Role of triglycerides in endothelial cell arachidonic acid metabolism

Arachidonic acid was incorporated into triglycerides by cultured bovine endothelial cells in a time- and concentration-dependent manner. At 75 microM or higher, more arachidonic acid was incorporated into triglycerides than into phospholipids. The triglyceride content of the cells increased as much as 5.5-fold, cytoplasmic inclusions appeared, and arachidonic acid comprised 22% of the triglyceride fatty acids. Triglyceride turnover occurred during subsequent maintenance culture; there was a 60% decrease in the radioactive arachidonic acid contained in triglycerides and a 40% decrease in triglyceride content in 6 hr. Most of the radioactivity was released into the medium as free fatty acid. The turnover of arachidonic acid, but not oleic acid in cellular triglycerides, decreased when supplemental fatty acid was added to the maintenance medium. Incorporation and turnover of radioactive arachidonic acid in triglycerides also was observed in human skin fibroblasts, 3T3-L1 cells, and MDCK cells. Other fatty acids were incorporated into triglycerides by the endothelial cells; the amounts after a 16-hr incubation with 50 microM fatty acid were 20:3 greater than 20:4 greater than 18:1 greater than 18:2 greater than 22:6 greater than 16:0 greater than 20:5. These findings indicate that triglyceride formation and turnover can play a role in the fatty acid metabolism of endothelial cells and that arachidonic acid can be stored in endothelial cell triglycerides.     

Lipid and cell metabolic changes associated with essential fatty acid enrichment of articular chondrocytes

Observations of impaired chondrocyte metabolism in essential fatty acid (EFA) deficiency as well as EFA protection against development of osteoarthrosis in inbred mice suggest the existence of a relationship between EFA, chondrocyte metabolism, and cartilage degeneration. To explore this relationship further, the fatty acid content of lipids in normal fetal bovine chondrocytes was manipulated by in vitro exposure to media supplemented with 100 microM arachidonic acid (20:4) or oleic acid (18:1). Chondrocytes rapidly and differentially incorporated both fatty acids into their lipid pools. The predominant acceptor was triacylglycerols. A 980% enrichment of arachidonic acid was associated with increased concentrations of fatty acids, increased 35SO4 and [3H]proline incorporation into matrix macromolecules (170% and 54-103%, respectively), and a 24-fold elevation in chondrocyte prostaglandin synthesis. No metabolic effects elicited observed in cells enriched by 377% with 18:1 oleic acid. The metabolic effects elicited by 20:4 arachidonic acid were abolished by pretreatment of cells with indomethacin, suggesting that the cellular responses to essential fatty acid loading may be associated with induced increases in prostaglandin synthesis. The data indicate that excessive in vitro accumulation of arachidonic acid is associated with an increase in synthetic activity that is causally related to increased prostaglandin synthesis and elevated levels of cellular fatty acids.     

Augmentation of unesterified arachidonic acid in the renal inner medulla of dexamethasone-treated rats. Relationship to altered triglyceride metabolism

The present study was designed to investigate the effect of dexamethasone treatment for 2 weeks (2.5 mg/kg/week, subcutaneously) on the level of unesterified fatty acids, particularly arachidonic acid, in the renal medulla of rats, and to relate the observed effect to changes in the tissue concentration and the fatty acid composition of renal medulla phospholipids and triglycerides. Dexamethasone treatment caused an increase in the renal inner medulla level of unesterified fatty acids, including arachidonic acid, that was associated with a reduction of triglycerides and of arachidonic acid esterified into triglycerides, and with an increase in the rate of fatty acids esterification into triglycerides. In contrast, dexamethasone treatment did not affect the renal medulla concentration of phospholipids, the arachidonic acid content of renal medulla phospholipids, or the rate of esterification of fatty acids into renal medulla phospholipids. In the face of increased fatty acid esterification into triglycerides, the finding of reduced triglyceride levels in the renal medulla of dexamethasone-treated rats suggests excessive triglyceride breakdown. If so, fatty acids including arachidonic acid liberated from triglycerides may contribute to elevation of unesterified fatty acid levels in the renal medulla during dexamethasone treatment. The increased level of free arachidonic acid in the renal medulla of dexamethasone-treated rats may explain in part the reported effect of this steroid in increasing urinary prostaglandins.     

