumerated as follows: (1) Rat liver peroxisomal
prostaglandin E2, fatty acid but not bile acid beta-oxidation rates are
enhanced, especially upon the diet with the higher n-3/n-6 fatty acid
ratio. Mitochondrial beta-oxidation rates are little or not affected by
the high fat diets. (2) Rat liver carnitine acyltransferases are
stimulated by the high fat diets, the more rich the n-3 fatty acid
content, the more pronounced the stimulatory effect. (3) Rat heart
peroxisomal and mitochondrial beta-oxidation rates were increased in
animals receiving the n-3 fatty acid-enriched diet. At a low n-3/n-6 fatty
acid ratio content of the diet, these oxidizing rate values were in
control range. The carnitine acyltransferase activities were increased in
rat heart to different extents, depending on the n-3/n-6 fatty acid ratio
content of the diet. (4) Ultrastructural examination and morphometric
determinations on hepatocytes from rats receiving the diets with the
lowest and the highest n-3/n-6 fatty acid ratio contents disclose that in
the latter case the numbers and fractional volumes of peroxisomes and
mitochondria are significantly higher than in the former case.
PMID: 8399339 [PubMed - indexed for MEDLINE]
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Changes in platelet aggregation and lipid metabolism in
rats given dietary lipids containing different n-3 polyunsaturated fatty
acids.
Yamada N, Shimizu J, Wada M, Takita T, Innami S.
Department of Nutrition, Faculty of Agriculture, Tokyo University of
Agriculture, Japan.
We compared the effects of different n-3 polyunsaturated fatty acids (PUFA)
on platelet aggregation and lipid metabolism in rats. alpha-Linolenic acid
(ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were used
as n-3 PUFA sources. The rats were fed diets containing 10% lipids
(polyunsaturated/saturated fatty acid (P/S) ratio = 1.0; n-3/n-6 = 0.02 for
the control group, 0.2 for the test groups) for two weeks. The platelet
counts, platelet aggregation, and production of thromboxane A2 (TXA2),
plasma total cholesterol (TC) and triacylglycerols (TG) were not different
between the ALA group and the control group, but showed a decreasing
tendency for the EPA group and significant decreases for the DHA group. The
production of prostacyclin in the aorta was significantly decreased in all
of the n-3 PUFA groups when compared with that in the control group. Liver
TC and TG concentrations were significantly decreased in the DHA group when
compared with those in the control group. Based on the above, it is assumed
that the physiological action exerted by n-3 PUFA differs by type and that
DHA is a more effective n-3 PUFA, both for suppressing platelet aggregation
and for modulating lipid metabolism in the plasma and liver of rats.
PMID: 9675708 [PubMed - indexed for MEDLINE]
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Dietary n-3 fatty acids influence the lipid composition
and physical properties of liver microsomal membranes in diabetic rats.
Igal A, de Gomez Dumm NT.
Instituto de Investigaciones Bioquimicas de La Plata (INIBIOLP), Universidad
Nacional de La Plata, Facultad de Ciencias Medicas, Argentina.
We examined the effect of n-3 fatty acid consumption on the lipid
composition and physical properties of liver microsomal membranes in normal
and experimental diabetic rats. Lipid analysis showed a significant increase
in the cholesterol:phospholipid ratio in membranes of normal animals fed n-3
fatty acids as well as in both groups of diabetic rats. These changes would
be in part responsible for the higher fluorescent polarization of DPH
(1,6-diphenyl-1,3,5 hexatriene) observed in the diabetic groups compared
with the normal ones. These alterations were partially compensated by an
increase in the amount of phosphatidylcholine in the diabetic rats fed on
n-3 fatty acids. However, proteins also play a role in determining the
physical properties of the liver microsomes because in the liposomes derived
from them, the fluorescent polarization of DPH decreased in the diabetics
fed n-3 fatty acids. Measurements of fluorescence anisotropy of n-AS (2-, 7
and 12 (9 anthroyloxy) stearic acid) probes revealed a restricted rotational
mobility in the middle zone of the bilayer. Consistently with this finding
there was an elevation in the calculated unsaturation density of the fatty
acids at the carbon 8 position. These experiments confirm the lipid
abnormalities that take place in experimental diabetes and they show further
that n-3 fatty-acid administration causes certain compensatory, and thus
beneficial, changes in these abnormalities.
