Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A:1,2-diacylglycerol acyltransferase

The mechanism for the reduced hepatic production of triacylglycerol in the presence of eicosapentaenoic acid was explored in short-term experiments using cultured parenchymal cells and microsomes from rat liver. Oleic, palmitic, stearic, and linoleic acids were the most potent stimulators of triacyl[3H]glycerol synthesis and secretion by hepatocytes, whereas erucic, alpha-linolenic, gamma-linolenic, arachidonic, docosahexaenoic, and eicosapentaenoic acids (in decreasing order) were less stimulatory. There was a linear correlation (r = 0.85, P less than 0.01) between synthesis and secretion of triacyl[3H]glycerol for the fatty acids examined. The extreme and opposite effects of eicosapentaenoic and oleic acids on triacylglycerol metabolism were studied in more detail. With increasing number of free fatty acid molecules bound per molecule of albumin, the rate of synthesis and secretion of triacyl[3H]glycerol increased, most markedly for oleic acid. Cellular uptake of the two fatty acids was similar, but more free eicosapentaenoic acid accumulated intracellularly. Eicosapentaenoic acid caused higher incorporation of [3H]water into phospholipid and lower incorporation into triacylglycerol and cholesteryl ester as compared to oleic acid. No difference was observed between the fatty acids on incorporation into cellular free fatty acids, monoacylglycerol and diacylglycerol. The amount of some 16- and 18-carbon fatty acids in triacylglycerol was significantly higher in the presence of oleic acid compared with eicosapentaenoic acid. Rat liver microsomes in the presence of added 1,2-dioleoyl-glycerol incorporated eicosapentaenoic acid and eicosapentaenoyl-CoA into triacylglycerol to a lesser extent than oleic acid and its CoA derivative. Decreased formation of triacylglycerol was also observed when eicosapentaenoyl-CoA was given together with oleoyl-CoA, whereas palmitoyl-CoA, stearoyl-CoA, linoleoyl-CoA, linolenoyl-CoA, and arachi-donoyl-CoA had no inhibitory effect. In conclusion, inhibition of acyl-CoA:1,2-diacylglycerol O-acyltransferase (EC 2.3.1.20) by eicosapentaenoic acid may be important for reduced synthesis and secretion of triacylglycerol from the liver.     

The metabolism of 8-heptadecene in Pyropia (Bangiaceae,Rhodophyta)

The metabolic pathway of 8-heptadecene in red algae was investigated. The results showed that the amounts of 8-heptadecene in the primitive bangiophycidean red algae Pyropia and Bangia were 30–50 % of the volatile compounds, much higher than that in the green alga Ulva pertusa, the brown alga Sargassum thunbergii and the florideophycidean red alga Gracilaria lemaneiformis. Studies on the metabolism of 8-heptadecene in Pyropia found that its enzymatic system has no significant catalytic activity on palmitic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid. However, the isolated enzymatic solution showed activity in the presence of eicosapentaenoic acid. This activity produced about four times the amount of 8-heptadecene compared with other substrates and the control, indicating the solution had a specific catalytic function for eicosapentaenoic acid. Furthermore, the enzyme solution was strongly inhibited by NaN₃ but not by phenidone and phenanthroline suggesting that the enzyme is structurally related to heme protein. Thus, it is believed that a constant amount of 8-heptadecene is maintained in the primitive red alga Pyropia and the 8-heptadecene is a metabolite of eicosapentaenoic acid and may catalyzed by enzymes including a heme lipoxygenase-like enzyme.     

