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Platelet aggregation in humans is affected by replacement of dietary linoleic acid with oleic acid.

The effect of concentrations of linoleic acid (LA) on platelet aggregation was measured in seven healthy adult males. Subjects were randomly divided into two groups; these groups were fed natural food diets of identical composition except that one was high in LA (11.5% of energy) and low in oleic acid (OA) (7.4% of energy), the other was low in LA (4.5% of energy) and high in OA (15.7% of energy). The thresholds of ADP- and collagen-induced platelet aggregation were increased significantly by the high LA diet even though the intake of total fat and saturated fatty acids did not differ in these diets.

Adenosine Diphosphate↗

A facile reactor process for producing 7,10-dihydroxy-8(E)-octadecenoic acid from oleic acid conversion by Pseudomonas aeruginosa.

Pseudomonas aeruginosa strain PR3 (NRRL B-18602) converts oleic acid to a novel compound, 7,10-dihydroxy-8(E)-octadecenoic acid (DOD). The bioconversion was scaled up in a 7-l bench-top, stirred-batch reactor to produce DOD for testing of potential industrial uses. Aeration was supplied continuously from the top through two ports on the headplate and periodically through a bottom sparger, in conjunction with the use of marine impellers for agitation. This unique aeration arrangement maintained the dissolved O2 concentration in the 40-60% range during the period of maximal bioconversion and it also avoided excessive medium foaming during the reaction. Furthermore, the level of dissolved O2 in the first 24 h of reaction played an important role in the initial rate of DOD production. DOD production reached a plateau after 72 h with a yield up to 100 g (or 50% recovery) from a total of 9 l medium from two reactors run simultaneously. The final culture broth was processed using newly adapted procedures in the pilot plant that included crystallization of DOD from ethyl acetate solution at -15 degrees C. The newly developed bioprocess will serve as a platform for the scale-up production of other value-added products derived from vegetable oils and their component fatty acids.

Bioreactors↗

Differential effects of dietary intake of palmitic acid and oleic acid on oxygen consumption during and after exercise.

Our previous studies suggest that diets varying in palmitic acid (PA) and oleic acid (OA) content may affect energy expenditure and fat oxidation differentially. We hypothesized that, compared with a high-OA diet, a high-PA diet would lead to lower oxygen consumption during exercise and lower excess postexercise oxygen consumption (EPOC). Adults were randomized to 1 of 2 liquid diets (28 days): HI PA (fat, 40% of energy; PA, 16.8%; OA, 16.4%) (n = 10) or HI OA (fat, 40%; PA, 1.7%; OA, 31.4%) (n = 9). On day 29, the rates of oxygen consumption (V o(2)) and carbon dioxide production were measured during and for 270 minutes after 80 minutes of cycling (60% V o(2 peak)). There was no group difference (HI OA vs HI PA, mean +/- SEM) in fat-free mass (53.8 +/- 4.7 vs 56.9 +/- 3.0 kg), V o(2 peak) (40.7 +/- 2.3 vs 36.6 +/- 3.2 mL/kg per minute), and work during exercise (101 +/- 12 vs 101 +/- 10 W). V o(2) (L/min) during exercise (1.99 +/- 0.22 vs 1.85 +/- 0.19) was significantly different (P = .05) only when corrected for fat-free mass, with which it significantly correlated (r = 0.86; P < .001). During 60 to 270 minutes postexercise, the average EPOC was 9.7% +/- 4.9% of preexercise V o(2) in OA, whereas there was no EPOC present in PA (P = .06 between diets). In conclusion, a high-PA diet appears to lower V o(2) during and after exercise compared with a high-OA diet.

Adolescent↗

Effects of diets enriched in lauric, palmitic or oleic acids on blood coagulation and fibrinolysis.

In this study we compared the effects of specific saturated fatty acids (lauric acid and palmitic acid) with those of a monounsaturated fatty acid (oleic acid) on coagulation and fibrinolytic parameters in healthy women and men. Eighteen women and fourteen men consumed, in random order, three experimental diets, each for six weeks. The diets consisted of solid foods and approximately 70% [28 percent of energy (En%)] of the fat calories was supplied. As determined from duplicate portions, in the lauric acid diet 7.3 En% and in the palmitic acid diet 6.1 En% of oleic acid were exchanged for lauric or palmitic acid, respectively. The lauric acid diet also contained some (average 1.8 En%) more myristic acid. Compared with the oleic acid diet, factor VIIam in the female subjects was 9% higher with the lauric acid diet (P = 0.0036; 95% CI, 3 to 14%) and 10% higher with the palmitic acid diet (P = 0.0011; 95% CI, 5 to 16%). Changes in men were not significant. Plasminogen Activator Inhibitor (PAI-1) activity was higher on the palmitic acid compared with the oleic acid diet (difference between diets of 2.3 U/ml; P = 0.0098; 95% CI, 0.4 to 4.3 U/ml) and the lauric acid diet (difference between diets of 2.2 U/ml; P = 0.0123; 95% CI, 0.2 to 4.1 U/ml). No significant differences between diets were observed for antithrombin III activity, fibrinogen concentrations, fragment 1+2 concentrations, plasminogen or alpha2-antiplasmin activity. From this study, we conclude that diets rich in lauric or palmitic acid, compared with a diet rich in oleic acid, unfavourably influence factor VIIam activity, in a gender specific manner. In addition, the plasminogen activator inhibiting capacity of the plasma is impaired with a palmitic acid rich diet compared with an oleic or lauric acid rich diet.