PMID: 9089807 [PubMed - indexed for MEDLINE]
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n-3 fatty acids and serum lipoproteins: animal studies.
Harris WS.
Metabolism and Vascular Research Laboratory, Mid America Heart Institute, St
Luke's Hospital, Kansas City, MO 64111, USA. wharris@saint-lukes.org
This review examines the effects of n-3 fatty acids on serum lipid and
lipoprotein concentrations in seven species of experimental animals. n-3
Fatty acids consistently lower serum triacylglycerol concentrations in
humans but not in most animals. In addition, a common effect of n-3 fatty
acids in animals is a marked reduction in
high-density-lipoprotein-cholesterol concentrations, a response virtually
never seen with fish-oil supplementation in humans. These differences
between animals and humans arise not only from underlying species
differences in lipoprotein metabolism but also from differences in
experimental designs, the most notable of which is the tendency to feed
animals much larger amounts of n-3 fatty acids than supplements provide for
humans. Thus, great care must be taken not only to use appropriate animal
models when studying lipoprotein metabolism but also to feed the animals
comparable amounts of n-3 fatty acids. Failure to properly address these
issues will make it difficult to uncover the biochemical basis for the
hypolipidemic effect of fish oils in humans through use of experimental
animals.
Publication Types:
PMID: 9129501 [PubMed - indexed for MEDLINE]
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Dietary long-chain polyunsaturated fatty acids influence
tissue fatty acid composition in rats at weaning.
Suarez A, del Carmen Ramirez M, Faus MJ, Gil A.
Department of Biochemistry and Molecular Biology, Instituto de Nutricion y
Technologia de los Alimentos, University of Granada, Spain.
We studied the fatty acid composition of plasma, plasma phospholipids,
erythrocyte membrane lipids, liver microsomal phospholipids and brain lipids
in rats fed three different diets varying in their (n-3) and (n-6)
long-chain polyunsaturated fatty acid (LCP) concentrations for 0, 2 and 4 wk
after weaning. The three diets contained 10% fat; diet HO had a high-oleic
acid proportion; diet FO was enriched in n-3 LCP provided by fish oil; and
diet FO + BPL contained n-3 and n-6 LCP supplied by fish oil and a brain
phospholipid concentrate. At 2 and 4 wk after weaning the proportions of
oleic acid in all tissues, except in liver microsomes of the FO + BPL group,
were significantly higher than in weanling rats. The absence of (n-3) LCP
intake resulted in significantly lower levels of docosapentaenoic
[20:5(n-3)] and 22:6(n-3) acids in plasma, plasma phospholipids, erythrocyte
membrane lipids and liver microsomal phospholipids but not in brain lipids
compared with rats at weaning. Dietary supplementation with (n-3) LCP (FO
and FO + BPL groups) for 4 wk led to higher levels of 22:6(n-3) in all
tissues compared with rats fed the HO fat. The proportions of 20:4(n-6) and
total (n-6) LCP were significantly lower in all tissues from rats fed the FO
diet than in rats at weaning and rats fed the HO diet. After 2 and 4 wk,
rats fed the FO + BPL diet had significantly higher levels of 20:4(n-6) and
total (n-6) LCP in plasma, plasma phospholipids, erythrocyte lipids and
liver microsomal phospholipids; the brain also showed a higher content of
those fatty acids after 4 wk. Our results suggest that dietary
supplementation with 20:4(n-6) and 22:6(n-3) influences the concentration of
20:4-(n-6) and 22:6(n-3) in body tissues of rats after weaning.