Differential effects of eicosapentaenoic acid and oleic acid on lipid synthesis and secretion by HepG2 cells

The effects of eicosapentaenoic acid and oleic acid on lipid synthesis and secretion by HepG2 cells were examined to identify fatty acid specific changes in lipid metabolism that might indicate a basis for the hypolipidemic effect attributed to eicosapentaenoic acid and related n-3 fatty acids. Cellular glycerolipid synthesis, as determined by [3H]glycerol incorporation, increased in a concentration-dependent manner in cells incubated 4 h with either eicosapentaenoic acid or oleic acid at concentrations between 10 and 300 microM. [3H]Glycerol-labeled triglyceride was the principal lipid formed and increased approximately fourfold with the addition of 300 microM oleic acid or eicosapentaenoic acid. Both fatty acids also produced a 20-40% increase in the total cellular triglyceride mass. Although both fatty acids increased triglyceride synthesis to similar extents, eicosapentaenoic acid-treated cells secreted 40% less [3H]glycerol-labeled triglyceride than cells fed oleic acid. Cellular synthesis of [3H]glycerol-labeled phosphatidylethanolamine and phosphatidylcholine was also reduced by 40% and 30%, respectively, in cells given eicosapentaenoic acid versus cells given oleic acid. Similar results were obtained in determinations of radiolabeled oleic acid and eicosapentaenoic acid incorporation. At a fatty acid concentration of 300 microM, incorporation of radiolabeled eicosapentaenoic acid into cellular triglycerides was greater than the incorporation obtained with radiolabeled oleic acid, while the reverse relationship was observed for the formation of phosphatidylcholine from the same fatty acids. Eicosapentaenoic acid is as potent as oleic acid in inducing triglyceride synthesis but eicosapentaenoic acid is a poorer substrate than oleic acid for phospholipid synthesis. The intracellular rise in de novo-synthesized triglyceride in eicosapentaenoic acid-treated cells without corresponding increases in triglyceride secretion suggests that eicosapentaenoic acid is less effective than oleic acid in promoting the transfer of de novo-synthesized triglyceride to nascent very low density lipoproteins.     

Occurrence of conjugated polyenoic fatty acids in seaweeds from the Indian Ocean

Three species of red marine macro algae (Rhodophyta) from the Indian Ocean were analysed for the occurrence of conjugated polyenes. The composition of different lipid classes in these seaweeds along with their fatty acid composition has also been reported. Analysis of lipid classes of these seaweeds revealed that both Acanthophora spicifera (Ceramiales, Rhodophyta) and two species of Gracilaria, viz. G. edulis and G. folifera (Gracilariales, Rhodophyta) were rich in glycolipids followed by neutral- and phospholipids. The fatty acid composition of these seaweeds revealed C16:0 as the predominant fatty acid in all three species. However, A. spicifera had significantly higher amounts of eicosapentaenoic acid (EPA) and arachidonic acid (AA) as compared to negligible amount of these fatty acids in both species of Gracilaria. The red seaweed Acanthophora spicifera contained conjugated eicosapentaenoic acid (CEPA) and conjugated arachidonic acid (CAA) in all lipid classes except glycolipids.     

Effect of eicosapentaenoic acid on triacylglycerol transport in CaCo-2 cells

The human intestinal cell line, CaCo-2, was used to study the effect of the n-3 fatty acid, eicosapentaenoic acid, on triacylglycerol secretion. In cells incubated with 250 microM eicosapentaenoic acid, the incorporation of [3H]glycerol into triacylglycerols secreted into the medium was decreased by 58% compared to cells incubated with 250 microM oleic acid. The incorporation of [3H]glycerol into cellular triacylglycerols was decreased 32% in cells incubated with eicosapentaenoic acid. In cells preincubated with [3H]glycerol to label existing triacylglycerols, the rates of secretion of preformed triacylglycerols were similar in response to the addition of either fatty acid. Initial uptake rates of the n-3 fatty acid were higher than for oleic acid. Both eicosapentaenoic acid and oleic acid were minimally oxidized to CO2. Oleic acid was predominantly incorporated into cellular triacylglycerols (62% vs. 47%), whereas more eicosapentaenoic acid was incorporated into cellular phospholipids (46% vs. 30%). Phospholipids of microsomes prepared from cells incubated with eicosapentaenoic acid were enriched in this fatty acid. The rate of synthesis of triacylglycerol and diacylglycerol acyltransferase activities were significantly less in microsomes prepared from cells incubated with eicosapentaenoic acid. Triacylglycerol mass secreted by CaCo-2 cells incubated with either fatty acid was similar. In CaCo-2 cells, eicosapentaenoic acid decreases the synthesis and secretion of newly synthesized triacylglycerol without decreasing the secretion of triacylglycerol mass. Modification of microsomal membrane phospholipid fatty acid composition is associated with a decrease in microsomal triacylglycerol synthesis and diacylglycerol acyltransferase activities.     

