• Journal of Nutrition and Health
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• v.35 no.2
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• pp.192-200
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• 2002

Conjugated linoleic acid (CLA) is a collective term for positional and geometric isomers of octadecadienoic acid in which the double bonds are conjugated. CLA has anticancer activity in a variety of animal cancer models, and cis-9, trans-11 (c9t11) and trans-10, cis-12(t10c12) CLA are the most predominant isomers present in the synthetic preparations utilized in these animal studies. To compare the ability of c9t11, t10c12 and an isomeric mixture of CLA to inhibit TSU-Prl cell growth, cells were incubated in a serum-free medium with various concentrations of these fatty acids. The isomeric mixture inhibited cell growth in a dose-dependent manner (1-3 $\mu$M) with a 41 $\pm$ 1% inhibition observed at 3 $\mu$M concentration after 48 hours. T10c12 also inhibited cell proliferation in a dote-dependent manner, However, the efficacy and potency of this isomer was much greater than that of the isomeric mixture with a 49 $\pm$ 2% inhibition observed at 0.3 $\mu$M concentration after 48 hours. By contrast, c9t11 slightly increased cell proliferation. To determine whether the growth-inhibiting effect of CLA is related to the changes in production of insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) by these cells, serum-free conditioned media were collected. Immunoblot analysis of conditioned media using a monoclonal anti-IGF-II antibody showed that both the isomeric mixture and t10c12 inhibited secretion of both mature 7,500 Mr and higher Mr forms of pro IGF-II, whereas c9t11 had no effect. Ligand blot analysis with 125I-IGF-II revealed the presence of two types of IGFBPs : 24,000 Mr IGFBP-4 and 30,000 Mr IGFBP-6. The production of IGFBP-4 slightly decreased at the highest concentrations of the isomeric mixture and t10c12. These results indicate that CLA inhibits human prostate cancer cell growth, an effect largely due to the action of t10c12. The growth inhibition may result, at least in part, from decreased production of IGF-II and IGFBP-4 by these cells.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.134-140
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• 2015

Conjugated linoleic acids (CLA) are a family of isomers of linoleic acid. CLA increases growth arrest and apoptosis of human colorectal cancer cells through an isomer-specific manner. ATF3 belongs to the ATF/CREB family of transcription factors and is associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which t10, c12-CLA stimulates ATF3 expression and apoptosis in human colorectal cancer cells. t10, c12-CLA increased an apoptosis in human colorectal cancer cells in dose dependent manner. t10, c12-CLA induced ATF3 mRNA and luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by t10, c12-CLA is located between -147 and -1850 of ATF3 promoter. mRNA stability of ATF3 was not affected by t10, c12-CLA treatment. t10, c12-CLA increases $GSK3{\beta}$ expression and suppresses IGF-1-stimulated phosphorylation of Akt. The knockdown of ATF3 suppressed expression of $GSK3{\beta}$ and NAG-1 and PARP cleavage. The results suggest that t10, c12-CLA induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.2
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• pp.222-226
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• 2003

The effects of dietary sources of C18:2 n-6 or C18:3 n-3 fatty acids on the occurrence of conjugated linoleic acid (CLA) and time-dependent changes of free fatty acid fractions in rumen contents were investigated. Sheep (n=4) fitted with rumen fistula were used in a 44 Latin square design wxith each 14 d period. Sheep were fed one of four diets consisting of grass hay and concentrates in a ratio of 70:30. Dietary treatments were 100% concentrates (served as the control), and concentrates were replaced by safflower seed at 30% (SFS), safflower meal at 18% - safflower oil at 12% (SFO), and safflower meal at 18%-linseed oil at 12% (LNO). At the end of each experimental period, rumen contents from each sheep were collected before feeding and at 1, 3, 6 and 12 h after feeding. The levels of cis-9, trans-11 CLA in free fatty acid fraction were considerably increased in all treated groups relative to the control, but not significantly. The increase in cis-9, trans-11 CLA was slightly higher in SFS and SFO groups than group fed diet containing linseed oil. The level of cis-9, trans-11 CLA in free fatty acid fraction was reached to the maximum value at 1hr after feeding and, thereafter gradually decreased to near the value before feeding. The generation of trans-11 C18:1 was significantly higher in all treated groups than that of control. The level of trans-11 C18:1 was linearly increased after feeding of experimental diets, reaching the maximum value at 3 h. Feeding of diets containing polyunsaturated fats to sheep resulted in a marked increase in the levels of trans-11 C18:1 and a slight increase of CLA in free fatty acid fraction of rumen contents. Our results support that endogenous synthesis of CLA from trans-11 C18:1 may be involved the primary source of CLA in dairy product. (Asian-Aust.