Membrane fatty acid composition and endothelial cell functional properties

In order to study the influence of endothelial cell fatty acid composition on various membrane related parameters, several in vitro methods were developed for manipulating the fatty acid content of human endothelial cell membranes. Changes in membrane fatty acid profile were induced by using fatty acid modified lipoproteins or free fatty acids. The largest changes in endothelial fatty acid composition were obtained by culturing the cells in media supplemented with specific free fatty acids. An increase in arachidonic acid content of endothelial phospholipids was induced by supplementation with saturated fatty acids or with arachidonic acid itself. A decrease in arachidonic acid content was obtained by supplementation with other unsaturated fatty acids. Under the experimental conditions used endothelial cells showed a low desaturase activity and a high elongase activity. Considerable alterations in membrane fatty acid composition did not greatly influence certain membrane related parameters such as polymorphonuclear leukocyte adherence and endothelial cell procoagulant activity. In general, for fatty acid modified endothelial cells an association between endogenous arachidonic acid content and total production of eicosanoids was found. This study demonstrates that considerable changes in membrane fatty acid profile affect endothelial cell arachidonic acid metabolism, but it also illustrates homeostasis at the level of endothelial cell functional activity.     

Arachidonic Acid Inhibits Choline Uptake and Depletes Acetylcholine Content in Rat Cerebral Cortical Synaptosomes

The effects of arachidonic acid on [3H]choline uptake, on [3H]acetylcholine accumulation, and on endogenous acetylcholine content and release in rat cerebral cortical synaptosomes were investigated. Arachidonic acid (10-150 microM) produced a dose-dependent inhibition of high-affinity [3H]choline uptake. Low-affinity [3H]choline uptake was also inhibited by arachidonic acid. Fatty acids inhibited high-affinity [3H]choline uptake with the following order of potency: arachidonic greater than palmitoleic greater than oleic greater than lauric; stearic acid (up to 150 microM) had no effect. Inhibition of [3H]choline uptake by arachidonic acid was reversed by bovine serum albumin. In the presence of arachidonic acid, there was an increased accumulation of choline in the medium, but this did not account for the inhibition of [3H]choline uptake produced by the fatty acid. Arachidonic acid inhibited the synthesis of [3H]acetylcholine from [3H]choline, and this inhibition was equal in magnitude to the inhibition of high-affinity [3H]choline uptake produced by the fatty acid. A K+-stimulated increase in [3H]acetylcholine synthesis was inhibited completely by arachidonic acid. Arachidonic acid also depleted endogenous acetylcholine stores. Concentrations of arachidonic acid and hemicholinium-3 that produced equivalent inhibition of [3H]choline uptake also produced equivalent depletion of acetylcholine content. In the presence of eserine, arachidonic acid had no effect on acetylcholine release. The results suggest that arachidonic acid may deplete acetylcholine content by inhibiting high-affinity choline uptake and subsequent acetylcholine synthesis. This raises the possibility that arachidonic acid may play a role in the impairment of cholinergic transmission seen in cerebral ischemia and other conditions in which large amounts of the free fatty acid are released in brain.     

Increased levels of a particular phosphatidylcholine species in senescent human dermal fibroblasts in vitro

Plasma membranes are essential components of living cells, and phospholipids are major components of cellular membranes. Here, we used liquid chromatography/mass spectrometry to investigate changes in the membrane phospholipid content that occur in association with aging. Our results indicate that the levels of a particular species of phosphatidylcholine comprised of stearic acid and arachidonic acid increased with age. To determine the reason for the increased levels of this particular phosphatidylcholine, we examined the effect of highly unsaturated fatty acids, such as arachidonic acid and eicosapentaenoic acid, on cellular aging. Applied arachidonic acid was incorporated into phosphatidylcholine molecules, but neither arachidonic acid nor other related unsaturated fatty acids had any effect. We conclude that increased levels of this distinctive phosphatidylcholine are a result of in vitro senescence.     