Eicosapentaenoic acid inhibits cholesterol esterification in cultured parenchymal cells and isolated microsomes from rat liver

The effects of eicosapentaenoic acid on synthesis and secretion of cholesterol and cholesterol ester by cultured rat hepatocytes were studied. In the presence of eicosapentaenoic acid cellular cholesterol esterification was decreased by 50-75% compared to oleic acid as measured by radioactive precursors and mass. Secretion of cholesterol ester was reduced by 50-60% in the presence of eicosapentaenoic acid as evaluated by radiolabeled fatty acids, mevalonolactone, and mass measurement. Oleic, palmitic, and stearic acid increased, whereas eicosapentaenoic and docosahexaenoic acid decreased synthesis and secretion of cholesterol ester as compared to a fatty acid-free control. Cellular and secreted free cholesterol were unaffected by eicosapentaenoic acid in comparison with oleic acid. The reduced cholesterol esterification was observed within 1 h and lasted for at least 20 h. Eicosapentaenoic acid caused lower cholesterol esterification than oleic acid in the concentration range 0.2-1.0 mM fatty acid and reduced the stimulatory effect of oleic acid on cholesterol ester formation. Cholesterol esterification and release of cholesterol ester were markedly increased by 25-hydroxycholesterol in the presence of eicosapentaenoic acid as well as oleic acid. Experiments with liver microsomes revealed that radioactive eicosapentaenoic acid and eicosapentaenoyl-CoA were poorer substrates (7-30%) for cholesterol esterification than oleic acid and oleoyl-CoA. Reduced formation of cholesterol ester was also observed when eicosapentaenoyl-CoA was given together with labeled oleoyl-CoA, whereas palmitoyl-CoA, stearoyl-CoA, linolenoyl-CoA, and arachidonoyl-CoA had no inhibitory effect. In conclusion, eicosapentaenoic acid reduced cellular cholesterol esterification by inhibiting the activity of acyl-CoA:cholesterol acyltransferase. The lowered cholesterol esterification caused by eicosapentaenoic acid secondly decreased secretion of very low density lipoprotein cholesterol ester.     

Synthesis and metabolism of arachidonyl- and eicosapentaenoyl-CoA in rat aorta

In studies on the metabolism of polyunsaturated fatty acids, acyl-CoA synthetase for 5,8,11,14-20:4 (arachidonic acid) and 5,8,11,14,17-20:5 (eicosapentaenoic acid) and the incorporation of these fatty acids into complex lipids and their conversion to CO2 were investigated in rat aorta. The activity of acyl-CoA synthetase was 35.9 for arachidonic acid and 63.0 for eicosapentaenoic acid (nmol/mg protein per 10 min) and the apparent Km values were 45 microM for arachidonic acid and 56 microM for eicosapentaenoic acid. Inhibition of eicosapentaenoyl-CoA synthesis by arachidonic acid was stronger than that of arachidonyl-CoA synthesis by eicosapentaenoic acid. Arachidonic acid and eicosapentaenoic acid were mostly incorporated into phospholipids. The incorporation of these fatty acids into cholesterol ester and their conversion to CO2 were less than those of palmitic acid, but their incorporation into triacyglycerol was greater. The incorporation of these fatty acids into phosphatidylserine + phosphatidylinositol and phosphatidylethanolamine was also greater than that of palmitic acid. The patterns of incorporation of arachidonic acid and eicosapentaenoic acid were similar. The physiological roles of these polyunsaturated fatty acids and the interference of eicosapentaenoic acid in arachidonic acid metabolism are discussed on the basis of these results.     