• Food Science of Animal Resources
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• v.33 no.4
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• pp.487-492
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• 2013

The objective of this study was to examine the effect of supplementation of high linoleic ($C_{18:2}$) oil or high linolenic ($C_{18:3}$) oil to the diet on milking performance and content of conjugated linoleic acid (CLA) isomers in goat milk fat. Forty five dairy goats (Sumnen, 25 d post-partum, $62.5{\pm}1.2kg$) were randomly assigned to three treatment groups with each group of 15 dairy goats. The goats were fed a basal diet (CON) consisting 1.2 kg concentrate and 1.2 kg chopped hay (0.6 chopped alfalfa and 0.6 kg hay) daily with 4% soybean oil (SO) or 4% linseed oil (LO). Daily feed intake was not influenced (p>0.05) but daily milk yield (p<0.001) and milk fat yield (p<0.001) were significantly increased by supplementation of oils. Supplementation of oils decreased the short chain fatty acid, medium-chain fatty acid and saturated fatty acid in goat milk fat while increased trans vaccenic acid (trans-11-$C_{18:1}$, TVA), oleic acid ($C_{18:1}$), $C_{18:2}$, $C_{18:3}$, cis-9, trans-11-CLA (c9, t11-CLA), trans-10, cis- 12-conjugated linoleic acid (t10, c12-CLA), unsaturated fatty acids, mono unsaturated fatty acid and long-chain fatty acid in goat milk fat (p<0.001). Especially, c9, t11-CLA, t10, c12-CLA and ${\omega}-3$ fatty acid ($C_{18:3\;n-3}$) in milk fat were highest when goat fed LO diet. Based on the result, it is suggested that supplementation of linseed oil should be an effective method to increase CLA isomers and ${\omega}-3$ fatty acid in goat milk fat without negative effect on lactating performance.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.5
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• pp.679-683
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• 2006

A feeding trial was conducted with 10 sheep for 12 weeks to examine the effect of soybean oil (SBO) supplementation on long-chain fatty acids composition, especially cis9,trans11-conjugated linoleic acid (c9,t11-CLA) in fat tissues. Sheep were fed either a SBO supplemented diet (5%, DM basis) or a control diet without SBO. Chopped rye grass hay was fed as roughage. Concomitant increases in contents of total cholesterol (T-C) and HDL-cholesterol (HDL-C) in the plasma of sheep were observed from the SBO supplementation. The supplementation of SBO reduced (p<0.05) the proportions of $C_{16:1}$, $C_{17:0}$ and $C_{17:1}$ but increased (p<0.05) the proportions of $C_{18:0}$ and octadecenoic acid (t11-$C_{18:1}$) in the intramuscular fat. The $C_{18:0}$ proportion only in the subcutaneous fat was increased (p<0.05) by the SBO supplementation. The SBO supplementation slightly increased CLA proportion in the intramuscular fat and subcutaneous fat.

• Journal of Veterinary Clinics
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• v.31 no.6
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• pp.469-476
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• 2014

The aims of this study were to explore the effects of conjugated linoleic acid (CLA) on reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-naïve and LPS-stimulated RAW 264.7 macrophages and to examine whether these effects affect the regulation of tumor necrosis factor-alpha (TNF-${\alpha}$) production, and nuclear factor-kappa B (NF-${\kappa}B$) and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) activation. Trans-10, cis-12(t10c12)-CLA increased the production of ROS, as well as TNF-${\alpha}$ in LPS-naïve RAW 264.7 cells. The CLA-induced TNF-${\alpha}$ production was suppressed by treatment of diphenyleneiodonium chloride (DPI), a NADPH oxidase inhibitor. In addition, CLA enhanced the activities of NF-${\kappa}B$ and $PPAR{\gamma}$ in LPS-naïve RAW 264.7 cells, and this effect was abolished with DPI treatment. LPS treatment increased ROS production, whereas CLA reduced LPS-induced ROS production. LPS increased both TNF-${\alpha}$ production and NF-${\kappa}B$ activity, whereas t10c12-CLA reduced TNF-${\alpha}$ production and NF-${\kappa}B$ activity in LPS-stimulated RAW 264.7 cells. DPI treatment suppressed LPS-induced ROS production and NF-${\kappa}B$ activity. Moreover, DPI enhanced the inhibitory effects of t10c12-CLA on TNF-${\alpha}$ production and NF-${\kappa}B$ activation in LPS-stimulated RAW 264.7 cells. However, neither t10c12-CLA nor DPI affected $PPAR{\gamma}$ activity in LPS-stimulated RAW 264.7 cells. Taken together, these data indicate that t10c12-CLA induces TNF-${\alpha}$ production by increasing ROS production in LPS-naïve RAW 264.7 cells, which is mediated by the enhancement of NF-${\kappa}B$ activity via $PPAR{\gamma}$ activation. By contrast, t10c12-CLA suppresses TNF-${\alpha}$ production by inhibiting ROS production and NF-${\kappa}B$ activation via a $PPAR{\gamma}$-independent pathway in LPS-stimulated RAW 264.7 cells. These results suggest that t10c12-CLA can modulate TNF-${\alpha}$ production and NF-${\kappa}B$ activation through formation of ROS in RAW 264.7 macrophages.

