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1.
Uptake and incorporation of long-chain fatty acids were studied in a human colorectal cancer cell line (HT29/219) grown in
culture medium supplemented with either fetal calf serum (FSC) or horse serum (HS). The cells were grown for 120 h with no
change of medium; the two major cellular lipid classes, the phospholipids and the triacylglycerols, were analyzed at regular
time-points. We observed significant changes in the concentration of most fatty acids throughout culture, and differences
in their composition when different sera were used to supplement the medium. Minimal levels of free fatty acids were found
in the cells, indicating a very small “free fatty acid pool”. A major difference between the cells grown in media supplemented
with different sera was the changes observed in concentrations of cellular polyunsaturated fatty acids during growth. In cells
grown with FCS (in which 20∶4n−6 is present), the levels of this acid in the phsopholipid and triacylglycerol fractions declined
rapidly during cell growth, suggesting further metabolism. In cells grown in medium supplemented with HS, 18∶2n−6 was the
major polyunsaturated acid present. There was clear evidence that this acid accumulated in the cellular triacylglycerol and
phospholipid fractions. Furthermore, its concentration did not decline during growth in culture, suggesting minimal conversion
to other polyunsaturated n−6 acids. Our results suggest that fatty acids from additional sources in the medium, for example
triacylglycerols and phospholipids associated with the lipoproteins, are taken up by the cells. There is also indication of
cellular fatty acid synthesis, particularly of monounsaturated and saturated acids during the culture period. HT29/219 cells
were shown to take up and incorporate radioactivity when trace amounts of [1-14C]-labeled arachidonic, linoleic or oleic acids were added to the culture medium. Most (80%) of the label was detected in
cellular phospholipids and triacylglycerols, although the specific activities of these various fatty acids were different
in the two lipid fractions. 相似文献
2.
An essential fatty acid (EFA) deficiency-like profile of fatty acids has been observed in HF-1 human skin fibro-blasts cultured
at clonal densities in MCDB 110 and 0.4% fetal bovine serum (FBS). The profile was characterized by an accumulation of 16∶1n−7,
18∶1n−9, 20∶3n−9 and 22∶3n−9, a reduction of n−6 fatty acids and a reduction in total polyunsaturated fatty acids (PUFA).
The fatty acid composition of sphingomyelin (SPH), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol
(PI) and phosphatidylethanolamine (PE) was determined and, except for SPH, each displayed an EFA deficiency-like profile.
The triene to tetraene ratio (20∶3n−9/20∶4n−6) ranged from 5.3 in PI to 0.9 in PE. In addition, the highest percentage of
20∶3n−9 was present in the PI and the highest percentage of 22∶3n−9, in PE. Other human fibroblasts (normal, transformed and
at different population doubling number levels [PDL] were grown under the same conditions and were found to display triene
to tetraene ratios (20∶3n−9/20∶4n−6) in total cellular lipids ranging from 0.7 to 4.5. The accumulation of 20∶3n−9 and 22∶3n−9
is due primarily to the existence of a basal nutrient medium (MCDB 110) that allows for the rapid clonal growth of human fibroblasts
at reduced serum levels (0.4%). This culture procedure can be exploited to further elucidate various aspects of lipid metabolism
in human fibroblasts.
Fatty acids are abbreviated as number of carbon atoms: number of double bonds, followed by an n-number to designate the position
of the first double bond with respect to the methyl carbon. Thus, Mead acid is 20∶3n−9 and its elongation product is 22∶3n−9. 相似文献
3.