Adult↗

Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells.

It has been suggested that dietary interventions may improve the effectiveness of cancer chemotherapy. We have examined the combined in vitro cytotoxicity of paclitaxel and the fatty acids gamma-linolenic acid (GLA, 18:3n-6) and oleic acid (OA, 18:1n-9) in human breast carcinoma MDA-MB-231 cells. The effect of fatty acids on paclitaxel chemosensitivity was determined by comparing IC(50) and IC(70) (50 and 70% inhibitory concentrations, respectively) obtained when the cells were exposed to IC(50) and IC(70) levels of paclitaxel alone and fatty acids were supplemented either before or during the exposure to paclitaxel. The 3-4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to determine cell growth inhibition. GLA by itself showed antiproliferative effects, and a possible GLA-paclitaxel interaction at the cellular level was assessed by the isobologram and the combination-index (CI) methods. Isobole analysis at the isoeffect levels of 50 and 70% revealed that drug interaction was predominantly synergistic when GLA and paclitaxel were added concurrently for 24 h to the cell cultures. Interaction assessment using the median-effect principle and the combination-index (CI) method showed that exposure of MDA-MB-231 cells to an equimolar combination of concurrent GLA plus paclitaxel for 24 h resulted in a moderate synergism at all effect levels, consistent with the results of the isobologram analysis. When exposure to GLA (24 h) was followed sequentially by paclitaxel (24 h) only an additive effect was observed. The GLA-mediated increase in paclitaxel chemosensitivity was only partially abolished by Vitamin E, a lipid peroxidation inhibitor, suggesting a limited influence of the oxidative status of GLA in achieving potentiation of paclitaxel toxicity. When OA (a non-peroxidisable fatty acid) was combined with paclitaxel, an enhancement of chemosensitivity was found when OA was used concurrently with paclitaxel, although less markedly than with GLA. Pretreatment of MDA-MB-231 cells with OA for 24 h prior to a 24 h paclitaxel exposure produced greater enhancement of paclitaxel sensitivity at high OA concentrations than the concurrent exposure to OA and paclitaxel. The OA-induced sensitisation to paclitaxel was not due to the cytoxicity of the fatty acid itself. When these observations were extended to three additional breast carcinoma cell lines (SK-Br3, T47D and MCF-7), simultaneous exposure to GLA and paclitaxel also resulted in synergism. GLA preincubation followed by paclitaxel resulted in additivity for all cell lines. Simultaneous exposure to paclitaxel and OA enhanced paclitaxel cytotoxicity in T47D and MCF-7 cells, but not in SK-Br3 cells, whereas preincubation with OA failed to increase paclitaxel effectiveness in all three cell lines. For comparison, the effects of other fatty acids on paclitaxel chemosensitivity were examined: GLA was the most potent at enhancing paclitaxel cytotoxicity, followed by alpha-linolenic acid (ALA; 18:3n.3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), whereas linoleic acid (LA; 18:2n-6) did not increase paclitaxel toxicity. These findings provide experimental support for the use of fatty acids as modulators of tumour cell chemosensitivity in paclitaxel-based therapy.

Antineoplastic Agents, Phytogenic↗

Anti-allergic constituents in the culture medium of Ganoderma lucidum. (I). Inhibitory effect of oleic acid on histamine release.

The chloroform extract from Ganoderma lucidum broth markedly inhibited histamine release from rat peritoneal mast cells. From the active fractions, palmitic acid, stearic acid, oleic acid and linoleic acid were isolated. Oleic acid dose-dependently inhibited the histamine release and 45Ca uptake into mast cells induced by compound 48/80 and A-23187 at concentrations of 5 to 50 microM and 0.5 to 5 microM, respectively. Saturated fatty acids, however, had only a weak inhibitory effect on histamine release. Although linoleic acid and linolenic acid effectively prevented this release, these two compounds caused marked release at concentrations higher than 10 microM and 20 microM, respectively. Oleic acid induces membrane-stabilization in model membrane systems. It was concluded that one of the effective constituents obtainable from the chloroform extract of G. lucidum-cultured broth is oleic acid.