• Proceedings of the Korean Nutrition Society Conference
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• 2003.10a
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• pp.173-173
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• 2003

• Korean Journal of Microbiology
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• v.51 no.3
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• pp.231-240
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• 2015

In this study, a total of 16 conjugated linoleic acid (CLA) producing lactic acid bacteria (LAB) were isolated from fermented foods. Among those strains, the S48 and P1201 strains were capable of producing higher CLA contents than other LABs. The two strains were classified as Lactobacillus plantarum based on morphological, physiological, chemotaxonomic, and molecular-genetic properties. The survival rates of these strain appeared to be 59.57% and 62.22% under artificial gastric conditions after 4 h at pH 2.5, respectively. These strains produced the cis-9, trans-11, and trans-10, cis-12 CLA isomers from 8% skim milk medium supplemented with the different free LA concentration at $37^{\circ}C$ for 48 h and the production of two CLA isomers constantly increased in the growth until 48 h of incubation. After 48 h of fermentation, the levels of CLA appeared highest in steamed soy-powder milk than fresh and roasted soy-powder milks. In particular, the CLA contents were produced $183.57{\mu}g/ml$ and $198.72{\mu}g/ml$ from steamed soy-powder milk after fermentation (48 h) with S48 and P1201 strains, respectively.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.12
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• pp.1728-1735
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• 2008

The present study was conducted with four ruminally canulated Holstein cows to observe the effects of monensin or fish oil on diet fermentation and production of conjugated linoleic acids (CLAs) in the rumen when fed diets supplemented with soybean oil and sodium bicarbonate. Cows of the control treatment were fed a basal diet (CON) consisting of 60% commercial concentrate and 40% chopped rye grass hay. Cows of other treatments were fed the same diet as CON, but the concentrate was supplemented with 7% of soybean oil and 0.5% of sodium bicarbonate (SO-B), SO-B supplemented with monensin (30 ppm, SO-BM) or concentrate supplemented with 6.3% of soybean oil, 0.5% of sodium-bicarbonate, 30 ppm of monensin and 0.7% of fish oil (SO-BMF). Dry matter (DM) intake of the cows was significantly (p<0.011) reduced by feeding the SO-BMF diet compared to the other diets which did not differ in DM intake. Whole tract digestibility of major dietary components was significantly (p<0.004-0.027) higher for SO-BMF than the other supplement-containing diets. Dietary supplements did not clearly affect rumen pH and ammonia concentrations compared to the CON diet. Significantly reduced (p<0.05) total VFA concentration was obtained by the addition of fish oil to the diet (SO-BMF) compared to other diets. No differences, however, were obtained in major VFA proportions as well as in total VFA between the supplemented diets. The SO-BM diet increased (p<0.01-0.05) the concentrations of trans-11 $C_{18:1}$ and linoleic acid in rumen fluid. Total CLA concentration was also increased by the feeding of SO-B and SO-BM diets during early fermentation times (up to 3 h) post-feeding. Cis-9, trans-11 CLA concentration in rumen fluid was highest (p<0.05) for SO-B up to 1 h while the highest (p<0.01) value for SO-BM occurred at 3 h post-feeding. An increased trans-10, cis-12 CLA concentration was obtained from the SO-B and SO-BM diets at 1 and 3 h post feeding compared to the other diets. Supplementation of oils with monensin and sodium bicarbonate increased (p<0.05) the proportions of $C_{18:1}$ and CLA in the plasma of cows, but the effect of monensin and/or fish oil was limited to trans-10, cis-12 CLA.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.7
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• pp.1031-1035
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• 2002

This study was carried out to obtain conjugated linoleic acid (CLA) producing lactic acid bacteria for further study on the enzymes related to the production of CLA which has gained considerable attention and on the development as a probiotic culture. Total 34 lactic acid bacteria were isolated from 19 feces samples of healthy babies. CLA forming ability was measured spectrophotometrically by the modification of linoleate 12-cis, 11-trans-isomerase activity measuring method, and CLA of the cultures were extracted, methylated, and examined by HPLC analysis. CLA methyl ester of only one culture showing the highest value of CLA forming ability could be detected by HPLC analysis. The culture was found to be Gram positive, rods and catalase negative. It grows at $45^{\circ}C$ but not at $15^{\circ}C$, and was identified to be Lactobacillus fermentum on the basis of the biochemical characteristics and the utilization of substrates. These results provide an efficient experimental method to screen CLA producing lactic acid bacteria.