PMID: 8613892 [PubMed - indexed for MEDLINE]
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Dietary n-6 fatty acids inhibit the incorporation of
dietary n-3 fatty acids in thrombocyte and serum phospholipids in humans: a
controlled dietetic study.
Gronn M, Gorbitz C, Christensen E, Levorsen A, Ose L, Hagve TA,
Christophersen BO.
Institute of Clinical Biochemistry, Rikshospitalet, Oslo, Norway.
The effect of a high dietary intake of n-6 fatty acids (36 g daily) vs a low
intake (4-6 g daily) on the incorporation of fatty acids from a dietary
supplementation of n-3 fatty acids (6 g daily) was studied for 8 weeks in 15
healthy, normolipaemic volunteers. The importance of a high (43.6) vs a low
(20.6) energy percentage from fat was also investigated in the participants
on a low n-6 intake. Fatty acid analyses of serum and thrombocyte
phospholipids showed a marked increase in docosahexaenoic acid (22:6 (n-3),
DHA) and especially eicosapentaenoic acid (20:5 (n-3), EPA) in both the high
and low n-6 groups after 14 days, but the changes were significantly greater
in the low n-6 diet groups. Changes of the ratio between EPA and arachidonic
acid (20:4 (n-6), AA) in phospholipids followed an identical pattern in
serum and thrombocytes. This indicates that thrombocytes are influenced by
the fatty acid composition in serum. The results showed that incorporation
of n-3 fatty acids in phospholipids was reduced by a high intake of dietary
n-6 fatty acids in the cells and lipid fractions studied. The observed
effect of dietary n-6 fatty acids was independent of the energy percentage
provided by dietary fat. In order to obtain an optimal effect of n-3
supplementation, the intake of linoleic acid has to be considered and kept
at a low level. The serum content of cholesterol was unaffected, but the
concentration of triacylglycerol was reduced during the supplementation
period.
PMID: 1909049 [PubMed - indexed for MEDLINE]
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Transfer of n-3 and n-6 polyunsaturated fatty acids from
yolk to embryo during development of the king penguin.
Decrock F, Groscolas R, McCartney RJ, Speake BK.
Centre d'Ecologie et Physiologie Energetiques, Centre National de la
Recherche Scientifique, Associe a l'Universite Louis Pasteur, 67087
Strasbourg, France.
This study examines the transfer of lipids from the yolk to the embryo of
the king penguin, a seabird with a high dietary intake of n-3 fatty acids.
The concentrations of total lipid, triacylglycerol (TAG), and phospholipid
(PL) in the yolk decreased by ~80% between days 33 and 55 of development,
indicating intensive lipid transfer, whereas the concentration of
cholesteryl ester (CE) increased threefold, possibly due to recycling. Total
lipid concentration in plasma and liver of the embryo increased by twofold
from day 40 to hatching due to the accumulation of CE. Yolk lipids contained
high amounts of C(20-22) n-3 fatty acids with 22:6(n-3) forming 4 and 10% of
the fatty acid mass in TAG and PL, respectively. Both TAG and PL of plasma
and liver contained high proportions of 22:6(n-3) ( approximately 15% in
plasma and >20% in liver at day 33); liver PL also contained a high
proportion of 20:4(n-6) (14%). Thus both 22:6(n-3) and 20:4(n-6), which are,
respectively, abundant and deficient in the yolk, undergo biomagnification
during transfer to the embryo.
PMID: 11171665 [PubMed - indexed for MEDLINE]
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Docosahexaenoic acid is the preferred dietary n-3 fatty
acid for the development of the brain and retina.
Anderson GJ, Connor WE, Corliss JD.
Department of Medicine, Oregon Health Sciences University, Portland 97201.
The metabolism of individual dietary n-3 fatty acids was studied in n-3
fatty acid-deficient newly hatched chicks. Laying hens were fed the n-6
fatty acid, ethyl linoleate, as the only source of polyunsaturated fat.