Animals↗

Plasma lipoprotein lipid and Lp[a] changes with substitution of elaidic acid for oleic acid in the diet.

The effect of additional dietary trans fatty acids (7% energy) on plasma lipids was assessed in a double-blind comparison of four separate diets: 1, enriched with butter fat (lauric-myristic-palmitic); 2, oleic acid-rich; 3, elaidic acid-rich; 4, palmitic acid-rich. The total dietary period was 11 weeks and comprised normal foods plus specific fat supplements. In 27 mildly hypercholesterolemic men, total and LDL cholesterol were significantly lower during the 3-week oleic acid-rich diet, and were similar during the other three diets. For the four diets LDL cholesterol levels were in mg/dl: 1, 163; 2, 151; 3, 165; 4, 161. HDL cholesterol was significantly higher with the palmitic acid-rich diet, 42 mg/dl, compared with elaidic acid, 38 mg/dl, which in turn was not lower than with oleic acid, 38 mg/dl. Plasma elaidic acid concentration rose seven-fold with the trans fatty acid diet but did not increase the vulnerability of LDL to oxidative change. The elaidic acid-rich diet led to significant elevations in the level of Lp[a] compared to all the other test diets. The Lp[a] level increased to 296 +/- 220 U/l in the elaidic acid-rich period from 235 +/- 182 (mean +/- SD) in the first ("butter") period (P less than 0.001) compared with 249 +/- 204 in the palmitic acid period (P less than 0.001) and 236 +/- 201 in the oleic acid period (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Oleic acid modulates the partitioning of cholesterol from micellar bile salt solution.

The effects of monounsaturated fatty acid (oleic acid) on cholesterol monomer activity and on the rate of cholesterol influx were studied in vitro. A polyethylene disc method was employed to determine cholesterol monomer activity in constant sodium taurocholate-cholesterol micellar solution containing different oleic acid concentration levels at pH 5.5, 6.5 and 7.2. In addition, the effect of oleic acid on the rates of cholesterol influx was determined using an everted rat jejunal sac technique. At pH 5.5, increased oleic acid concentration from 5 to 10 mM resulted in significant decreased apparent cholesterol monomer activity (3.8 +/- 0.21 nmol/disc vs 1.0 +/- 0.08, P less than 0.001). At pH 6.5, apparent cholesterol monomer activity was 2.3 +/- 0.19 nmol/disc at 5 mM and 0.5 +/- 0.09 at 16 mM oleic acid level (P less than 0.001). Apparent monomer activity of cholesterol in micellar solutions at pH 7.2 used for the influx study at 5 and 15 mM oleic acid concentration level was 1.8 +/- 0.14 and 0.7 +/- 0.08 nmol/disc, respectively (P less than 0.001). Thus there was a significant decrease in cholesterol monomer activity by the addition of oleic acid at each pH. The rate of cholesterol influx across the brush border membrane of the rat jejunum at 5 and 15 mM oleic acid concentration level was 3.2 +/- 0.31 and 1.5 +/- 0.21 nmol/100 mg dry weight tissues/min, respectively (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Linoleic acid and oleic acid increase the endothelin-1 binding and action in cultured rat aortic smooth muscle cells.

An increase in circulating non-esterified fatty acids (NEFA) has been observed in patients with poorly controlled diabetes mellitus. To investigate whether fatty acids will affect the endothelin-1 (ET-1) receptor and thus contribute to the acceleration of atherosclerosis in diabetic patients, cultured rat aortic smooth muscle cells (SMC) were maintained in media containing higher (similar to those in diabetic patients) concentrations of oleic acid (OA) or linoleic acid (LA). The ET-1 binding and ET-1-stimulated thymidine uptake were then examined. We found that cells treated with OA (500 micromol/L) or LA (250 micromol/L) showed a significant increase in ET-1 receptor amount as demonstrated by Scatchard analysis (Bmax: 7.40 +/- 1.04 v 2.71 +/- 0.54 fmol/mg and 5.00 +/- 1.00 v 3.32 +/- 0.70 fmol/mg, respectively). No change in binding affinity was found. Moreover, both the basal and ET-1-stimulated thymidine uptake were enhanced by treatment with either LA (basal, 11,367 +/- 4,117 cpm/mg; LA, 13,933 +/- 4,003 cpm/mg; ET-1 (10(-8)), 16,931 +/- 4,412 cpm/mg; LA +/- ET-1 (10(-8)), 28,855 +/- 5,217 cpm/mg) or OA (basal, 4,912 +/- 1,193 cpm/mg, OA, 8,027 +/- 1,318 cpm/mg; ET-1 (10(-8)) 9,947 +/- 2,520 cpm/mg; OA + ET-1 (10(-8)), 16,761 +/- 1,740 cpm/mg). This enhancement in thymidine uptake was associated with an increase in cell number. Because ET-1 and its receptor are involved in atherogenesis, our findings suggested that increase in circulating NEFA may contribute to the acceleration of atherosclerosis in diabetic patients. Further studies to confirm its role in the vascular wall are warranted.

