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1.
Fatty acids,the immune response,and autoimmunity: A question of n−6 essentiality and the balance between n−6 and n−3 总被引:8,自引:0,他引:8
Harbige LS 《Lipids》2003,38(4):323-341
The essentiality of n−6 polyunsaturated fatty acids (PUFA) is described in relation to a thymus/thymocyte accretion of arachidonic
acid (20∶4n−6, AA) in early development, and the high requirement of lymphoid and other cells of the immune system for AA
and linoleic acid (18∶2n−6, LA) for membrane phospholipids. Low n−6 PUFA intakes enhance whereas high intakes decrease certain
immune functions. Evidence from in vitro and in vivo studies for a role of AA metabolites in immune cell development and functions shows that they can limit or regulate cellular
immune reactions and can induce deviation toward a T helper (Th)2-like immune response. In contrast to the effects of the
oxidative metabolites of AA, the longer-chain n−6 PUFA produced by γ-linolenic acid (18∶3n−6, GLA) feeding decreases the Th2
cytokine and immunoglobulin (Ig)G1 antibody response. The n−6 PUFA, GLA, dihomo-γ-linolenic acid (20∶3n−6, DHLA) and AA, and
certain oxidative metabolites of AA can also induce T-regulatory cell activity, e.g., transforming growth factor (IGF)-β-producing
T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)-1 and tumor necrosis factor (TNF)-α
production. Low intakes of long-chain n−3 fatty acids (fish oils) enhance certain immune functions, whereas high intakes are
inhibitory on a wide range of functions, e.g., antigen presentation, adhesion molecule expression, Th1 and th2 responses,
proinflammatory cytokine and eicosanoid production, and they induce lymphocyte apoptosis. Vitamin E has a demonstrable critical
role in long-chain n−3 PUFA interactions with immune functions, often reversing the effects of fish oil. The effect of dietary
fatty acids on animal autoimmune disease models depends on both the autoimmune model and the amount and type of fatty acids
fed. Diets low in fat, essential fatty acid deficient (EFAD), or high in long-chain n−3 PUFA from fish oils increase survival
and reduce disease severity in spontaneous autoantibody-mediated disease, whereas high-fat LA-rich diets increase disease
severity. In experimentally induced T cell-mediated autoimmune disease, EFAD diets or diets supplemented with long-chain n−3
PUFA augment disease, whereas n−6 PUFA prevent or reduce the severity. In contrast, in both T cell- and antibody-mediated
autoimmune disease, the desaturated/elongated metabolites of LA are protective. PUFA of both the n−6 and n−3 families are
clinically useful in human autoimmune-inflammatory disorders, but the precise mechanisms by which these fatty acids exert
their clinical effects are not well understood. Finally, the view that all n−6 PUFA are proinflammatory requires revision,
in part, and their essential regulatory and developmental role in the immune system warrants appreciation. 相似文献
2.
The intake of individual n−6 and n−3 PUFA has been estimated in 4,884 adult subjects (2,099 men and 2,785 women), volunteers
from the French SU.VI.MAX intervention trial. The food intakes of each subject were recorded in at least ten 24-h record questionnaires
completed over a period of 2.5 yr, allowing the estimation of the daily intake of energy; total fat; and linoleic, α-linolenic,
arachidonic, eicosapentaenoic (EPA), n−3 docosapentaenoic (DPA), and docosahexaenoic (DHA) acids. The mean total fat intake
corresponded to 94.1 g/d (36.3% of total energy intake) in men and 73.4 g/d (38.1% of energy) in women. The intake of linoleic
acid was 10.6 g/d in men and 8.1 g/d in women, representing 4.2% of energy intake; that of α-linolenic acid was 0.94 g/d in
men and 0.74 g/d in women, representing 0.37% of energy intake, with a mean linoleic/α-linolenic acid ratio of 11.3. The mean
intakes of long-chain PUFA were: arachidonic acid, 204 mg/d in men and 152 mg/d in women; EPA, 150 mg/d in men and 118 mg/d
in women; DPA, 75 mg/d in men and 56 mg/d in women; DHA, 273 mg/d in men and 226 mg/d in women; long-chain n−3 PUFA, 497 mg/d
in men and 400 mg/d in women. Ninety-five percent of the sample consumed less than 0.5% of energy as α-linolenic acid, which
is well below the current French recommendation for adults (0.8% of energy). In contrast, the mean intakes of long-chain n−6
and n−3 PUFA appear fairly high and fit the current French recommendations (total long-chain PUFA: 500 mg/d in men and 400
mg/d in women; DHA: 120 mg/d in men and 100 mg/d in women). The intakes of α-linolenic acid, and to a lesser extent of linoleic
acid, were highly correlated with that of lipids. Whereas the main source of linoleic acid was vegetable oils, all food types
contributed to α-linolenic acid intake, the main ones being animal products (meat, poultry, and dairy products). The main
source of EPA and DHA (and of total long-chain n−3 PUFA) was fish and seafood, but the major source of DPA was meat, poultry,
and eggs. Fish and seafood consumption showed very large interindividual variations, the low consumers being at risk of insufficient
n−3 PUFA intake. 相似文献
3.