Eicosapentaenoic acid inhibits synthesis and secretion of triacylglycerols by cultured rat hepatocytes

Primary cultures of rat hepatocytes were used to study the effects of eicosapentaenoic and oleic acid on synthesis and secretion of triacylglycerols associated with very low density lipoproteins. From the experiments the following was observed. Oleic acid markedly stimulates secretion as well as synthesis of triacylglycerols, whereas eicosapentaenoic acid causes very little or no increase in secretion or synthesis as compared to a fatty-acid-free medium. The effects could already be observed after 15 min incubation. The inhibitory effect of eicosapentaenoic acid is reversible within 1-2 h. Eicosapentaenoic acid inhibits much of the stimulatory effect of oleic acid on synthesis and secretion of triacylglycerols. The cellular uptake of eicosapentaenoic acid is somewhat higher than that of oleic acid and the metabolism of these fatty acids to acid-soluble materials is similar. Eicosapentaenoic acid does not affect the secretory pathway of triacylglycerols per se. From these results it may be concluded that the mechanism for the inhibitory effect of eicosapentaenoic acid on triacylglycerol secretion is probably via reduced triacylglycerol synthesis.     

Eicosapentaenoic acid utilization by bovine aortic endothelial cells: effects on prostacyclin production

We have investigated whether the presence of other fatty acids in physiologic amounts will influence the effects of eicosapentaenoic acid on cellular lipid metabolism and prostaglandin production. Eicosapentaenoic acid uptake by cultured bovine aortic endothelial cells was time and concentration dependent. At concentrations between 1 and 25 microM, most of the eicosapentaenoic acid was incorporated into phospholipids and of this, 60-90% was present in choline phosphoglycerides. Eicosapentaenoic acid inhibited arachidonic acid uptake and conversion to prostacyclin (prostaglandin I2) but was not itself converted to eicosanoids. Only small effects on the uptake of 10 microM eicosapentaenoic acid occurred when palmitic, stearic or oleic acids were added to the medium in concentrations up to 75 microM. In contrast, eicosapentaenoic acid uptake was reduced considerably by the presence of linoleic, n-6 eicosatrienoic, arachidonic or docosahexaenoic acids. Although a 100 microM mixture of palmitic, stearic, oleic and linoleic acid (25:10:50:15) had little effect on the uptake of 10 or 20 microM eicosapentaenoic acid, less of this acid was channeled into endothelial phospholipids. However, the fatty acid mixture did not prevent the inhibitory effect of eicosapentaenoic acid on prostaglandin I2 formation in response to either arachidonic acid or ionophore A23187. An 8 h exposure to eicosapentaenoic acid was required for the inhibition to become appreciable and, after 16 h, prostaglandin I2 production was reduced by as much as 60%. These findings indicate that the capacity of aortic endothelial cells to produce prostaglandin I2 is decreased by continuous exposure to eicosapentaenoic acid. Even if the eicosapentaenoic acid is present as a small percentage of a physiologic fatty acid mixture, it is still readily incorporated into endothelial phospholipids and retains its inhibitory effect against endothelial prostaglandin I2 formation. Therefore, these actions may be representative of the in vivo effects of eicosapentaenoic acid on the endothelium.     

Modification of CaCo-2 cell membrane fatty acid composition by eicosapentaenoic acid and palmitic acid: effect on cholesterol metabolism

Membrane fatty acid composition of CaCo-2 cells was modified by incubating the cells for 8 days in medium containing 100 microM eicosapentaenoic acid or palmitic acid. The effect of membrane fatty acid changes on cholesterol metabolism was then studied. Cells incubated with eicosapentaenoic acid had significant changes in membrane fatty acid composition with an accumulation of 20:5 and 22:5 and a reduction in monoenoic fatty acids compared to cells grown in palmitic acid. Intracellular cholesteryl esters could not be detected in CaCo-2 cells grown in the presence of the n-3 polyunsaturated fatty acid. In contrast, cells incubated with the saturated fatty acid contained 2 micrograms/mg protein of cholesteryl esters. Cells grown in eicosapentaenoic acid, however, accumulated significantly more triglycerides compared to cells modified with palmitic acid. The rate of oleic acid incorporation into triglycerides was significantly increased in cells incubated with eicosapentaenoic acid. CaCo-2 cells modified by eicosapentaenoic acid had lower rates of HMG-CoA reductase and ACAT activities compared to cells modified with palmitic acid. The incorporation of the two fatty acids into cellular lipids also differed. Palmitic acid was predominantly incorporated into cellular triglycerides, whereas eicosapentaenoic acid was preferentially incorporated into phospholipids with 60% of it in the phosphatidylethanolamine fraction. The data indicate that membrane fatty acid composition is significantly altered by growing CaCo-2 cells in eicosapentaenoic acid. These modifications in membrane fatty acid saturation are accompanied by a decrease in the rates of cholesterol synthesis and cholesterol esterification.     

