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The aldehydic metabolites of linoleic acid are cytotoxic against human breast cancer cells.

The cytotoxic effect of aldehydic metabolites of linoleic acid, 13-oxo-tridecadienoic acids, on MCF-7 human breast cancer cells was investigated. The metabolites inhibited the growth of the cancer cells and the effect was dependent on both time of exposure and concentration of the metabolites; 50% growth inhibition occurred at approximately 55 and 33 microM, after 3- and 5-day incubations, respectively. The metabolites had greater cytotoxicity than parent linoleic acid or other polyunsaturated fatty acids tested. The antiproliferative effect was partially reversed by 10 microM of dithiothreitol suggesting that attack on thiol groups in cancer cells by highly reactive alpha, beta-unsaturated carbonyl moiety in the metabolites was responsible for the cytotoxic actions.

Aldehydes↗

Microencapsulation of linoleic acid with low- and high-molecular-weight components of soluble soybean polysaccharide and its oxidation process.

Soluble soybean polysaccharide (SSPS) was fractionated into its low- (LMW) and high-molecular-weight (HMW) components to test their antioxidative and emulsifying properties. Linoleic acid was emulsified with an aqueous solution of SSPS, HMW, a mixture of LMW or HMW with maltodextrin, or maltodextrin alone. The emulsions prepared with SSPS, HWM and the mixture of HMW with maltodextrin were stable. These emulsions were spay-dried to produce microcapsules. The encapsulated linoleic acid was oxidized at 37 degrees C and at various levels of relative humidity. Linoleic acid encapsulated with the mixture of LMW with maltodextrin or HMW was stable to oxidation, and this stability increased as the weight fraction of LMW in the mixture was increased. The LMW components also had high DPPH-radical scavenging activity. These results indicate that LMW played an important role in suppressing or retarding the oxidation of linoleic acid encapsulated with SSPS. The oxidative stability of linoleic acid encapsulated with a mixture of the LMW and HMW components was high at low and high relative humidity, but not at intermediate levels of relative humidity.

Adsorption↗

Metabolism of Linoleic Acid or Mevalonate and 6-Pentyl-alpha-Pyrone Biosynthesis by Trichoderma Species.

The understanding of the biosynthetic pathway of 6-pentyl-alpha-pyrone in Trichoderma species was achieved by using labelled linoleic acid or mevalonate as a tracer. Incubation of growing cultures of Trichoderma harzianum and T. viride with [U-C]linoleic acid or [5-C]sodium mevalonate revealed that both fungal strains were able to incorporate these labelled compounds (50 and 15%, respectively). Most intracellular radioactivity was found in the neutral lipid fraction. At the initial time of incubation, the radioactivity from [C]linoleic acid was incorporated into 6-pentyl-alpha-pyrone more rapidly than that from [C]mevalonate. No radioactivity incorporation was detected in 6-pentyl-alpha-pyrone when fungal cultures were incubated with [1-C]linoleic acid. These results suggested that beta-oxidation of linoleic acid was a probable main step in the biosynthetic pathway of 6-pentyl-alpha-pyrone in Trichoderma species.

Journal Article↗

Conjugated linoleic acid modulates hepatic lipid composition in mice.

Conjugated linoleic acid (CLA) is a chemoprotective fatty acid that inhibits mammary, colon, forestomach, and skin carcinogenesis in experimental animals. We hypothesize that the ubiquitous chemoprotective actions of dietary CLA in extrahepatic tissues are dependent upon its role in modulating fatty acid composition and metabolism in liver, the major organ for lipid metabolism. This study begins to evaluate the role of CLA in lipid metabolism by determining the modulation of fatty acid composition by CLA. Female SENCAR mice were fed semipurified diets containing 0.0% (Diet A), 0.5% (Diet B), 1.0% (Diet C), or 1.5% (Diet D) CLA (by weight) for six weeks. Mice fed Diets B, C, and D exhibited lower body weights and elevated amounts of extractable total lipid in livers compared with mice fed diets without CLA (Diet A). Analyses of the fatty acid composition of liver by gas chromatography revealed that dietary CLA was incorporated into neutral and phospholipids at the expense of linoleate in Diets B, C, and D; oleate increased and arachidonate decreased in neutral lipids of CLA diet groups. In addition, increasing dietary CLA was associated with reduced linoleate in hepatic phospholipids. In an in vitro assay, CLA was desaturated to an unidentified 18:3 product to a similar extent as linoleate conversion to gamma-linolenate (9.88, and 13.63%, respectively). These data suggest that CLA may affect metabolic interconversion of fatty acids in liver that may ultimately result in modified fatty acid composition and arachidonate-derived eicosanoid production in extrahepatic tissues. In addition to determining how dietary CLA modulates eicosanoid synthesis, further work is needed to identify enzymatic products that may result from desaturation of CLA.