Chicks were then fed the n-3-deficient hens' diet, or one of three other
diets supplemented with the ethyl ester of 18:3 n-3, 20:5 n-3 [eicosapentaenoic
acid (EPA)], or 22:6 n-3 [docosahexaenoic acid (DHA)] at 0.44% of calories.
At the end of 0, 1, 2, and 3 wk, the fatty acid composition of the brain,
retina, liver, and serum was determined. Dietary EPA and DHA were equally
effective at raising levels of DHA in the brain and retina. Dietary 18:3 was
relatively ineffective in restoring brain and retina DHA. In the
n-3-deficient chicks fed EPA or DHA, levels of DHA recovered to control
values in both the brain and retina by 3 wk. Very little EPA accumulated in
the brain or retina of chicks fed EPA. Hepatic synthesis of DHA from EPA
appeared low, suggesting that the brain and retina synthesized the DHA that
accumulated rapidly in these tissues after the feeding of EPA. The
delta-4-desaturase enzyme was apparently very active, then, in the brain and
retina. Retroconversion of dietary 22:6 to 22:5 and 20:5 was evident in the
serum, liver, and retina but not in the brain. Thus, it was possible to
study the relative metabolism and especially the interconversion of n-3
fatty acids in a environment uncomplicated by existing stores of these
essential fatty acids. This study would suggest that 18:3 as the sole source
of n-3 fatty acids in the diets of animals, including the human infant, may
not be adequate for the biochemical development of the brain and retina and
that dietary DHA is the preferred fatty acid of the n-3 series.
PMID: 2136947 [PubMed - indexed for MEDLINE]
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Decrease of brain phospholipid synthesis in free-moving
n-3 fatty acid deficient rats.
Gazzah N, Gharib A, Croset M, Bobillier P, Lagarde M, Sarda N.
INSERM U. 352, INSA-Lyon, Villeurbanne, France.
The autoradiographic method with [14C]-docosahexaenoic acid ([14C]22:6 n-3)
was used to determine whether a diet deficient in n-3 fatty acids, inducing
a decrease in 22:6 n-3 circulating level, was associated with changes in
local rates of phospholipid synthesis in the rat brain. As compared with
rats fed a normal diet (peanut plus rapeseed oil), a n-3 fatty acid
deficiency [peanut oil group (P group)] induced a generalized decrease (-35
to -76%) of 22:6 n-3 incorporation rates into phospholipids in all the
regions examined. This effect was confirmed by using [3H]22:6 n-3 infusion
by biochemical analysis and quantifications corrected for the contribution
of docosahexaenoate derived from lipid store recycling to the unesterified
pool, taken as the precursor pool for phospholipid synthesis in the whole
brain. In normal or n-3 fatty acid-deficient rats, the values of the
brain-to-plasma 22:6 n-3 specific activity ratio (psi) were similar (0.03),
indicating that a considerable endogenous source of 22:6 n-3 (97%), likely
derived from phospholipid degradation, dilutes the specific activity of the
tracer coming from plasma. Using the specific activity of 22:6 n-3 in plasma
instead of brain would thus lead to a gross underestimation of the rate of
phospholipid synthesis. The results also demonstrate that the pattern of 14C
or 3H distribution in brain lipids was not modified by the n-3 fatty
acid-deficient diet. The major lipids labeled were phospholipids,
particularly phosphatidylethanolamine. Nevertheless, the unesterified 22:6
n-3 concentrations in plasma and brain were significantly reduced (eight-and
threefold, respectively) in the P group. In addition, the proportion of 22:6
n-3 in the brain total lipid fraction, total phospholipids, and
phosphatidylcholine, -ethanolamine, and -serine was significantly decreased
in n-3 fatty acid-deficient rats. This was partially compensated for by an
increase in the 22:5 n-6 level. These results are discussed in relation to
the limitation of 22:6 n-3 use to quantify, by the quantitative
autoradiographic method, changes in local rates of phospholipid synthesis in
rat brain.