A single-cell oil from a Mortierella alpina mutant (TGM17 oil) contains n−9 PUFA: 14.3 wt% 6,9-octadecadienoic acid (18∶2n−9; n−9 LnA) and 17.1 wt% Mead acid (20∶3n−9;
MA). Lipase screening indicated that Pseudomonas aeruginosa lipase acted strongly on n−9 LnA and weakly on MA, and Candida rugosa lipase acted weakly on the two PUFA. Hence, fractionation and enrichment of the two FA were conducted with the lipases. The
first step was selective hydrolysis of IGM17 oil with P. aeruginosa lipase. The hydrolysis fractionated the oil into FFA containing 20.4 wt% n−9 LnA and 6.3 wt% MA, and acylglycerols containing
10.7 wt% n−9 LnA and 23.7 wt% MA. The FFA fraction was used for preparation of n−9 LnA-rich FFA. After removal of saturated
FA, the FFA were esterified with lauryl alcohol (LauOH) using C. rugosa lipase. Two selective esterifications increased the n−9 LnA content to 54.0 wt% with 38.2% recovery of the initial content
of TGM17 oil. The acylglycerol fraction obtained in the hydrolysis with P. aeruginosa lipase was used for preparation of MA-rich FFA. The acylglycerol fraction was hydrolyzed under alkaline conditions, and saturated
FA were eliminated by urea adduct fractionation. Two selective esterifications of the FFA with LauOH increased the MA content
to 60.2 wt% with 53.5% recovery. Thus, the two-step enzymatic process was effective for fractionation and enrichment of n−9
LnA and MA. 相似文献
4.
Effect of 18∶1n−9, 20∶5n−3, and 22∶6n−3 on lipid accumulation and secretion by atlantic salmon hepatocytes 总被引:1,自引:0,他引:1
We have studied the effects of dietary FA on the accumulation and secretion of [3H]glycerolipids by salmon hepatocytes in culture. Atlantic salmon were fed diets supplemented with either 100% soybean oil
(SO) or 100% fish oil (FO), and grew from an initial weight of 113±5 g to a final weight of 338 ±19 g. Hepatocytes were isolated
from both dietary groups and incubated with [3H]glycerol in an FA-free medium; a medium supplemented with 0.75 mM of one of three FA—18∶1n−9, 20∶5n−3, or 22∶6n−3—or a medium
supplemented with 0.75 mM of the sulfur-substituted FA analog tetradecylthioacetic acid (TTA), which cannot undergo β-oxidation.