The role of arachidonic acid in vasogenic brain edema

Arachidonic acid is released rapidly from cellular membrane phospholipids after pathological insults associated with the delayed development of brain edema. Intracerebral injection of arachidonic acid caused significant increases in brain water and sodium content with decreases in potassium content and Na+,K+-ATPase activity. The 125I-labeled bovine serum albumin spaces in brain (a measure of blood-brain barrier permeability) rose threefold 24 h after arachidonic acid injection. There was gross and microscopic evidence of edema. Saturated fatty acids and monounsaturated fatty acids were not effective. These data indicate that the endothelial cells of the blood-brain barrier are target sites for the action of arachidonic acid. It is hypothesized that the increased permeability of endothelial cells to macromolecules and water results from alterations of membrane phospholipids and increased vesicular transport, changes that are responsible for the delayed development of vasogenic edema.     

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 ENVIRONMENTAL CONDITIONS ON FATTY ACID COMPOSITION OF THE RED ALGA PORPHYRIDIUM CRUENTUM: CORRELATION TO GROWTH RATE1

The lipid and fatty acid composition of Porphyridium cruentum was determined as a function of light intensity, temperature, pH, and salinity. In cultures cultivated at the optimal temperature under non-limiting light conditions, eicosapentaenoic acid was the main polyunsaturated fatty acid. When growth rate was reduced by decreased light intensity, increased cell concentration, suboptimal temperature, suboptimal pH, or increased salinity, the content of eicosapentaenoic acid decreased and that of arachidonic acid increased, the latter becoming the major polyunsaturated fatty acid.     

Fatty acid changes in liver and plasma lipid fractions after safflower oil was fed to rats deficient in essential fatty acids

1. Fatty acid patterns of liver and plasma triglycerides, phospholipids and cholesteryl esters were determined at intervals during 24hr. after essential fatty acid-deficient rats were given one feeding of linoleate (as safflower oil). 2. Liver triglyceride, phospholipid and cholesteryl ester fatty acid compositions did not change up to 7hr. after feeding. Between 7 and 10hr., linoleic acid began to increase in all fractions, but arachidonic acid did not begin to rise in the phospholipid until 14-19hr. after feeding. 3. Oleic acid and eicosatrienoic acid in liver phospholipid began to decline at about the time that linoleic acid increased, i.e. about 9hr. before arachidonic acid began to increase. 4. Changes in linoleic acid, arachidonic acid and eicosatrienoic acid in phosphatidylcholine resembled those of the total phospholipid. Phosphatidylethanolamine had a higher percentage content of arachidonic acid before the linoleate was given than did phosphatidylcholine, and after the linoleate was given the fatty acid composition of this fraction was little changed. 5. The behaviour of the plasma lipid fatty acids was similar to that of the liver lipids, with changes in linoleic acid, eicosatrienoic acid and arachidonic acid appearing at the same times as they occurred in the liver. 6. The results indicated that linoleic acid was preferentially incorporated into the liver phospholipid at the expense of eicosatrienoic acid and oleic acid. The decline in these fatty acids apparently resulted from their competition with linoleic acid for available sites in the phospholipids rather than from any direct replacement by arachidonic acid.     

Effect of temperature on fatty acid composition in each lipid fraction of Spirometra erinaceieuropaei plerocercoids

The effects of temperature and host fatty acids on the fatty acid contents of Spirometra erinaceieuropaei plerocercoids were investigated to clarify their role in sparganosis. After 24 hr incubation at 18 C in host snake serum, omega6 series fatty acids, especially arachidonic acid in the phospholipid fraction of the plerocercoids, increased compared with those of plerocercoids incubated at 37 C. The changes in the ratio of polyunsaturated to saturated fatty acids in the phospholipid fraction of plerocercoids incubated in physiological saline for 6 hr at 10 C were almost the same as the changes at 37 C. The ratio of polyunsaturated to saturated fatty acids of the triglyceride fraction showed almost opposite change versus the phospholipid fraction. The percentage of arachidonic acid in the phospholipid fraction of plerocercoids increased during the first 3 hr of incubation and then decreased, regardless of temperature. At 37 C, the percentage of arachidonic acid in the free fatty acid fraction fell for the first 3 hr of incubation and was significantly elevated at the end of the 6-hr incubation. At 10 C, however, arachidonic acid in the free fatty acid fraction decreased for the first hour of incubation, increased at 3 hr of incubation, then decreased again. These results suggest that fatty acids of the plerocercoids are frequently exchanged between fractions. Plerocercoids can mobilize arachidonic acid to the free fatty acid fraction more quickly at lower temperature than at higher temperature. They may utilize mobilized arachidonic acid early in the infection stage to produce prostaglandins. Alternatively, they can incorporate arachidonic acid into the phospholipid fraction again when arachidonic acid is readily available in the environment.     