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The ratio of dietary (n-6) to (n-3) fatty acids
influences immune system function, eicosanoid metabolism, lipid peroxidation
and vitamin E status in aged dogs.
Wander RC, Hall JA, Gradin JL, Du SH, Jewell DE.
Department of Nutrition and Food Management, Oregon State University,
Corvallis 97331-5103, USA.
We studied the effects of feeding experimental diets containing (n-6) to
(n-3) fatty acid ratios of 31:1, 5.4:1, and 1.4:1 to 20 healthy female
geriatric Beagles (9.5-11.5 y) for 8-12 wk on various indices of the immune
response. Compared with the 31:1 diet, consumption of the 5.4:1 and 1.4:1
diets significantly increased (n-3) fatty acids in plasma (2.17 +/- 0.64,
9.05 +/- 0.64, 17.46 +/- 0.64 g/100 g fatty acids, respectively, P <
0.0001). Although supplementation with (n-3) fatty acids did not
significantly alter the humoral immune response to keyhole limpet hemocyanin
(KLH), it significantly suppressed the cell-mediated immune response based
on results of a delayed-type hypersensitivity (DTH) skin test. The DTH
response after intradermal injection of KLH at 24 h was significantly lower
in the group consuming the 1.4:1 diet compared with the group consuming the
5.4:1 (P = 0.02) or the 31:1 diets (P = 0.04), and remained significantly
suppressed at 48 h in the group fed 1.4:1 relative to the group fed 31:1.
After consumption of the 1.4:1 diet, stimulated mononuclear cells produced
52% less prostaglandin E2 (PGE2) than those from dogs fed the 31:1 diet (224
+/- 74 and 451 +/- 71 pmol/L, respectively, P = 0.04). Plasma concentration
of alpha-tocopherol was 20% lower in dogs fed the 1.4:1 diet compared with
those fed the 31:1 diet (P = 0.04), and lipid peroxidation was greater in
both plasma (P = 0.03) and urine (P = 0.002). These data suggest that
although a ratio of dietary (n-6) to (n-3) fatty acids of 1.4:1 depresses
the cell-mediated immune response and PGE2 production, it increases lipid
peroxidation and lowers vitamin E concentration.
PMID: 9187636 [PubMed - indexed for MEDLINE]
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Effects of dietary n-3/n-6 and polyunsaturated fatty
acid/saturated fatty acid ratios on platelet aggregation and lipid
metabolism in rats.
Yamada N, Takita T, Wada M, Kannke Y, Innami S.
Department of Nutrition, Faculty of Agriculture, Tokyo University of
Agriculture, Japan.
We studied the effects of dietary lipids on platelet aggregation and lipid
metabolism in rats by varying the n-3/n-6 ration while maintaining the
polyunsaturated fatty acid/saturated fatty acid (P/S) ratio fixed, and vice
versa. After two weeks, the platelet counts decreased as the dietary n-3/n-6
ratio rose, and platelet aggregation was sufficiently suppressed at the
ratio of 0.2. Differences in the dietary P/S ratio, however, did not affect
either the platelet counts nor platelet aggregation. As the dietary n-3/n-6
ratio rose, the proportion of arachidonic acid (AA) in the plasma and the
phospholipids (PL) of the platelets and aorta decreased gradually, whereas
the proportion of eicosapentaenoic acid (EPA) in each tissue increased
gradually. The proportion of EPA was higher in the platelets than in the
aorta, while that of docosahexaenoic acid (DHA) was higher in the latter.
The production of platelet thromboxane A2 (TXA2) and aortic prostacyclin
(PGI2) showed sharp declines, from the values for the n-3/n-6 ratio of 0.02
(control) to those for 0.5. These results suggest that the n-3/n-6 ratio of
dietary fats necessary to ensure the suppression of platelet aggregation in
normal rats would be at least 0.2 and no more than 0.5.
PMID: 8981249 [PubMed - indexed for MEDLINE]
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Effects of long-chain monounsaturated and n-3 fatty acids
on fatty acid oxidation and lipid composition in rats.