Metabolism of n-3 polyunsaturated fatty acids and modification of phospholipids in cultured rabbit aortic smooth muscle cells

The metabolism of the linolenic acid family (n-3) of fatty acids, e.g., linolenic, eicosapentaenoic, and docosahexaenoic acids, in cultured smooth muscle cells from rabbit aorta was compared to the metabolism of linoleic and arachidonic acids. There was a time-dependent uptake of these fatty acids into cells for 16 hr (arachidonic greater than docosahexaenoic, linoleic, eicosapentaenoic greater than linolenic), and the acids were incorporated mainly into phospholipids and triglycerides. Eicosapentaenoic and arachidonic acids were incorporated more into phosphatidylethanolamine and phosphatidylinositol plus phosphatidylserine and less into phosphatidylcholine than linolenic and linoleic acids. Docosahexaenoic acid was incorporated into phosphatidylethanolamine more than linolenic and linoleic acids and into phosphatidylinositol plus phosphatidylserine less than eicosapentaenoic and arachidonic acids. Added linolenic acid accumulated mainly in phosphatidylcholine and did not decrease the arachidonic acid content of any phospholipid subfraction. Elongation-desaturation metabolites of linoleic acid did not accumulate. Cells treated with eicosapentaenoic acid accumulated both eicosapentaenoic and docosapentaenoic acids mainly in phosphatidylethanolamine and the arachidonic acid content was decreased. Added docosahexaenoic acid accumulated mainly in phosphatidylethanolamine and decreased the content of both arachidonic and oleic acids. The following conclusions are drawn from these results. The three n-3 fatty acids are utilized differently in phospholipids. The arachidonic acid content of phospholipids is reduced by eicosapentaenoic and docosahexaenoic acids, but not by linolenic acid. Smooth muscle cells have little or no desaturase activity, but have significant elongation activity for polyunsaturated fatty acids.     

Effect of dietary fish oil on platelet aggregability: comparison between two oils with different eicosapentaenoic to arachidonic acid ratio.

Rats, acclimatized on a control diet, were fed for 60 days with diets, supplemented with 10% fat of either marine Hilsa fish (Hilsa ilisa) or fresh-water Chital fish (Notopterus chitala). The percentage of eicosapentaenoic acid in chital oil diet was 0.57 times that of the hilsa oil diet, but the eicosapentaenoic to arachidonic acid ratio in the latter (4.08) was 3.2 times that of the former (1.27). Otherwise these two diets were comparable in respect to total saturated, monounsaturated and n-3 polyunsaturated fatty acid contents. Results showed that of the two only hilsa oil diet could significantly lower platelet aggregability and in vitro thromboxane production, through replacement of arachidonic acid in platelet phospholipid by eicosapentaenoic acid. The antithrombic criteria of the oil seems to be a combination of low arachidonic acid content and high eicosapentaenoic to arachidonic acid ratio.     

Beneficial effect of fish oil on blood viscosity in peripheral vascular disease.