This study has utilized radiolabeled analogues of arachidonic acid to study the substrate specificity of elongation of long-chain
polyunsaturated fatty acids. Human umbilical vein endothelial cells were incubated for 2–72 hr in medium supplemented with
0.9–2.6 μM [14C]fatty acid, and cellular glycerolipids were analyzed by gas-liquid chromatography with radioactivity detection. Elongation
of naturally occurring C20 polyunsaturated fatty acids occurred with eicosapentaenoate (20∶5(n−3))>Mead acid (20∶3(n−9))>arachidonate (20∶4(n−6)). Chain
length markedly influenced the extent of elongation of 5,8,11,14-tetraenoates (18∶4>19∶4>20∶4>21∶4); effects of initial double
bond position were also observed (6,9,12,15–20∶4>4,7,10,13–20∶4. Neither 5,8,14- nor 5,11,14–20∶3 was elongated to the extent
of 5,8,11–20∶3. Differences between polyunsaturated fatty acids were observed both in the initial rates and in the maximal
percentages of elongation, suggesting that the content of cellular C20 and C22 fatty acids may represent a balance between chain elongation and retroconversion.
Umbilical vein endothelial cells do not exhibit significant desaturation of either 22∶4(n−6) or 22∶5(n−3). By contrast, incubation
with 5,8,11,14-[14C]18∶4(n−4) resulted in formation of both [14C]20∶5(n−4) and [14C]22∶5(n−4). The respective time courses for the appearances of [14C]22∶5(n−4) and [14C]20∶5(n−5) suggests Δ6 desaturation of [14C]22∶4(n−4) rather than Δ4 desaturation of [14C]20∶4(n−4). 相似文献
4.
Ikuo Ikeda Jun Murakami Takayuki Oka Michihiro Sugano Hideaki Yamada Sakayu Shimizu Hiroshi Kawashima Yoshifumi Shinmen Teruo Amachi 《Lipids》1991,26(1):27-30
The effects of perfused oleic (18∶1n−9), arachidonic (20∶4n−6) and 5,8,11,14-nonadecatetraenoic (19∶4n−5) acids on triglyceride
and cholesterol secretion and ketone body production were studied in isolated rat liver. As compared to oleic and 19∶4n−5
acids, both ketone body production and triglyceride secretion were significantly lowered when arachidonic acid was perfused.
The concentration of triglyceride in the post-perfused liver was lower upon perfusion with arachidonic acid than upon perfusion
with oleic acid or 19∶4n−5 acid. Cholesterol secretion in the liver perfused with arachidonic acid or 19∶4n−5 acid was significantly
higher than with oleic acid. The concentration of cholesterol in the post-perfused liver was slightly but significantly higher
with 19∶4n−5 acid than with the other fatty acids. The results suggest that 19∶4n−5 acid when compared with arachidonic acid
affects lipid metabolism in liver differently. 相似文献
5.
The linoleic acid content of phosphatidylethanolamine (PE), phosphatidylcholine (PC) and triglyceride (TG) rapidly fell in
rat hepatocytes in primary culture up to four days and in coculture with liver epithelial cells up to eight days. At the same
time, the level of polyunsaturated fatty acids (PUFA), especially arachidonic acid, remained constant in PE, slightly decreased
in PC and dropped in TG. There was no variation of the nonessential PUFA, 20∶3n−9.
Linoleic acid supplementation of cultures 24 hr before the harvest induced a rise in the linoleic acid level of the three
lipid classes. Arachidonic acid remained constant in TG and only slightly decreased in PE and PC at day 4 of primary culture
and day 8 of coculture. The level of 20∶3n−9 increased in PE and PC and much more in TG. This net increase in the arachidonic
acid and 20∶3n−9 levels in TG could not be explained only by a transfer from the phospholipid pools of PUFA because the phospholipid
content of hepatocytes and PUFA levels of phospholipids did not vary under linoleic supplementation. The low percentage of
arachidonic acid in epithelial cells rules out any participation of these cells in the increase of arachidonic acid in supplemented
cocultures.
Triglycerides may act as a storage pool for plasma PUFA up to four days of primary culture and eight days of coculture. Besides,
coculture seems more potent than primary culture to maintain the phospholipid level, to spare the essential PUFA in PE and
to increase the TG synthesis in response to linoleic acid supplementation. 相似文献
6.