Incubations were allowed to proceed for 1,2,6, or 24 h. The rate of the secretion of radioactive glycerolipids with no FA
added was 36% lower from hepatocytes isolated from fish fed the FO diet than it was from hepatocytes isolated from fish fed
the SO diet. Hepatocytes incubated with 18∶1n−9 secreted more [3H]TAG than when incubated with no FA, whereas hepatocytes incubated with 20∶5n−3 or TTA secreted less labeled TAG than when
incubated with no FA. This observation was independent of the feeding group. Hepatocytes incubated with 22∶6n−3 secreted the
highest amounts of total [3H]glycerolipids compared with the other treatments, owing to increased secretion of phospholipids and mono- and diacylglycerols
(MDG). In contrast, the same amounts of [3H]TAG were secreted from these cells as from cells incubated in an FA-free medium. The lipid-lowering effect of FO is thus
independent of 22∶6n−3, showing that 20∶5n−3 is the FA that is responsible for the lipid-lowering effect. The ratio of TAG
to MDG in lipids secreted from hepatocytes to which 20∶5n−3 or TTA had been added was lower than that in lipids secreted from
hepatocytes incubated with 18∶1n−9 or 22∶6n−3, suggesting that the last step in TAG synthesis was inhibited. Morphometric
measurements revealed that hepatocytes incubated with 20∶5n−3 accumulated significantly more cellular lipid than cells treated
with 18∶1n−9, 22∶6n−3, TTA, or no treatment. The area occupied by mitochondria was also greater in these cells. The present
study shows that dietary FO reduces TAG secretion from salmon hepatocytes and that 20∶5n−3 mediates this effect. 相似文献
5.
Effect of dietary n−6 and n−3 polyunsaturated fatty acids on peroxidizability of lipoproteins in steers 总被引:3,自引:0,他引:3
The susceptibility of major plasma lipoproteins to lipoperoxidation was studied in relation to the FA composition of their
neutral and polar lipids in steers given PUFA-rich diets. Two trials used, respectively, 18 (“sunflower” experiment, S) or
24 (“linseed” experiment, L) crossbred Salers x Charolais steers. Each involved three dietary treatments over a 70-d period:
a control diet (CS or CL diets) consisting of hay and concentrate, or the same diet supplemented with oilseeds (4% diet dry
matter) fed either as seeds (SS or LS diets) or continuously infused into the duodenum (ISO or ILO diets). Compared with control
diets, ISO and ILO treatments tended to decrease the resistance time of LDL and HDL classes to peroxidation, mainly owing
to the enrichment of their polar and neutral lipids with PUFA. With diets SS and LS, sensitivity of major lipoprotein classes
(LDL, light and heavy HDL) was not affected because ruminal hydrogenation of dietary PUFA decreased their incorporation into
lipoparticles. ISO and ILO treatments induced a more important production of conjugated dienes and hydroperoxides generated
by peroxidation in the three lipoprotein classes due to the higher amounts of PUFA esterified in lipids of the core and the
hydrophilic envelope of particles. The production of malondialdehyde (MDA) increased in steers fed linseed supplements, indicating
that MDA production did not occur with linoleic acid provided by sunflower oil supplements. Thus, plasma peroxidation of PUFA
generates toxic products in steers fed diets supplemented with PUFA and can be deleterious for the health of the animal during
long-term treatment. 相似文献
6.
Induction of apoptosis and apoptotic mediators in balb/C splenic lymphocytes by dietary n−3 and n−6 fatty acids 总被引:5,自引:0,他引:5
The present study was designed to investigate the effect of diatery n−6 and n−3 polyunsaturated fatty acids (PUFA) on anti-CD3
and anti-Fas antibody-induced apoptosis and its mediators in mouse spleen cells. Nutritionally adequate semipurified diets
containing either 5% w/w corn oil (n−6 PUFA) or fish oil (n−3 PUFA) were fed to weanling female Balb/C mice, and 24 wk later
mice were sacrificed. In n−3 PUFA-fed mice, serum and splenocyte lipid peroxides were increased by 20 and 28.3% respectively,
compared to n−6 PUFA-fed mice. Further, serum vitamin F levels were decreased by 50% in the n−3 PUFA-fed group, whereas higher
anti0Fas- and anti-CD3-induced apoptosis (65 and 66%) and necrosis (17 and 25%), compared to the n−6 PUFA-fed group, were
found when measured with Annexin V and propidium iodide staining, respectively. In addition, decreased Bcl-2 and increased
Fas-ligand (Fas-L) also were observed in the n−3 PUFA-fed group compared to the n−6 PUFA-fed group. No difference in the ratio
of splenocyte subsets nor their Fas expression was observed between the n−3 PUFA-fed and n−6 PUFA-fed groups, whereas decreased
proliferation of splenocytes was found in n−3 PUFA-fed mice compared to n−6 PUFA-fed mice. In conclusion, our results indicate
that dietary n−3 PUFA induces higher apoptosis by increasing the generation of lipid peroxides and elevating Fas-L expression
along with decreasing Bcl-2 expression. A reduced proliferative response of immune cells also was observed in n−3 PUFA-fed
mice. 相似文献
7.