Lipid metabolism and production of progesterone and prostaglandin F during induced regression of porcine corpora lutea

Patterns of luteal lipid and arachidonic acid accumulation were examined in relation to luteal progesterone and prostaglandin F synthesis in 30 sows and gilts between days 8 and 18 of the estrous cycle. Net release of progesterone from luteal tissue declined from 722 ng/100 mg tissue at day 8 to 81 ng/100 mg tissue at day 18. Although statistical significance was not present, net prostaglandin F release increased slightly from 8.6 to 13.9 ng/100 mg tissue. Luteal free cholesterol, esterified cholesterol, and free fatty acid contents did not change between days 8 and 18 whereas triglycerides accumulated rapidly between days 14 and 18 of the estrous cycle. Phospholipids increased between days 8 and 12, plateaued at 20.2 mg/g between days 14 and 16, and decreased to 15.4 mg/g on day 18. Between days 12 and 18, arachidonic acid increased from 19.4 to 34.8% in cholesterol esters, from 10.1 to 22.5% in triglycerides, and from 12.3 to 27.2% in luteal free fatty acids. Arachidonic acid in luteal phospholipids increased from 21.3 to 25.1% between days 14 and 16 of the estrous cycle. Luteal regression was associated with conservation of arachidonic acid. Based on blood plasma lipid fatty acid compositions, the corpus luteum elongated and desaturated essential fatty acids. Within porcine corpora lutea, calculated free arachidonic acid content was adequate for maintenance of prostaglandin synthesis.     

The influence of mono- and divalent cations on the cardiac metabolism of arachidonic acid

Our previous study indicated that, in the isolated rabbit heart, perfusion with Ca2+ free Krebs Henseleit buffer (KHB) results in increased conversion of exogenous arachidonic acid to PGE2 and 6-keto-PGF1 alpha, probably as the result of increased availability of substrate to cyclooxygenase. Since perfusion with Ca2+ free buffer is known to cause alterations in the cardiac content of various mono- and divalent cations, the present study was performed to determine: a) The relationship between the conversion of exogenous arachidonic acid to prostaglandins and cardiac content of Na+, K+, Ca2+ and Mg2+; and b) Whether enhanced arachidonic acid conversion to prostaglandins during Ca2+ free perfusion is due to reduced incorporation of this fatty acid into tissue lipids. Perfusion of the rabbit heart with Ca2+ free buffer produced a significant reduction in the tissue content of Na+, K+, Ca2+ and Mg2+. However, the production of 6-keto-PGF1 alpha from exogenous arachidonic acid was linearly correlated with tissue Mg2+. These observations, together with our finding that perfusion with Ca2+ free KHB reduced the incorporation of [3H] arachidonic acid into tissue lipids, suggests that Ca2+ free perfusion may, by reducing the activity of arachidonyl CoA synthetase (a Mg2+ dependent enzyme), decrease the acylation of arachidonic acid into lipids, thus increasing the availability of arachidonic acid to cyclooxygenase.     

Substance P induces alterations on cerebral lipids involved in membrane fluidity

This study was undertaken to examine the variations in rat brain of cholesterol, phospholipid and phospholipid fatty acid composition induced by substance P. The cholesterol content was increased by substance P; concomitantly, an increase of the ratio cholesterol/phospholipid was observed. These changes do not appear to be responsible of the stimulation observed in Na+,K+-ATPase activity by substance P action. Phospholipid fatty acid analysis revealed that the peptide induced a decrease in both linoleic and arachidonic acids content.     