The purpose of this study was to determine the effects of dietary fat quantity and fatty acid composition on hepatic H2O2-metabolizing systems, activities of NADPH-generating enzymes and lipid peroxidation. Onemonth-old male C57BL/6J mice were
fed one of six diets: (i) 5% fat, rich in 18∶2n−6 fatty acid (5% N−6); (ii) 20% fat, rich in 18∶3n−3 (N−3); (iii) 20% fat,
rich in 18∶2n−6 (N−6); (iv) 20% fat, rich in 18∶1n−9 (N−9); (v) 20% fat, rich in saturated fatty acids (SAT); and (vi) 20%
fat, deficient in essential fatty acids (EFAD); for 11 wk. Comparisons between animal groups receiving different fat quantities
showed that activities of glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) and malic enzyme (ME, EC 1.1.1.40) and the
levels of conjugated dienes were significantly lower in the N−6 than in 5% N−6 group. Conversely, activities of catalase (CAT,
EC 1.11.1.6) and seleniumglutathione peroxidase (SeGSHPx, EC 1.11.1.9) were higher in the N−6 than in 5% N−6 group. Among
the five dietary groups receiving 20% fat but differing in fatty acid composition, CAT activity was lower in the N−9 group,
SeGSHPx activity was lower in the EFAD group, and glutathione reductase (GSSGR, EC 1.6.4.2) activity was higher in the N−6
than in the N−3, N−9, SAT and EFAD groups. The EFAD group had much higher levels of total lipids and conjugated dienes, as
well as activities of NADPH-generating enzymes, including G6PDH, ME and isocitrate dehydrogenase (EC 1.1.1.42), than the other
four high-fat groups. The hepatic levels of malondialdehyde were not different among the five groups fed 20% fat. In the EFAD
group, higher hepatic lipid content can be attributed to higher activities of NADPH-generating enzymes, and the elevation
of conjugated diene levels may be related to increased oxygenation of 20∶−6 (Mead acid)via the lipoxygenase/cyclooxygenase pathway. In short, both dietary fat quantity and fatty acid composition selectively affected
hepatic H2O2-metabolizing systems, activities of NADPH-generating enzymes and lipid peroxidation status. 相似文献
7.
Ghafoorunissa 《Lipids》1990,25(11):763-766
Cereals and pulses alone provide nearly two-thirds of the daily linoleic acid requirement in habitual Indian diets. Two-thirds
of the lipids present in cereals is in bound form. To investigate to what extent the essential fatty acids (EFA) present in
cereals and pulses are biologically available, weanling rats were fed rice-pulse based diets either without supplementation
or supplemented with one of three vegetable oils—coconut, palmolein or groundnut oil. Plasma phospholipid fatty acid composition
was used to assess the EFA status, with ratios of eicosatrienoic/arachidonic acids (20∶3n−9/20∶4n−6) above 0.2, indicating
linoleic acid deficiency. In the unsupplemented group, the levels of linoleic and arachidonic acids were low as compared to
the groundnut oil fed group. However, the ratio of 20∶3n−9/20∶4n−6 was less than 0.2, indicating that there was no linoleic
acid deficiency. This shows that the linoleic acid present in rice and pulse may be readily available. 相似文献
8.
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
9.
The aim of this study was to investigate the effect of the oxysterol 5α-cholestane-3β, 5, 6β-triol (triol) on the metabolism
of linoleic acid (18∶2n−6) to arachidonic acid (20∶4n−6) and on the cell membrane fatty acid composition. Porcine kidney cells
were incubated in medium with or without 10 μg/mL of triol for 24 h, then incubated for 1, 6, or 12 h in a medium which contained
50 μM of either [14C]linoleic acid or unlabeled linoleic acid. The cellular uptake of [14C] linoleic acid was significantly higher in the triol-treated cells than in control cells. After 1- and 6-h incubations despite
the increase of [14C]linoleic acid pool size in the triol-treated cells, neither total n−6 polyunsaturated fatty acids (PUFA) metabolites nor
arachidonic acid were increased in the triol-treated cells as compared to the control cells, but trienoic acids accumulated
to a greater extent in the triol-treated cells. Therefore, the ratios of n−6 PUFA metabolites vs. pool size of linoleic acid
and of tetraenoic acids vs. dienoic acids were significantly decreased in triol-treated cells as compared to the control cells.