We evaluated the utilization of α-linolenic acid (18∶3n−3) in growing rats consuming a diet deficient in n−6 PUFA. After 90
d, whole-body 18∶3n−3 accumulation was 55% lower, total n−3 PUFA accumulation was 21% lower, and 18∶3n−3 disappearance was
14% higher in n−6 PUFA-deficient rats. Part of the reduction of whole-body 18∶3n−3 in n−6 PUFA-deficient rats was due to the
25% increase in net conversion of 18∶3n−3 to long-chain n−3 PUFA. Despite adequate 18∶3n−3 intake, n−6 PUFA deficiency decreased
the accumulation of 18∶3n−3 and total n−3 PUFA. 相似文献
8.
Du ZY Demizieux L Degrace P Gresti J Moindrot B Liu YJ Tian LX Cao JM Clouet P 《Lipids》2004,39(9):849-855
Fish easily accumulate n−3 PUFA of exogenous origin, but the underlying mechanisms are not well established in the whole animal.
This study was undertaken to investigate whether this feature was physiologically associated with mitochondrial and peroxisomal
capacities that differentially affect FA oxidation. For this purpose, peroxisomal FA oxidation was increased by treating rainbow
trout with fenofibrate, which strongly stimulates the peroxisome proliferator-activated receptor-α in rodents. Diets containing
EPA and DHA, with or without fenofibrate added, were administered to male trout for 12 d. After treatment, neither liver hypertrophy
nor accumulation of fat was apparent within the liver and muscle cells. However, fenofibrate treatment decreased the contents
of EPA and DHA in the liver, white muscle, and intraperitoneal fat tissue, which represented (per whole body) at least 280
mg less than in controls. Carnitine-dependent palmitate oxidation rates, expressed per gram of liver, were slightly increased
by fenofibrate when measured from tissue homogenates and were unchanged when calculated from isolated mitochondria, relative
to control fish. The treatment altered neither carnitine palmitoyltransferase I activity rates, expressed per gram of liver,
nor the sensitivity of the enzyme to malonyl-CoA inhibition, but did increase the malonyl-CoA content (+45%). Meanwhile, fenofibrate
increased (by about 30%) the peroxisome-related activities, i.e, catalase, carnitine-independent palmitate oxidation, acyl-CoA
oxidase, and the peroxisomal FA-oxidizing system, relative to the control group. The data strongly suggest that the induction
of peroxisomal activities, some of which being able to oxidize very long chain FA, was responsible for the lower contents
of EPA and DHA in the body lipids of fenofibrate-treated trout. 相似文献
9.
Linoleic (18∶2n−6) and α-linolenic acids (18∶3n−3) have many important physiological functions including immunomodulation.
We tested how immunization influences the metabolism of 18∶2n−6 and 18∶3n−3 in the neck muscle of pigs. At 35 d old, pigs
received either an intramuscular neck injection containing hen egg white lysozyme (HEWL), killed Mycobacterium tuberculosis, and Freund’s complete adjuvant (immunized) or PBS (control). At 49 d old, immunized pigs received a booster injection of
HFWI and Freund’s incomplete adjuvant, and the control pigs received PBS into the neck. At 56 d old, all pigs received an
intradermal injection of Mycobacterium bovis into the hind leg to induce a delayed-type hypersensitivity (DTH) reaction. At 57 d old, immunized pigs had a twofold increase
in serum haptoglobin, a 10-fold increase in antibodies to HEWL, and the skinfold at the DTH reaction site was 10 times thicker
than the controls. Both 18∶2n−6 and 18∶3n−3 (% composition) were approximately 25% lower in muscle IG, 40% lower in FFA, 50%
lower in phospholipids, but not different in cholesteryl esters of the neck muscle of immunized pigs. The antigens in this
model induce an increased response in the innate (haptoglobin), humoral (antibodies), and cellular (DTH) immune systems as
well as a preferential decrease of 18∶2n−6 and 18∶3n−3 in the inflamed neck muscle. It appears that 18∶2n−6 and 18∶3n−3 are
preferentially metabolized (possibly β-oxidized) in response to antigens. 相似文献
10.