Animal Feed↗

Vitamin E in foods from high and low linoleic acid diets.

As part of a human diet study, vitamin E activity was estimated in foods used in seven daily menus. Each menu was designed to contain 35% fat calories with either 10 or 30 gm/day of linoleic acid (18:2) and 500 mg/day of cholesterol. To estimate vitamin E activity, each food used in the menus was analyzed for alpha and gamma tocopherol content by high-pressure liquid chromatography with fluorescence detection. This article reports the alpha and gamma tocopherol contents of those foods, tocopherol contributions from each food in one sample 2,400-kcal menu, and the mean daily vitamin E activity (milligram alpha tocopherol equivalents) of all seven menus at five caloric levels. Major sources of alpha tocopherol (greater than 10% of the RDA) common to both diets (10 and 30 gm linoleic acid) were olive oil and a few fruits and vegetables. Additional major sources in the 30-gm linoleic acid diets were polyunsaturated fatty acid (PUFA) vegetable oils and margarine. Contrary to a common assumption, increasing the level of PUFA in the menus did not necessarily result in higher milligram equivalents of alpha tocopherol because soybean oil, with a tocopherol composition that is predominantly gamma tocopherol, was the major source of linoleic acid in the diets. Thus, vitamin E activity was not necessarily increased when soybean oil was substituted for a less saturated fat such as olive oil, which has mostly alpha tocopherol.

Chromatography, High Pressure Liquid↗

Liver microsomal delta 6 and delta 5 linoleic acid desaturation in female BB rats.

Rat liver microsomal delta 6 and delta 5 desaturation are defective in experimental diabetes, but this defect is correctable with insulin treatment. Rat liver fatty acid composition and delta 6 and delta 5 desaturation were studied in the spontaneously diabetic adult female Bio-Breeding (BB) rat. Control Wistar rats and BB rats (4 weeks of diabetes), that received insulin (1 IU.100 g body weight-1.day-1), were killed 20 h after the last insulin injection. delta 6 and delta 5 desaturase activities were estimated from the incubation of liver microsomes with (1-14C) 18:2, n-6 or (2-14C) 20:3, n-6, respectively, and the fatty acid composition of the liver and microsomal liver lipids were investigated. Under experimental conditions delta 6 and delta 5 desaturase activities were unchanged in the BB rats when compared to the control rats. Impairment of the liver fatty acid composition of diabetic BB rats is not consistent with normal desaturase activity and may be explained by factors other than desaturation disturbance.

Animals↗

Linoleic acid esterified in low density lipoprotein serves as substrate for increased arachidonic acid synthesis in differentiating monocytic cells.

The cellular metabolism of albumin- and lipoprotein-bound 18:2(n - 6) during monocytic differentiation was examined in the human premonocytic U937 and Mono Mac 6 cells. Differentiation for 72 h of U937 cells with retinoic acid (RA, 1 microM) or 1,25-(OH)2-vitamin D3 (1,25-D3, 10 nM) and of Mono Mac 6 cells with RA (1 microM) or lipopolysaccharide (LPS, 10 ng/ml) increased the desaturation and elongation of [1-14C]18:2(n - 6) to [1-14C]20:4(n - 6). In undifferentiated U937 and Mono Mac 6 cells, incubations with human LDL (100 micrograms/ml, 18 h) resulted in a 2.5-fold increase in 18:2(n - 6) levels in the cellular phospholipids. Differentiation of U937 cells with RA or or of Mono Mac 6 cells with LPS prior to LDL addition. Significantly reduced 18:2(n - 6) and elevated 20:4(n - 6) levels in cellular phospholipids. This increase in 20:4(n - 6) was likely not due to an increased incorporation of preformed 20:4(n - 6) esterified in LDL, as the receptor-specific degradation of [125I]LDL was reduced in both the RA-treated U937 and LPS-treated Mono Mac 6 cells. In U937 cells incubated with [1-14C]18:2(n - 6), the synthesis of TXB2, PGE2 and HHT could be detected after differentiation with RA. suggesting the availability of [1-14C]20:4(n - 6), derived from [1-14C]18:2(n - 6), for cyclooxygenase metabolism. Our results show that the conversion of 18:2(n - 6) to 20:4(n - 6) increases during monocyte differentiation. The 18:2(n - 6) supplied to the cells via the receptor-mediated uptake of LDL was utilized as substrate for the increased 20:4(n - 6) synthesis.