Reports suggest that the low incidence of ischaemic heart disease in Greenlandic Eskimos is related to the effect of a diet rich in eicosapentaenoic acid on platelet reactivity and plasma lipid concentrations. A double blind randomised investigation was therefore conducted of the effects on blood viscosity of dietary supplementation with an oil rich in this fatty acid (1.8 g/day, given as fish oil) and an eicosapentaenoic acid poor oil (as corn/olive oil) in patients with peripheral arterial disease. A statistically significant reduction in whole blood viscosity was observed at seven weeks in those patients receiving the eicosapentaenoic acid rich oil. No changes in plasma viscosity, haemoglobin concentration, packed cell volume, or platelet count were seen. A significant fall in plasma triglyceride concentration was also noted only in the patients receiving oil rich in eicosapentaenoic acid; plasma concentrations of cholesterol and high density lipoprotein cholesterol were unchanged. It is concluded that rheological changes that result from a diet rich in eicosapentaenoic acid may contribute to the suggested protective effects of such a diet against arterial disease and that such changes are of potential therapeutic importance in established arterial disease.     

Dietary effect of EPA-rich and DHA-rich fish oils on the immune function of Sprague-Dawley rats

The dietary effect of fish oils (FOs) rich in eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on the immune function of Sprague-Dawley rats was compared with that of safflower oil. After 3 weeks of feeding at the 10% level of a dietary fat, the IgG and IgM production by splenocytes and IgG production by mesenteric lymph node (MLN) lymphocytes were significantly higher in the FO-fed rats, while no significant difference was found in IgA or IgE productivity by both the spleen and MLN lymphocytes. In the FO-fed rats, peritoneal exudate cells released a lower amount of LTB4, reflecting their lower arachidonic acid level, and a higher amount of LTB5, reflecting their higher EPA level in phospholipids. On these EPA-rich FO exerted a stronger effect than DHA-rich FO immune functions.     

Urinary excretion of diols derived from eicosapentaenoic acid during n-3 fatty acid ingestion by man.

Epoxides and fatty acid diols derived from arachidonate by the action of cytochrome P-450 appear in human urine and have biological activities. Dietary eicosapentaenoic acid gives rise to prostaglandins in vivo, but vascular effects of n-3 supplements do not all correlate with altered types or amounts of in vivo cyclooxygenase products. We investigated whether dietary eicosapentaenoic acid could also be metabolized by cytochrome P-450, by assessing the excretion of its vicinal diols. Utilizing gas chromatography/negative chemical ionization mass spectrometry, we have found that humans ingesting n-3 fatty acids excrete vicinal diols of eicosapentaenoic acid in substantial quantities.     

Dietary fish oil as hepatoprotective agent in Mus musculus

The administration of galactosamine in omega-3 polyunsatu-rated fatty acid (PUFA) supplemented mice resulted in lesser amount of damage in the liver tissue compared to the mice without prior supplementation of fish oil. Only 50% elevation in the plasma total bilirubin was detected in omega-3 supplemented mice injected with galactosamine over those supplemented with omega-3 without galactosomine injection. The results suggest that very long chain omega-3 PUFA like eicosapentaenoic and docosahexaenoic acid may act as preventive agent for hepatic cirrhosis in Mus musculus.     

Changes in the amount of fatty acids produced by Melosira dastei culture on synthetic medium

Some of fatty acids contents of the marine Diatom, Melosira dastei, were characterized. The major constituents of them are palmitic, palmitoleic and eicosapentaenoic acids. Linolenic acid type appeared to be a minor constituent. When that Diatom is cultured on an artificial medium, it might be considered as a potential source of valuable eicosapentaenoic acid. Even when the cells concentration is low, in batch cultures, eicosapentaenoic acid constitutes up to 5% of the dry weight and reaches about 20% of the triglycerids content. This level might be improved.     