Oxidation, esterification, desaturation, and elongation of [1-14C]18∶2n−6 and [1-14C]18∶3n−3 were studied using hepatocytes from Atlantic salmon (Salmo salar I.) maintained on diets deficient in n−3 and n−6 polyunsaturated fatty acids (PUFA) or supplemented with n−3 PUFA. For both
dietary groups, radioactivity from 18∶3n−3 was incoporated into lipid fractions two to three times faster than from 18∶2n−6,
and essential fatty acids (FFA) deficiency doubled the incorporation. Oxidation to CO2 was very low and was independent of substrate or diet, whereas oxidation to acid-soluble products was stimulated by EFA deficiency.
Products from 18∶2n−6 were mainly 18∶3n−6, 20∶3n−6, and 20∶4n−6, with minor amounts of 20∶2n−6 and 22∶5n−6. Products from
18∶3n−3 were mainly 18∶4n−3, 20∶5n−3, and 22∶6n−3, with small amounts of 20∶3n−3. The percentage of 22∶6n−3 in the polar lipid
fraction of EFA-deficient hepatocytes was fourfold higher than in n−3 PUFA-supplemented cells. This correlated well with our
other results obtained after abdominal injection of [1-14C]18∶3n−3 and [1-14C]18∶2n−6. In hepatocytes incubated with [4,5-3H]-22∶6n−3, 20∶5n−3 was the main product. This retrocon-version was increased by EFA deficiency, as was peroxisomal β-oxidation
activity. This study shows that 18∶2n−6 and 18∶3n−3 can be elongated and desaturated in Atlantic salmon liver, and that this
conversion and the activity of retroconversion of very long chain PUFA is markedly enhanced by FFA deficiency. 相似文献
11.
Chapkin RS Hong MY Fan YY Davidson LA Sanders LM Henderson CE Barhoumi R Burghardt RC Turner ND Lupton JR 《Lipids》2002,37(2):193-199
There is experimental evidence that dietary fish oil, which contains the n−3 fatty acid family, i.e., EPA and DHA, protects
against colon tumor development, in part by increasing apoptosis. Since mitochondria can act as central executioners of apoptosis,
we hypothesized that EPA and DHA incorporation into colonocyte mitochondrial membranes, owing to their high degree of unsaturation,
would enhance susceptibility to damage by reactive oxygen species (ROS) generated via oxidative phosphorylation. This, in turn, would compromise mitochondrial function, thereby initiating apoptosis. To test
this hypothesis, colonic crypts were isolated from rats fed either fish oil, purified n−3 fatty acid ethyl esters, or corn
oil (control). Dietary lipid source had no effect on colonic mitochondrial phospholipid class mole percentages, although incorporation
of EPA and DHA was associated with a reduction in n−6 fatty acids known to enhance colon tumor development, i.e., linoleic
acid (LNA) and its metabolic product, arachidonic acid (ARA). Select compositional changes in major phospholipid pools were
correlated to alterations in mitochondrial function as assessed by confocal microscopy. The mol% sum of LNA plus ARA in cardiolipin
was inversely correlated with ROS (P=0.024). Ethanolamine glycerophospholipid ARA (P=0.046) and choline glycerophospholipid INA (P=0.033) levels were positively correlated to mitochondrial membrane potential. In contrast, ethanolamine glycerophospholipid
EPA (P=0.042) and DHA (P=0.024), levels were negatively correlated to mitochondrial membrane potential. Additionally, EPA and DHA levels in choline
glycerophospholipids (P=0.026) were positively correlated with caspase 3 activity. These data provide evidence in vivo indicating that dietary FPA and DHA induce compositional changes in colonic mitochondrial membrane phospholipids that facilitate
appotosis. 相似文献
12.