Halvorsen B, Rustan AC, Madsen L, Reseland J, Berge RK, Sletnes P,
Christiansen EN.
Institute for Nutrition Research, University of Oslo, Norway.
Long-chain n-3 fatty acids and fat fish are reported, among multiple
physiological properties, to enhance peroxisomal beta-oxidation and effect
triacylglycerol status. Long-chain n-3 and monounsaturated fatty acids are
the main portion of fatty acids in fat fish. The individual effect of
long-chain monounsaturated fatty acids on beta-oxidation and fatty acid
composition was tested and compared to the effect of n-3 polyunsaturated and
saturated fatty acids in a 3-week feeding experiment of rats. To explore the
contribution from long-chain monounsaturated fatty acids in these aspects,
the effect of long-chain n-3 and monounsaturated fatty acids on
mitochondrial and peroxisomal beta-oxidation was compared, as well as fatty
acid composition of adipose tissue, liver and serum. Fatty acid oxidase,
palmitoyltransferase I and II activities, the amount of serum lipids, and
the fatty acid composition of lipid fractions from the organs were analysed.
The peroxisomal beta-oxidation was enhanced by the n-3 fatty acids, whereas
a small, significant increase with the monounsaturated fatty acids was
observed. There was a stimulation of the mitochondrial oxidation with the
n-3 fatty acids, but monounsaturated fatty acids gave a small,
nonsignificant decrease. With n-3 fatty acids there was a considerable
decrease in the levels of serum triacylglycerol, phospholipids, free fatty
acids and total cholesterol, while there were only minor effects of
monounsaturated fatty acids. As judged from the fatty acid composition data,
there was a mobilization on n-3 fatty acids from the adipose tissue to liver
and plasma with the n-3 diet. This observation was also seen with the
monounsaturated fatty acid-enriched diet. In conclusion, monounsaturated
fatty acids seemed to stimulate peroxisomal beta-oxidation and to increase
plasma triacylglycerol, whereas the mitochondrial oxidation was slightly
decreased. Copyright 2001 S. Karger AG, Basel.
PMID: 11244185 [PubMed - indexed for MEDLINE]
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Effect of diet on the rate of depletion of n-3 fatty
acids in the retina of the guinea pig.
Weisinger HS, Vingrys AJ, Abedin L, Sinclair AJ.
Department of Optometry, University of Melbourne, Parkville, Victoria,
Australia.
This study has assessed the influence of maternal n-3 long chain
polyunsaturated fatty acid supply and dietary manipulation after weaning on
the retinal polyunsaturated fatty acid profile. Infant guinea pigs born of
dams fed one of two commercial chow diets (differing in the amount of
eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) were raised
in two separate experiments, and subsequently partitioned into two diet
groups, one supplied with a high level of alpha-linolenic acid (canola oil
supplemented), the other with a very low level of alpha-linolenic acid
(safflower oil supplemented). Guinea pigs born of dams supplied with the
longer chain n-3 fatty acids in the commercial pellets (experiment 2) showed
higher levels of retinal docosahexaenoic acid at weaning compared with those
born to dams fed chow containing only alpha-linolenic acid (experiment 1).
The rate of depletion of retinal docosahexaenoic acid after weaning onto the
safflower oil diet was described by a two-stage exponential decay, possibly
reflecting systemic and local conservation mechanisms, in conditions of
dietary n-3 fatty acid deprivation. The rate of docosahexaenoic acid
depletion in the group with the lower retinal docosahexaenoic acid at
weaning was more than double the rate of depletion in the group with the
higher weaning docosahexaenoic acid value. The endpoint retinal
docosahexaenoic acid level at 16 weeks post-weaning after dietary n-3 fatty
acid depletion on the safflower oil diet in the group, which started with
the lower retinal docosahexaenoic acid level, was approximately half that
compared with the group from the dams fed long chain n-3 fatty acids
(experiment 1, 5% (interpolated), experiment 2, 9%). These results suggest
that an adequately supplied mother is capable of providing an infant with
enough n-3 fatty acids to withstand a longer period of dietary deprivation
imposed after weaning.