Teteraene and pentaene leukotrienes: Selective production from murine mastocytomo cells after dietary manipulation

A neoplastic mast cell tumor was grown in mice which had been raised since birth on a diet enriched with eicosapentaenoic acid. Intact harvest mastocytoma cells were stimulated with calcium ionophpore A23187 to produce lipoxygenase products from the polyunsaturated fatty acids liberated from the cellular membranes. Leukotriene B₄, B₅, C₄ and C₅ were isolated and characterized by HPLC retention time, ultraviolet absorption spectrometry and mass spectrometry. The arachidonic acid content of the mast cell tumor lipids was altered from 9.2 to 3.9 mole% while eicosapentaenoic acid increased from 0.5 to 4.5 mole % in response to the fish oil-supplement diet.The relative amount of arachidonic and eicosapentaenoic acids (3.9 and 4.5 mole % respectively) were associated with similar amounts of LTB₄ and LTP₅ synthesized by the cells. These results suggest that the epoxide leukotrine (LTA) derivative can be made efficiently from either arachidonic or eicosapentaenoic acids when both are present in cellular lipids. In contrast, the ratio of LTC₄ to LTC₅ (10 to 1) indicates that the reaction of LTA with glutathione may be critically dependent upon the structure of the unsaturated fatty acid with the ratio of LTC₄/LTB₄ (2.0) more than 10 times greater than that (0.16) for LTC₅/LTP₅.     

Alteration of arachidonate levels in tick salivary glands by dietary modification of host blood lipids

Tick saliva contains prostaglandins of the 2-series, believed to facilitate bloodmeal acquisition. Because ticks cannot synthesize the prostaglandin precursor, arachidonic acid, investigations were undertaken to study the uptake, incorporation, and distribution of arachidonic acid in the salivary glands of the lone star tick in vitro and in vivo. Uptake of [³H]arachidonate by isolated salivary glands was reduced in the presence of low concentrations of arachidonic or eicosapentaenoic acids, but much higher, non-physiological concentrations of oleic and linoleic acids were required to inhibit [³H]arachidonate uptake. The incorporation of [³H]arachidonate into triglycerides increased at high concentrations of arachidonic or eicosapentaenoic acid, but not at any concentration of oleic or linoleic acid. Eicosatetraynoic acid greatly inhibited [³H]arachidonate uptake and increased intracellular unesterified [³H]arachidonic acid. Guinea pigs fed hydrogenated coconut oil, safflower/primrose oil, or fish oil exhibited altered blood lipids; notably increased levels of eicosapentaenoic acid when fed fish oil. Salivary gland lipids in ticks fed on these hosts were also altered. Ticks parasitizing fish oil-fed guinea pigs contained high levels of eicosapentaenoic acid with a 30% reduction in arachidonate levels. The results demonstrated that eicosapentaenoic acid in the host diet had profound effects on arachidonate assimilation by tick salivary glands, which could lead to altered prostaglandin content in tick saliva. © 1996 Wiley-Liss, Inc.     

Fish oil-enriched diet is mucosal protective against acetic acid-induced colitis in rats.

Products of arachidonic acid metabolism are elevated in patients with inflammatory bowel disease and this elevation is correlated with disease activity. Eicosapentaenoic acid competes with arachidonic acid and alters eicosanoid biosynthesis. In this experiment, the possibility that eicosapentaenoic acid could be used in the treatment of inflammatory bowel disease was investigated by determining the effect of 6 weeks of a fish oil-supplemented diet, enriched in eicosapentaenoic acid, on colonic and ileal morphology, histology, and in vivo fluid absorption in rats with 4% acetic acid-induced colitis. The results of an eicosapentaenoic acid-enriched diet were compared with results of saturated and polyunsaturated fatty acid-enriched diets. In rats with misoprostol pretreated acetic acid-induced colitis, an eicosapentaenoic acid-enriched diet reversed net colonic fluid secretion to absorption and prevented macroscopic and histologic injury, compared with saturated and poly-unsaturated fatty acid-enriched diets, which did not. The fish oil mucosal protective effect occurred in the presence of a 30-fold enhancement of PGE2 synthesis. In rats with non-misoprostol pretreated acetic acid-induced colitis, an eicosapentaenoic acid-enriched diet returned ileal fluid absorption to control levels, as compared with saturated and polyunsaturated fatty acid-enriched diets, which did not. In conclusion, a fish oil (eicosapentaenoic acid)-enriched diet, but not a saturated- or a polyunsaturated-enriched diet, protected colonic and ileal net fluid absorption in an experimental model of inflammatory bowel disease.