In this study, we examined the effect of dietary arachidonic acid (AA) and sesame lignans on the content and n-6/n-3 ratio
of polyunsaturated fatty acid (PUFA) in rat liver and the concentrations of triglyceride (TG) and ketone bodies in serum.
For 4 wk, rats were fed two types of dietary oils: (i) the control oil diet groups (CO and COS): soybean oil/perilla oil=5∶1,
and (ii) the AA-rich oil group (AO and AOS): AA ethyl esters/palm oil/perilla oil=2∶∶1, with (COS and AOS) or without (CO
and AO) 0.5% (w/w) of sesame lignans. Dietary AA and sesame lignans significantly affected hepatic PUFA metabolism. AA content
and n-6/n-3 ratio in the liver were significantly increased in the AO group, despite the dietary total of n-6 PUFA being the
same in all groups, while AOS diet reduced AA content and n-6/n-3 ratio to a level similar to the CO and COS groups. These
results suggest that (i) dietary AA considerably affects the hepatic profile and n-6/n-3 ratio of PUFA, and (ii) dietary sesame
lignans reduce AA content and n-6/n-3 ratio in the liver. In the AO group, the concentration of acetoacetate was significantly
increased, but the ratio of β-hydroxybutyrate/acetoacetate was decreased. On the other hand, the AO diet increased the concentration
of TG in serum by almost twofold as compared to other groups. However, the AOS diet significantly reduced serum IG level as
compared to the AO group. In addition, the AOS diet signicantly increased the acetoacetate level, but reduced the β-hydroxybutyrate/acetoacetate
ratio. These results suggest that dietary sesame lignans promote ketogenesis and reduce PUFA esterification into TG. This
study resulted in two findings: (i) sesame lignans inhibited extreme changes of the n-6/n-3 ratio by reducing hepatic PUFA
content, and (ii) the reduction of hepatic PUFA content may have occurred because of the effects of sesame lignans on PUFA
degradation (oxidation) and esterification. 相似文献
13.
Artemis P. Simopoulos 《Lipids》2001,36(1):S83-S89
The last quarter of the 20th century was characterized by an increase in the consumer's interest in the nutritional aspects of health. As a result, governments began to develop dietary guidelines in addition to the traditional recommended dietary allowances, which have been superseded now by dietary reference intakes. In addition to governments, various scientific societies and nongovernmental organizations have issued their dietary advice to combat chronic diseases and obesity. Human beings evolved on a diet that was balanced in n?6 and n?3 essential fatty acid intake, whereas Western diets have a ratio of n?6/n?3 of 16.74. The scientific evidence is strong for decreasing the n?6 and increasing the n?3 intake to improve health throughout the life cycle. This paper discusses the reasons for this change and recommends the establishment of a nutrition and Food Policy, instead of a Food and Nutrition Policy, because the latter subordinates the nutritional aspects to the food policy aspects. Nutrition and food planning comprise a tool of nutrition and food policy, whose objectives are the achievement of the adequate nutrition of the population as defined by nutritional science. The scientific basis for the development of a public policy to develop dietary recommendations for essential fatty acids, including a balanced n?6/n?3 ratio is robust. What is needed is a scientific consensus, education of professionals and the public, the establishment of an agency on nutrition and food policy at the national level, and willingness of governments to institute changes. Education of the public is essential to demand changes in the food supply 相似文献
14.
In this study, a new marine oil that contains 45% docosahexaenoic acid (DHA, 22∶6n−3) and 13% docosapentaenoic acid (DPA,
22∶5n−6) was administered to rats. The metabolism and distribution of DPA in rats was investigated. In experiment 1, the effects
of DHA and n−6 fatty acids (linoleic acid, I A; arachidonic acid, AA; and DPA) on AA contents were investigated in vivo. LA group: LA 25%, DHA 30%; LA-DPA group: LA 15%, DPA 10%, DHA 35%; LA-AA-DPA group: LA 10%, AA 5%, DPA 10%, DHA 35% were
administered to rats for 4 wk. In the liver, the AA content in the LA-DPA and LA-AA-DPA groups was significantly higher than
in the LA group. The decreased AA contents in the LA group might be caused by DHA administration. Although DHA also was administered
in the LA-DPA and LA-AA-DPA groups, the AA contents in these two groups did not decrease. These results suggested that DPA
retroconverted to AA, blunting the decrease in AA content caused by DHA administration. To conduct a detailed investigation
on DPA metabolism and its relation with AA and DHA, rat hepatocytes were cultured with pruified DPA and DHA for 24 h. We discovered
the retroconversion of DPA to AA occurred only when AA content was decreased by a high DHA administration; it did not occur
when AA content was maintained at a normal level. 相似文献
15.