The cellular fatty acid composition also showed that linoleic acid percentage was significantly increased while arachidonic
acid percentage was significantly decreased in the triol-treated cells, and that the accumulation of trienoic acids (18∶3n−6+20∶3n−6)
observed from the [14C]linoleic acid experiment was due solely to increased 20∶3n−6 content. This latter finding indicates that a decrease of elongase
activity by triol is unlikely. Our results also showed that the triol-treated cells had a lower level of free cholesterol
but higher levels of phospholipid and triol in their membranes, suggesting that triol displaced free cholesterol from the
cell membrane. 相似文献
10.
The influence of age and cholesterol on polyunsaturated fatty acids (PUFa) levels was studied in young and old male Sprague-Dawley
rats. Animals were fed a fat-free diet supplemented with 10% (by wt) safflower oil with or without 1% cholesterol for 8 wk.
As a result of cholesterol feeding, proportions of linoleic acid (18∶2n−6) and dihomo-γ-linolenic acid (30∶3n−6) were increased
and and that of arachidonic acid (20∶4n−6) was decreased in the liver and platelet phospholipids in 64-wk-old rats, suggesting
inhibitory effects of cholesterol on 20∶4n−6 synthesis from 18∶2n−6. The prominent age-dependent effect on the levels of PUFA
was a retention of C−22 n−3 PUFA, accompanied by decreased C−22 n−6 PUFA and increased 20∶3n−6 in the liver and platelet phospholipids.
Ratio of 20∶3n−6/20∶4n−6 increased in 64-wk-old rats regardless of dietary cholesterol, suggesting depressed Δ5-desaturase
with age. In aorta phospholipids, 20∶3n−6 content and 20∶3n−6/20∶4n−6 ratio increased with cholesterol supplementation, but
not with age. These results suggest that changes of PUFA composition of platelet phospholipids with age are closely linked
with changes in liver phospholipids. The 20∶4n−6 content in both platelet and aorta phospholipids is kept constant, despite
other n−6 and n−3 PUFA being affected by age. 相似文献
11.
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
12.
The effect of stearidonic acid (18∶4n−3) present in fish and some plant oils, such as black currant seed oil, was studied
on human platelets. When added to platelets simultaneously with collagen, arachidonic acid or endoperoxide mimetic U46619,
18∶4n−3 appeared as a weak inhibitor of platelet aggregation. In addition, 18∶4n−3 did not alter the metabolism of exogenous
arachidonic acid. In contrast, when preincubated with platelets after precoating onto albumin, 18∶4n−3 inhibited platelet
aggregation induced by thrombin, collagen, arachidonic acid or U46619, and was as potent as eicosapentaenoic acid (20∶5n−3)
tested under similar conditions. Stearidonic acid also altered the endogenous arachidonate oxygenation stimulated by low doses
of thrombin, but to a significantly lesser extent than did 20∶5n−3. It seems therefore that, in addition to competing with
endogenous arachidonate metabolism, 18∶4n−3 may affect platelet aggregation by another mechanism. 相似文献
13.