Effect of fatty acid modification on prostaglandin production by cultured 3T3 cells

We have investigated the extent to which modifications in the essential fatty acid content of mammalian cells can affect prostaglandin production. Swiss mouse 3T3 cells stimulated with the calcium ionophore A23187 produced 1.7 to 7 times more prostaglandin E(2) (PGE(2)) when the cultures were supplemented with linoleic acid. Increases in PGE(2) production as a result of linoleic acid supplementation occurred under all culture conditions except during the first 24 hr after attachment, when prostaglandin production was very high. Arachidonic acid supplementation produced a similar enhancement in the capacity of the cells to produce PGE(2), but no appreciable increase occurred when the cultures were supplemented with oleic acid. The phospholipids of the cells exposed to the linoleate-enriched medium contained 4 times more arachidonic acid and twice as much linoleic acid as compared with the corresponding controls. The choline phosphoglycerides were most highly enriched in arachidonic acid, but 2- to 3-fold increases also occurred in the inositol and ethanolamine phosphoglycerides. When cultures initially enriched with linoleic acid were transferred to an unsupplemented medium, the fatty acid composition as well as the capacity of the cells to produce PGE(2) reverted almost to control values. The amount of exogenous arachidonic acid converted to PGE(2) as measured by radioimmunoassay also was greater when the cells were enriched with linoleic acid. Studies with radioactive arachidonic acid indicated that the distribution of prostaglandin metabolites was not affected appreciably by linoleic acid enrichment. These findings suggest that at least two factors contribute to the increased capacity of the cultures supplemented with linoleate to produce PGE(2). One is enrichment of the phospholipid substrate pools with arachidonic acid. The other is an increased ability of the cells to synthesize PGE(2) from unesterified arachidonic acid, perhaps because the prostaglandin-forming enzymes are more active.-Denning, G. M., P. H. Figard, and A. A. Spector. Effect of fatty acid modification on prostaglandin production by cultured 3T3 cells.     

Fatty acid specificity of acyl-CoA synthetase in rat glomeruli

The fatty acid specificity of acyl-CoA synthetase in rat glomeruli for physiologically and pathologically important long-chain fatty acids was studied. The apparent Michaelis constants (Km) for substrate fatty acids increased in the order, linolenic less than linoleic less than eicosapentaenoic less than arachidonic less than oleic less than palmitic acid. The maximum velocities with these fatty acids decreased in the order, oleic greater than linoleic greater than palmitic (approximately equal to) linolenic greater than arachidonic greater than eicosapentaenoic acid. The syntheses of radioactive arachidonyl-CoA and palmitoyl-CoA from radioactive arachidonic and palmitic acid, respectively, were both inhibited by all fatty acids mentioned above including the substrate fatty acids, their inhibitory effects being inversely correlated with their apparent Km values. These results suggest that the enzyme in glomeruli has a unique specificity for fatty acids and that there is no arachidonic acid-specific acyl-CoA synthetase in glomeruli. The possible contribution of the glomerular enzyme with this specificity to the abnormal fatty acid levels in diabetic animals is discussed.     

Dietary fat and the diabetic state alter insulin binding and the fatty acyl composition of the adipocyte plasma membrane.

Control and diabetic rats were fed on semi-purified high-fat diets providing a polyunsaturated/saturated fatty acid ratio (P/S) of 1.0 or 0.25, to examine the effect of diet on the fatty acid composition of major phospholipids of the adipocyte plasma membrane. Feeding the high-P/S diet (P/S = 1.0) compared with the low-P/S diet (P/S = 0.25) increased the content of polyunsaturated fatty acids in membrane phospholipids in both control and diabetic animals. The diabetic state decreased the content of polyunsaturated fatty acids, particularly arachidonic acid, in adipocyte membrane phospholipids. The decrease in arachidonic acid in membrane phospholipids of diabetic animals tended to be normalized to within the control values when high-P/S diets were given. For control animals, altered plasma-membrane composition was associated with change in insulin binding, suggesting that change in plasma-membrane composition may have physiological consequences for insulin-stimulated functions in the adipocyte.     