PMID: 9643359 [PubMed - indexed for MEDLINE]
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The effects of n-3 fatty acid deficiency and repletion
upon the fatty acid composition and function of the brain and retina.
Connor WE, Neuringer M.
Department of Medicine, Oregon Health Sciences University, Portland 97201.
It is now apparent that both n-6 and n-3 fatty acids are essential for
normal development in mammals, and that each has specific functions in the
body. N-6 fatty acids are necessary primarily for growth, reproduction, and
the maintenance of skin integrity, whereas n-3 fatty acids are involved in
the development and function of the retina and cerebral cortex and perhaps
other organs such as the testes. Fetal life and infancy are particularly
critical for the nervous tissue development. Therefore, with respect to
human nutrition, adequate amounts of omega-3 fatty acids should be provided
during pregnancy, lactation and infancy, but probably throughout life. We
estimate that adequate levels are provided by diets containing 6-8% kcals
from linoleic acid and 1% from n-3 fatty acids (alpha-linolenic acid, EPA
and DHA), resulting in a ratio of n-6 to n-3 fatty acids of 4:1 to 10:1. The
essentiality of n-3 fatty acids resides in their presence as DHA in vital
membranes of the photoreceptors of the retina and the synaptosomes and other
subcellular membranes of the brain. The replacement of DHA in deficient
animals by the n-6 fatty acid, 22:5, results in abnormal functioning of the
membranes for reasons as yet to be ascertained. Most significant is the
lability of fatty acid composition in the retinal and brain of deficient
animals. Dietary fish oil, which contains EPA and DHA, will readily lead to
a change in the composition of the membrane of retina and brain, fatty
acids, with DHA replacing the n-6 fatty acid, 22:5. The interrelationships
between the chemistry of neural and retinal membranes as affected by diet
and their biological functioning provides an exciting prospect for future
investigations.
PMID: 3241811 [PubMed - indexed for MEDLINE]
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Effects of dietary fatty-acid supplementation on
fatty-acid composition and deformability of young and old erythrocytes.
Mills DE, Galey WR, Dixon H.
Department of Health Studies, University of Waterloo, Ontario, Canada.
The effects of cell age on erythrocyte phospholipid fatty-acid composition
and deformability were examined in 20 healthy adults (11 male, 9 female)
prior to and following 12 weeks of dietary supplementation with 3.5 g/day of
safflower oil (high in n - 6 fatty acids) or fish oil (high in n - 3 fatty
acids). In the absence of dietary supplementation, old erythrocytes
demonstrated an increase in filtration time (P < 0.001), an increase in
membrane phospholipid total n - 6 fatty acids (P < 0.01), and a decrease
in total n - 3/total n - 6 ratio (P < 0.01) compared to young
erythrocytes. Both safflower and fish oil supplementation attenuated
age-related differences in membrane phospholipid total n - 6 and total n - 3
fatty acids. Fish oil supplementation also increased the proportion of n - 3
fatty acids (P < 0.01) and the n - 3/n - 6 ratio (P < 0.05) in the
phospholipids of both young and old erythrocytes, and eliminated age-related
differences in erythrocyte filtration time by reducing the relative
filtration time of the old erythrocytes.
PMID: 8323949 [PubMed - indexed for MEDLINE]
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Brain phospholipids as dietary source of (n-3)
polyunsaturated fatty acids for nervous tissue in the rat.
Bourre JM, Dumont O, Durand G.
Institut National de la Sante et de la Recherche Medicale, INSERM Unite 26,
Hopital Fernand Widal, Paris, France.
In a previous work, we calculated the dietary alpha-linolenic requirements
(from vegetable oil triglycerides) for obtaining and maintaining a
physiological level of (n-3) fatty acids in developing animal membranes as
determined by the cervonic acid content [22:6(n-3), docosahexaenoic acid].