The fate of labeled linoleic, α-linolenic, and higher homologs of α-linolenic acid administered to the yellow clam,Mesodesma mactroides, was investigated. It was found that the clam incorporated the acids dissolved in sea water and converted 18∶2 (n−6) into
20∶2 (n−6) and 18∶3 (n−3) into 18∶4 (n−3) and 20∶3 (n−3). The addition of casein hydrolysate to the sea water increased the
desaturation capacity of the clam and allowed the conversion of 18∶2 (n−6) into 18∶3 (n−6) to be demonstrated. An enhanced
desaturation of 18∶3 (n−3) into 18∶4 (n−3) was also demonstrated. After 12 hr administration of the acid, no radioactivity
was found in arachidonic, 20∶5 (n−3), or 22∶6 (n−3). Feeding the clams a culture ofPhaeodactylum tricornutum previously incubated with 1-14C-α-linolenic acid demonstrated that all the homologs of the α-linolenic series were found in the clam without any important
changes. Six hour administration of labeled linolenic acid resulted in the incorporation of the acid into diglycerides and
phospholipids.
Member of the carrera del Investigador Cientifico of the Consejo Nacional de Investigaciones Cientificas y Tecnicas 相似文献
14.
The extent to which exogenous 18∶3(n−3) and 18∶3(n−6) were desaturated and elongated and the degree to which they and their
derivatives altered the unsaturation index of cell glycerolipids were compared using clone 4 MDCK cells grown in lipid- and
serum-free medium. Despite differences in the degree of unsaturation of the individual polyunsaturated fatty acids produced
from 18∶3(n−3) or 18∶3(n−6), the unsaturation index of phospholipids increased similarly from 0.7 in control cells grown in
serum- and lipid-free medium to ca. 1.6 in those supplemented with fatty acid. The added fatty acids had little effect on
cell growth. The conversion of 18∶3(n−6) to 20∶3(n−6) and 20∶4(n−6) was more rapid than that of 18∶3(n−3) to 20∶4(n−3) and
20∶5(n−3). No significant quantities of 20∶3(n−3) or 18∶4(n−3) were noted. When both 18∶3 isomers were supplied simultaneously,
marked differences in the amounts of some species of n−3 and n−6 polyunsaturated fatty acids were observed. The presence of
18∶3(n−6) and/or its derivatives suppressed levels of 20∶4(n−3) and 20∶5(n−3), perhaps through inhibition of the Δ6 and Δ5
desaturases responsible for their synthesis from 18∶3(n−3). Similarly 18∶3(n−3), and/or its longer more unsaturated derivatives,
diminished the formation of 20∶4(n−6) from 18∶3(n−6). No marked effect on the products derived from elongation alone were
observed. 相似文献
15.
The purpose of this study was to examine the influence of long-term feeding of dietary fat rich in either n−3 or n−6 fatty
acids on the availability of arachidonic acid (20∶4n−6) in major phospholipids of gastric mucosa in rats. Three groups of
male Wistar rats were fed either a standard diet, a cod liver oil-enriched diet (10% by weight), or a corn oil-enriched diet
(10% by weight) for 8 mon. Dietary cod liver oil significantly reduced the level of 20∶4n−6 in phosphatidylcholine (PC) and
in phosphatidylethanolamine (PE) of gastric mucosa. The loss of 20∶4n−6 was compensated for by eicosapentaenoic acid (20∶5n−3)
in PC, whereas the decrease in 20∶4n−6 in PE corresponded to the increase in three n−3 fatty acids: 20∶5n−3, docosapentaenoic
acid (22∶5n−3), and docosahexaenoic acid (22∶6n−3). The level of 20∶5n−3 was higher than the level of 22∶6n−3 both in PC and
PE of mucosa in rats fed cod liver oil. Diets supplemented with corn oil increased the level of 18∶2n−6 but decreased the
monoene fatty acids 16∶1 and 18∶1n−7 in PC but not in PE of gastric mucosa. The 20∶4n−6 levels of both PC and PE were markedly
reduced by dietary cod liver oil, to about one-third of control levels. Similar changes were also observed in the stomach
wall. Gastric erosions were observed in all rats exposed to restriction stress, but this form of stress induced twice the
number of erosions in rats fed fish oil compared to control rats or rats fed corn oil. We conclude that a diet rich in fish
oil altered the balance between n−6 and n−3 fatty acids in major gastric mucosal phospholipids, markedly reduced the availability
of 20∶4n−6, and increased the incidence of gastric erosions induced by restriction or emotional stress. 相似文献
16.