The effect of N-ethyl-maleimide (NEM) on Δ5-and Δ6-desaturase activities and the incorporation of substrates and products into different
microsomal lipid classes and phospholipid (PL) subclasses were studied in human fetal liver microsomes, obtained after legally
approved therapeutic abortion. Desaturase activities were measured by a radiochemical method using reversed-phase high-performance
liquid chromatography (HPLC). After nonphospholipid (NPL) and PL separation on silica cartridges, the radioactivity in different
lipids of the NPL group was assessed by two-dimensional thin-layer chromatography, and their fatty acid (FA) composition by
gas-liquid chromatography. The PL subclasses were separated, and the distribution of radioactivity between products and substrates
was determined in PL subclasses. NEM inhibited the Δ5- and Δ6-desaturase activities in the n−6 series of FA but not the Δ6-desaturase
activity in the n−3 series, which suggests the existence of two distinct Δ6-desaturases, one for the n−6 series and another
for the n−3 series. Whether NEM was present or absent, most of the radioactivity was recovered in the free FA form (about
80%). The desaturation products, obtained in the presence or absence of NEM, were preferentially incorporated into PL, suggesting
a channeling of the newly synthesized FA toward microsomal PL. The comparison of the distribution of substrates and products
incorporated into the different PL classes showed that most of the labeled FA were incorporated into phosphatidylcholine and
to a lesser degree into phosphatidylethanolamine. 相似文献
16.
Male Fischer rats were fed the AIN76A diet containing varying n−6/n−3 FA ratios using sunflower oil (SFO), soybean oil (SOY),
and SFO supplemented with EPA-50 and GLA-80 (GLA) as fat sources. Hepatocyte nodules, induced using diethylnitrosamine followed
by 2-acetylaminofluorene/partial hepatoctomy promotion, were harvested, with surrounding and respective dietary control tissues,
3 mon after partial hepatectomy. The altered growth pattern of hepatocyte nodules in rats fed SFO is associated with a distinct
lipid pattern entailing an increased concentration of PE, resulting in increased levels of 20∶4n−6. In addition, there is
an accumulation of 18∶1n−9 and 18∶2n−6 and a decrease in the end products of the n−3 metabolic pathway in PC, suggesting a
dysfunctional Δ-6-desaturase enzyme. The hepatocyte nodules of the SFO-fed rats exhibited a significantly reduced lipid peroxidation
level that was associated with an increaser in the glutathione (GSH) concentration. The low n−6/n−3 FA ratio diets significantly
decreased 20∶4n−6 in PC and PE phospholipid fractions with a concomitant increase in 20∶5n−3, 22∶5n−3, and 22∶6n−3. The resultant
changes in the 20∶4/20∶5 FA ratio and the 20∶3n−6 FA level in the case of the GLA diet suggest a reduction of prostaglandin
synthesis of the 2-series. The GLA diet also counteracted the increased level of 20∶4n−6 in PE by equalizing the nodule/surrounding
ratio. The low n−6/n−3 ratio diets significantly increased lipid peroxidation levels in hepatocyte nodules, mimicking the
level in the surrounding and control tissue while GSH was decreased. An increase in n−3 FA levels and oxidative status resulted
in a reduction in the number of glutathione-S-transferase positive foci in the liver of the GLA-fed rats. Modulation of cancer
development with low n−6/n−3 ratio diets containing specific dietary FA could be a promising tool in cancer intervention in
the liver. 相似文献
17.