The aim of the present study was to measure the phospholipid requirement, as
these compounds directly provide the very long polyunsaturated fatty acids
found in membranes. Two weeks before mating, eight groups of female rats
(previously fed peanut oil deficient in alpha-linolenic acid) were fed
different semisynthetic diets containing 6% African peanut oil supplemented
with different quantities of phospholipids obtained from bovine brain lipid
extract, so as to add (n-3) polyunsaturated fatty acids to the diet. An
additional group was fed peanut oil with rapeseed oil, and served as
control. Pups were fed the same diet as their respective mothers, and were
killed at weaning. Forebrain, sciatic nerve, retina, nerve endings, myelin,
and liver were analyzed. We conclude that during the combined maternal and
perinatal period, the (n-3) fatty acid requirement for adequate deposition
of (n-3) polyunsaturated fatty acids in the nervous tissue (and in liver) of
pups is lower if animals are fed (n-3) very long chain polyunsaturated fatty
acids found in brain phospholipids [this study, approximately 60 mg of (n-3)
fatty acids/100 g of diet, i.e., approximately 130 mg/1,000 kcal] rather
than alpha-linolenic acid from vegetable oil triglycerides [200 mg of (n-3)
fatty acids/100 g of diet, i.e., approximately 440 mg/1,000 kcal].
PMID: 8492115 [PubMed - indexed for MEDLINE
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Serum lipids, hepatic glycerolipid metabolism and
peroxisomal fatty acid oxidation in rats fed omega-3 and omega-6 fatty
acids.
Rustan AC, Christiansen EN, Drevon CA.
Institute for Nutrition Research, University of Oslo, Norway.
Rats were fed, for 3 weeks, high-fat (20% w/w) diets containing
sunflower-seed oil, linseed oil or fish oil. Chow-fed rats were used as a
low-fat reference. The high-fat diets markedly reduced non-fasting-rat serum
triacylglycerol as compared with the low-fat reference, and the highest
reduction (85%) was observed with the fish-oil group, which was
significantly lower than that of the other high-fat diets. The serum
concentration of phospholipids was significantly reduced (30%) only in the
fish-oil-fed animals, whereas serum non-esterified fatty acids were reduced
40-50% by both the fish-oil- and linseed-oil-fed groups. The liver content
of triacylglycerol showed a 1.7-fold increase with the fish-oil diet and
2-2.5-fold with the other dietary groups when compared with rats fed a
low-fat diet, whereas the hepatic content of phospholipids was unchanged.
Peroxisomal fatty acid oxidation (acyl-CoA oxidase) was 2-fold increased for
the rats fed fish oil; however this was not significantly higher when
comparison was made with rats fed the linseed-oil diet. There was no
difference in phosphatidate hydrolysis (microsomal and cytosolic fractions)
among animals fed the various diets. Acyl-CoA:diacylglycerol acyltransferase
activity was increased by all high-fat diets, but the fish-oil-diet-fed
group showed a significantly lower enzyme activity than did rats fed the
other high-fat diets. A linear correlation between acyl-CoA:diacylglycerol
acyltransferase activity and liver triacylglycerol was observed, and the
microsomal enzyme activity was decreased 40-50% by incubation in the
presence of eicosapentaenoyl-CoA. CoA derivatives of arachidonic, linolenic
and linoleic acid had no inhibitory effect when compared with the control.
These results indicate that dietary fish oil may have greater
triacylglycerol-lowering effect than other polyunsaturated diets, owing to
decreased triacylglycerol synthesis caused by inhibition of
acyl-CoA:diacylglycerol acyltransferase. In addition, increased peroxisomal
fatty acid oxidation and decreased availability of non-esterified fatty
acids could also contribute by decreasing the amounts of fatty acids as
substrates for triacylglycerol synthesis and secretion.
PMID: 1349473 [PubMed - indexed for MEDLINE]
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