In this investigation, we demonstrate that rat liver epithelial (WB-F344) cells grown in medium supplemented with n−3 fatty
acids (FA) results in the inhibition of gap junctional intercellular communication (GJIC). Cells incubated for 48 hr in medium
containing 50 μM α-linolenate (18∶3n−3) resulted in a 60% inhibition of GJIC, compared to control cells, while treatment with
γ-linolenate (18∶3n−6) had no effect. Supplementation with octadecatetraenoate (18∶4n−3), eicosapentaenoate (20∶5n−3), and
docosahexaenoate (22∶6n−3), inhibited GJIC by 42%, 28%, and 18%, respectively. Incubation with each of the n−3 FA markedly
increased the total n−3 FA content of cellular phospholipids (PL). Growing cells in medium containing 50 μM arachidonate (20∶4n−6)
plus 50 μM 18∶3n−3 partially attenuated the inhibition of GJIC induced by 18∶3n−3. The mechanism by which n−3 FA inhibit GJIC
remains to be determined. 相似文献
17.
Δ5 Desaturation of eicosa-8,11,14-trienoic acid to arachidonic acid was studied in rat liver microsomes. It was shown that
Δ5 desaturation of fatty acids in vitro requires the participation of a peripheral component of cytosolic origin. Desaturation
of 20∶3n−6 to 20∶4n−6 decreases in washed microsomes as they lose an adsorbed cytosolic fraction (CF), but the enzymatic activity
can be recovered as a function of CF concentration in the incubation medium. Albumin does not substitute for CF. Δ5 Desaturation
of 20∶3n−6 is inhibited by arachidonic acid by a product inhibition effect, but CF prevents retroinhibition of Δ5-desaturase
by 20∶4n−6. This ability of CF is eliminated by preincubation of CF with 20∶4n−6, but not with γ−18∶3n−6, the product of Δ6
desaturation of 18∶2n−6, thus indicating that CF impairs the retroinhibitory effect of arachidonic acid on Δ5-desaturase in
a specific manner. Δ6 Desaturation of linoleic acid to γ−18∶3n−6 is also activated by CF and retroinhibited by γ−18∶3n−6.
CF activity on Δ6 desaturation is retained after preincubation with 20∶4n−6, but it is lost after preincubation with γ−18∶3n−6.
Activation of Δ6-desaturase by CF is associated with the removal of the reaction product in a specific manner. Chromatography
of CF by Sephacryl S-200 separates two major subfractions which show different efficiency in reactivating Δ5- and Δ6-desaturase
activities in washed microsomes. Therefore, CF may contain subfractions that can prevent Δ5- and δ6-desaturase retroinhibition
by apparently binding their respective reaction products specifically. 相似文献
18.
Guinea pigs were fed one of three diets containing 10% black currant seed oil (a source of gamma-linolenic (18∶3 n−6) and
stearidonic (18∶4 n−3) acids), walnut oil or lard for 40 days. The fatty acid composition of liver triglycerides, free fatty
acids, cholesteryl esters, phosphatidylinositol, phosphatidylserine, cardiolipin, phosphatidylcholine and phosphatidylethanolamine
were determined.
Dietary n−3 fatty acids found esterified in liver lipids had been desaturated and elongated to longer chain analogues, notably
docosapentaenoic acid (22∶5 n−3) and docosahexaenoic acid (22∶6 n−3). When the diet contained low amounts of n−6 fatty acids,
proportionately more of the n−3 fatty acids were transformed. Significantly more eicosapentaenoic acid (EPA) (20∶5 n−3) was
incorporated into triglycerides, cholesteryl esters, phosphatidylcholine and phosphatidylethanolamine of the black currant
seed oil group compared with the walnut oil group.