Association of calmodulin inhibition, erythrocyte membrane stabilization and pharmacological effects of drugs

Isolated liver cells from rats fed a diet deficient in essential fatty acids were used to study the oxidation, esterification and, especially, the desaturation and chain elongation of [1-14C]linoleic acid. 14C-labelled arachidonic acid (20:4) and smaller amounts of eicosatrienoic acid (20:3) were recovered mainly in the phospholipids, while gamma-linolenic acid (18:3) was found in both the phospholipids and the triacylglycerol fraction. Lactate strongly increased the formation of arachidonic acid, which was found mainly in the phosphatidylcholine and the phosphatidylinositol fractions. Lactate reduced the amounts of gamma-linolenic acid. Glucagon and (+)-decanoylcarnitine reduced the formation of arachidonic acid, and (+)-decanoylcarnitine increased the incorporation of gamma-linolenic acid especially, in the triacylglycerol fraction. Increasing concentrations of the [1-14C]linoleic acid substrate increased the formation of arachidonic acid and of the other chain-elongated or desaturated fatty acids. Lactate also stimulated the formation of arachidonic acid in liver cells from animals fed adequate amounts of essential fatty acids. It is suggested that dietary and hormonal factors which can change the intracellular levels of malonyl-CoA may influence both the ratio of arachidonic acid/gamma-linolenic acid formed and the total amounts of desaturated and chain-elongated fatty acids formed from linoleic acid.     

Lipid and arachidonic acid accumulation in naturally regressing porcine corpora lutea

Patterns of luteal lipid and arachidonic acid accumulation were examined in relation to luteal progesterone and prostaglandin F synthesis in 30 sows and gilts between days 8 and 18 of the estrous cycle. Net $\text{in vitro}$ release of progesterone from luteal tissue declined from 722 ng/100 mg tissue at day 8 to 81 ng/100 mg tissue at day 18. Although statistical significance was not present, net prostaglandin F release increased slightly from 8.6 to 13.9 ng/100 mg tissue. Luteal free cholesterol, esterified cholesterol, and free fatty acid contents did not change between days 8 and 18 whereas triglycerides accumulated rapidly between days 14 and 18 of the estrous cycle. Phospholipids increased between days 8 and 12, plateaued at 20.2 mg/g between days 14 and 16, and decreased to 15.4 mg/g on day 18. Between days 12 and 18, arachidonic acid increased from 19.4 to 34.8% in cholesterol esters, from 10.1 to 22.5% in triglycerides, and from 12.3 to 27.2% in luteal free fatty acids. Arachidonic acid in luteal phospholipids increased from 21.3 to 25.1% between days 14 and 16 of the estrous cycle. Luteal regression was associated with conservation of arachidonic acid. Based on blood plasma lipid fatty acid compositions, the corpus luteum elongated and desaturated essential fatty acids. Within porcine corpora lutea, calculated free arachidonic acid content was adequate for maintenance of prostaglandin synthesis.     

The health implications of changing linoleic acid intakes

Linoleic acid is the most prominent polyunsaturated fatty acid (PUFA) in the Western diet. It is virtually found in every food we eat and is the predominant PUFA in land-based meats, dairy, vegetables, vegetable oils, cereals, fruits, nuts, legumes, seeds and breads. Because linoleic acid is the metabolic precursor of arachidonic acid and bioactive eicosanoids derived from arachidonic acid, there is concern that dietary linoleic acid could augment tissue arachidonic acid content, eicosanoid formation and subsequently enhance the risk of and/or exacerbate conditions associated with acute and chronic diseases (i.e., cancers, cardiovascular disease, inflammation, neurological disorders, etc.). The following series of papers examines the impact of modifying dietary levels of linoleic acid on health outcomes. The authors were asked to start with current intakes of linoleic acid (adults) and determine if health outcomes would change if linoleic acid intake increased or decreased. The authors addressed changes in tissue arachidonic acid content and eicosanoid formation, cardiovascular disease, inflammation, and psychiatric disorders.