F. Thies E. A. Miles G. Nebe-von-Caron J. R. Powell T. L. Hurst E. A. Newsholme P. C. Calder 《Lipids》2001,36(11):1183-1193
Greatly increasing the amounts of flaxseed oil [rich in α-linolenic acid (ALNA)] or fish oil (FO); [rich in eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease inflammatory cell functions and so might impair host defense.
The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, γ-linolenic
acid (GLA), arachidonic acid (ARA), DHA, or FO on inflammatory cell numbers and functions and on circulating levels of soluble
adhesion molecules. Healthy subjects aged 55 to 75 yr consumed nine capsules per day for 12 wk. The capsules contained placebo
oil (an 80∶20 mix of palm and sunflowerseed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA, or DHA or FO.
Subjects in these groups consumed 2 g ALNA; approximately 700 mg GLA, ARA, or DHA; or 1 g EPA plus DHA (720 mg EPA+280 mg
DHA) daily from the capsules. Total fat intake from the capsules was 4 g per day. None of the treatments affected inflammatory
cell numbers in the bloodstream; neutrophil and monocyte phagocytosis or respiratory burst in response to E. coli; production of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in response to bacterial lipopolysaccharide; or
plasma concentrations of soluble intercellular adhesion molecule-1. In contrast, the ALNA and FO treatments decreased the
plasma concentrations of soluble vascular cell adhesion molecule-1 (16 and 28% decrease, respectively) and soluble E-selectin
(23 and 17% decrease, respectively). It is concluded that, in contrast to previous reports using higher amounts of these fatty
acids, a moderate increase in consumption of long-chain n−6 or n−3 polyunsaturated fatty acids does not significantly affect
inflammatory cell numbers or neutrophil and monocyte responses in humans and so would not be expected to cause immune impairment.
Furthermore, we conclude that moderate levels of ALNA and FO, which could be incorporated into the diet, can decrease some
markers of endothelial activation and that this mechanism of action may contribute to the reported health benefits of n−3
fatty acids. 相似文献
18.
n−3 PUFA are well known for their anti-inflammatory effects. However, there has been only limited study on the kinetics of
incorporation and depletion of n−3 PUFA in immune cells. In the present study we investigated the incorporation and depletion
of n−3 PUFA in erythrocytes and leukocytes in mice during a 6-wk feeding period. Over the first 3-wk period (the incorporation
period) the mice were fed a special diet with a high n−3/n−6 PUFA ratio. In the following 3-wk period (the depletion period)
the mice were fed a standard chow diet. A linear incease of the concentration of EPA and DHA in erythrocyte membranes was
observed during the incorporation period, whereas a stagnation was observed after the second week for leukocytes. The level
of EPA did not fall to the background level after the depletion period, and the level of DHA was kept almost constant during
the depletion period in the erythrocyte membranes. In leukocytes the concentration of both EPA and DHA decreased during the
depletion period, but did not reach the background level after the 3-wk depletion. In conclusion, the kinetics of EPA and
DHA in the different cells are different. The rate of incorporation is faster than that of depletion for n−3 PUFA. More n−3
PUFA can be incorporated into leukocytes in comparison with erythrocytes. The ratio of n−3/n−6 PUFA is more important than
the amount of n−3 FA in changing the FA compositions of membrane lipids. 相似文献
19.
20.
Flaxseed, echium, and canola oils contain α-linolenic acid (18∶3n−3, ALA) in a range of concentrations. To examine their effect
on elevating cardiac levels of long-chain n−3 FA, diets based on these n−3-containing vegetable oils were fed to rats for
4 wk. Sunflower oil, which contains little ALA, was a comparator. Despite canola oil having the lowest ALA content of the
three n−3-containing vegetable oils, it was the most potent for elevating DHA (22∶6n−3) levels in rat hearts and plasma. However,
the relative potencies of the dietary oils for elevation of EPA (20∶5n−3) in heart and plasma followed the same rank order
as their ALA content, i.e., flaxseed>echium>canola>sunflower oil. This paradox may be explained by lower ALA intake leading
to decreased competition for Δ6 desaturase activity between ALA and the 24∶5n−3 FA precursor to DHA formation. 相似文献