Feeding black currant seed oil resulted in significant increases of dihomogamma-linolenic acid (20∶3 n−6) in all liver lipid
classes examined, whereas the levels of arachidonic acid (20∶4 n−6) remained relatively stable. The ratio dihomo-gamma-linolenic
acid/arachidonic acid was significantly (2.5-fold in PI to 17-fold in cholesteryl esters) higher in all lipid classes from
the black currant seed oil fed group. 相似文献
19.
Docosahexaenoic acid (DHA, 22∶6n−3) is an n−3 polyunsaturated fatty acid which attenuates the development of hypertension
in spontaneously hypertensive rats (SHR). The effects of DHA on delta-9-desaturase activity in hepatic microsomes and fatty
acid composition were examined in young SHR. Two groups of SHR were fed either a DHA-enriched diet or a control diet for 6
wk. Desaturase activity and fatty acid composition were determined in hepatic microsomes following the dietary treatments.
Delta-9-desaturase activity was decreased by 53% in DHA-fed SHR and was accompanied by an increase in 16∶0 and a reduction
in 16∶1n−7 content in hepatic microsomes. The DHA diet also increased the levels of eicosapentaenoic acid (20∶5n−3) and DHA.
The n−6 fatty acid content was also affected in DHA-fed SHR as reflected by a decrease in gamma-linolenic acid (18∶3n−6),
arachidonic acid (20∶5n−6), adrenic acid (22∶4n−6), and docosapentaenoic acid (22∶5n−6). A higher proportion of dihomo-gamma-linolenic
acid (20∶3n−6) and a lower proportion of 20∶4n−6 is indicative of impaired delta-5-desaturase activity. The alterations in
fatty acid composition and metabolism may contribute to the antihypertensive effect of DHA previously reported. 相似文献
20.
Michel Guichardant Helmut Traitler Danièle Spielmann Howard Sprecher Paul-André Finot 《Lipids》1993,28(4):321-324
Leukotrienes have been shown to play an important role as mediators in various disease processes, including asthma and inflammation;
thus, their synthesis is tightly regulated. The major precursor of leukotrienes is arachidonic acid (20∶4n−6). Fatty acids
which are structurally similar to 20∶4n−6, such as eicosatrienoic acid (20∶3n−6; dihomogammalinolenic acid) and eicosapentaenoic
acid (20∶5n−3; timnodonic acid) have been found to inhibit leukotriene biosynthesis. Because of the structural similarity
of octadecatetraenoic acid (18∶4n−3; stearidonic acid) with 20∶4n−6, the present study was undertaken to determine whether
stearidonic acid also exerts an inhibitory effect on the 5-lipoxygenase pathway. Human leukocytes were incubated with 18∶4n−3
(20 μM or 10 μM), 20∶5n−3 (20 μM) or 20∶3n−6 (20 μM) and subsequently stimulated with 1 μM ionophore A23187 and 20∶4n−6 (20
μM or 10 μM). The 5-lipoxygenase products were then measured by high-performance liquid chromatography. Leukotriene synthesis
was reduced by 50% with 20 μM 18∶4n−3 and by 35% with 10 μM 18∶4n−3. Formation of 5S,12S-di-hydroxy-eicosatetraenoic acid and of 5-hydroxy-eicosatetraenoic acid was decreased by 25% with 20 μM 18∶4n−3 and by 3%
with 10 μM 18∶4n−3. The inhibition observed with 20 μM 18∶4n−3 appeared to be of the same order as that observed with 20 μM
20∶5n−3; the inhibition observed with 18∶4n−3 was shown to be dosedependent. The inhibition produced by 20 μM 20∶3n−6 was
greater than that observed with either 20 μM 18∶4n−3 or with 20 μM 20∶5n−3. The results suggest that stearidonic acid, which
is found, for example, in blackcurrant seed oil (which also contains the 20∶3n−6 precursor), may play a role in suppressing
inflammation. 相似文献