Animals↗

Central administration of oleic acid inhibits glucose production and food intake.

The hypothalamus and other regions within the central nervous system (CNS) link the sensing of nutrients to the control of metabolism and feeding behavior. Here, we report that intracerebroventricular (ICV) administration of the long-chain fatty acid oleic acid markedly inhibits glucose production and food intake. The anorectic effect of oleic acid was independent of leptin and was accompanied by a decrease in the hypothalamic expression of neuropeptide Y. The short-chain fatty acid octanoic acid failed to reproduce the metabolic effects of oleic acid, and ICV coadministration of inhibitors of ATP-sensitive K(+) channels blunted the effect of oleic acid on glucose production. This is the first demonstration that fatty acids can signal nutrient availability to the CNS, which in turn limits further delivery of nutrients to the circulation.

Adenosine Triphosphate↗

Acute intramuscular injection of oils or the oleic acid component protects mice against paraquat lethality.

Although selenium or vitamin E deficiencies or changing from cereal-based to purified diets augments paraquat toxicity, the action of other dietary components in normal animals fed nutritionally adequate diets is not clear. Upon injection of mice with antiinflammatory agents, a protective action of the corn oil vehicle against paraquat lethalities was noted. This preventive action of a large parenteral administration of unknown components in oils served as the basis for this study. Intramuscular injection of various vegetable oils protected similarly, indicating that in mixtures, the degree of lipid saturation did not seem to be an important factor. Injection of the monounsaturated fatty acid oleic acid decreased oral paraquat lethalities in mice, but linoleic, gamma-linoleic or linolenic acids were not protective in either male or female mice. Measurement of paraquat concentrations in various tissues at various times after administration indicated no effect of corn oil on paraquat distribution. Although the exact mechanism of the complex nature of oil protection against paraquat toxicity in mice is still unknown, this study provides evidence for in vivo oxidant protection by a monounsaturated fatty acid.

Animals↗

Association of meibum oleic acid with meibomian seborrhea.

PURPOSE: We sought to determine whether patient meibum fatty acid unsaturation is associated with meibomian gland secretion consistency. METHODS: Meibomian gland secretions were dissolved in chloroform and separated into lipid classes by thin-layer chromatography. Fatty acids in individual lipid classes were characterized by gas chromatography after transmethylation. RESULTS: Meibum from patients with meibomian seborrhea was higher, and meibum from patients with meibomian keratoconjunctivitis (meibomianitis) was lower in the monounsaturated fatty acid, oleic acid, than that of other disease groups and normal subjects. CONCLUSION: Our results strongly suggest that the melting characteristics of meibum, influenced primarily by the amount of oleic acid in wax and sterol esters and free fatty acids, greatly influence the consistency of meibomian gland secretions.

Blepharitis↗

Oleic acid uptake by in vitro English sparrow skeletal muscle.

Studies of prolonged avian flight have shown it to require large amounts of energy supplied mainly by free fatty acids (FFA). In the present study, the high levels of plasma ketone bodies found in sparrows (2.58 mmol l(-1)) are supportive of the use of fatty acids for flight. To determine the nature of fatty acid (oleic acid, OA) uptake, various pharmacological agents were used. The uptake of OA was examined using the extensor digitorum communis (EDC) muscle of English sparrows incubated in vitro. Initial studies demonstrated that radiolabeled OA uptake decreased in the presence of increasing unlabeled OA, suggesting that uptake occurred by a facilitative transport process. To further characterize OA uptake, EDC muscles were incubated with either: insulin (2 ng ml(-1)), insulin-like growth factor isoform-1 (IGF-I; 48 ng ml(-1)), 5'-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 2 mmol) or caffeine (5 mmol). Insulin, but not IGF-I, significantly increased OA uptake by avian EDC (P < 0.01). Caffeine and AICAR were ineffective at increasing OA uptake. A specific inhibitor of FFA transport by fatty acid transporters (FAT/CD36), sulfo-N-succinimidyl oleate (SSO; 500 micromoles), significantly decreased OA uptake at 2.5 min. The effectiveness of SSO suggests that a FAT/CD36-like protein is expressed in avian tissues. As uptake of OA was not completely blocked by SSO, it is likely that other mechanisms for FFA movement across membranes, such as diffusion, may be present.

Aminoimidazole Carboxamide↗