Arachidonic Acid↗

Dietary conjugated linoleic acid modulation of phorbol ester skin tumor promotion.

The fatty acid derivative conjugated dienoic linoleate (CLA) has been shown to inhibit initiation and postinitiation stages of carcinogenesis in several experimental animal models. The goal of the present study was to determine the role of increasing levels of dietary CLA in mouse skin tumor promotion elicited by 12-O-tetradecanoylphorbol-13-acetate (TPA). Mice were fed control (no CLA) diet during initiation, then switched to diets containing 0.0%, 0.5%, 1.0%, or 1.5% (wt/wt) CLA during skin tumor promotion by TPA. Body weights of mice fed 0.5%, 1.0%, or 1.5% CLA were similar to each other but were significantly lower (p < 0.05) than weights of mice fed no CLA (0.0%) throughout promotion. A reduction in papilloma incidence was observed in mice fed 1.5% CLA from Weeks 8 to 24 compared with mice fed diets containing 0.0-1.0% CLA (p < 0.05). Twenty-four weeks after tumor promotion was begun, diets containing 1.0% and 1.5% CLA inhibited tumor yield (4.94 and 4.35 tumors/mouse, respectively) compared with diets without CLA (0.0% CLA, 6.65 tumors/mouse, p < 0.05) or 0.5% CLA (5.92 tumors/mouse, p < 0.05). These data indicate that CLA inhibits tumor promotion in a manner that is independent of its anti-initiator activity. Further studies are warranted in identifying cellular mechanisms that are likely to be involved with the antipromoter effects of CLA.

Animals↗

[Changes in the fatty acid composition of erythrocyte membranes in patients with chronic alcoholism under the effect of a diet enriched with linoleic acid].

The authors have studied the influence of additional introduction into the ration of sunflower oil on fatty-acid composition of erythrocytic membranes in chronic alcoholics. The computerized discriminant analysis has evidenced that additional introduction of sunflower oil into the ration of the patients normalizes the fatty-acid spectrum of erythrocytic membranes. Besides that, enrichment of the ration with linoleic acid improves the parameters characterizing the liver function (bilirubin, alanine aminotransferase of blood serum).

Adult↗

[Linoleic acid synthesis in oleaginous seeds].

Fats are synthetized in oleaginous seeds according to the following diagram: lipid synthesis, very slow immediately after fecundation, becomes very intensive between the second and the fifth weeks after florescence and is reduced to zero at the end of maturation. The desaturating activity of ammonium oleate is important in the first stages of development of the seeds.

Fatty Acids↗

Conjugated linoleic acid reduces arachidonic acid content and PGE2 synthesis in murine keratinocytes.

Dietary conjugated linoleic acid (CLA) is associated with decreased 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced tumor promotion in mouse skin. In addition, CLA decreases TPA-induced prostaglandin E synthesis and ornithine decarboxylase activity in cultured keratinocytes compared with linoleic acid (LA) and arachidonic acid (AA). When LA or CLA was added to keratinocyte cell cultures, the amounts of each of these cellular fatty acids increased significantly in a dose-dependent manner. Furthermore, LA treatment was associated with increased cellular AA while the AA content of keratinocytes was reduced when cultures were treated with CLA. Moreover, CLA (16 microg/ml) was more potent than LA at decreasing the level of 14C-AA incorporated into cellular phosphatidylcholine. In order to determine the effect of CLA on arachidonate-derived PGE2, the release of 14C-AA and 14C-PGE2 synthesis was measured in cultures pre-treated with LA/14C-AA or CLA/14C-AA for 12 h. The amount of 14C-AA release induced by TPA in CLA/14C-AA pre-treated cultures was significantly lower than cultures pre-treated with LA/14C-AA. Furthermore, TPA-induced 14C-PGE2 was significantly lower in cultures pre-treated with CLA/14C-AA compared with cultures pre-treated with LA/14C-AA. The effects of LA and CLA on AA composition of phospholipids and subsequent arachidonate-derived PGE2 synthesis will provide insight into the anti-promoter mechanisms of CLA.

Animals↗