• Preventive Nutrition and Food Science
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• 제11권1호
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• pp.1-5
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• 2006

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid that have been used to reduce the incidence, growth and metastasis of breast, colon, prostate and gastric cancer in animals. CLA could reduce tumor growth by altering angiogenesis; a process requiring associated angiogenic factors such as vascular endothelial growth factor (VEGF). In this study, we determined whether CLA could modulate the expression of VEGF in murine mammary tumor cells and adipocytes. The c9, t11-CLA isomer reduced VEGF transcripts and protein when mammary tumor cells were stimulated with PMA. That isomer also reduced VEGF expression in un stimulated mouse 3T3-L1 adipocytes. Since VEGF can be regulated by cyclooxygenase-2 (COX-2), we determined whether CLA could alter COX-2 enzyme expression and $PGE_2$ production. The c9, t11-CLA isomer reduced not only COX-2 enzyme expression but also $PGE_2$ production. Thus, c9, t11-CLA could modulate neovascularization by alteration of VEGF expression from mammary tumor cells and adipocytes by reducing COX-2 metabolites.

• Asian-Australasian Journal of Animal Sciences
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• 제20권9호
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• pp.1374-1388
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• 2007

Three experiments were conducted to investigate the hypothesis that cows grazing on pasture produce the highest proportion of c-9 t-11 CLA in milk fat and no further increase can be achieved through supplementation of diets rich in linoleic acid, such as full-fat extruded soybeans or soybean oil. In experiment 1, 18 lactating Holstein cows were used in a randomized complete block design with measurements made from wk 4 to 6 of the experiment. In experiment 2, three cannulated lactating Holstein cows were used in a $3{\times}3$ Latin square design. Each period was 4 wk with measurements made in the final wk of each period. Cows in both experiments were assigned at random to treatments: a, conventional total mixed ration (TMR); b, pasture (PS); or c, PS supplemented with 2.5 kg/cow per day of full-fat extruded soybeans (PES). In both experiments, feed intake, milk yield, milk composition, and fatty acid profile of milk and blood serum were measured, along with fatty acid composition of bacteria harvested from rumen digesta in experiment 2. In experiment 3, 10 cows which had continuously grazed a pasture for six weeks were assigned to two groups, with one group (n = 5) on pasture diet alone (PS) and the other group (n = 5) supplemented with 452 g of soy oil/cow per day for 7 d (OIL). In experiment 1, cows in PS treatment produced 350% more c-9, t-11 CLA compared with cows in TMR treatment (1.70 vs. 0.5% of fat), with no further increase for cows in PES treatment (1.50% of fat). Serum c-9, t-11 CLA increased by 233% in PS treatment compared with TMR treatment (0.21 vs. 0.09% of fat) with no further increase for cows in PES treatment (0.18% of fat). In experiment 2, cows in PS treatment produced 300% more c-9 t-11 CLA in their milk fat compared with cows in TMR treatment (1.77 vs. 0.59% of fat), but no further increase for cows in PES treatment (1.84% of fat) was observed. Serum c-9, t-11 CLA increased by 250% for cows in PS treatment compared with cows in TMR treatment (0.27 vs. 0.11% of fat), with no further increase for cows in PES treatment (0.31% of fat). The c-9, t-11 CLA content of ruminal bacteria for cows in PS treatment was 200% or more of TMR treatment, but no further increase in bacterial c-9, t-11 CLA for cows in PES treatment was observed. Supplementation of soy oil in experiment 3 also did not increase the c-9 t-11 CLA content of milk fat compared with cows fed a full pasture diet (1.60 vs. 1.54% of fat). Based on these findings, it was concluded that supplementing with feeds rich in linoleic acid, such as full-fat extruded soybeans or an equivalent amount of soy oil, to cows grazing perennial ryegrass pasture may not increase milk fat c-9 t-11 CLA contents.

• Asian-Australasian Journal of Animal Sciences
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• 제25권1호
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• pp.75-85
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• 2012

An experiment was conducted to compare the effect of the same amount of 18:2 offered either as 18:2n-6 or as a mixture of unprotected 18:2c9t11 and 18:2t10c12 on feed intake, milk components as well as plasma and milk fatty acid profile. Fifteen cows were blocked by milk yield and milk fat percentage and within block assigned randomly to 1 of 3 treatments (n = 5). Each cow passed a 12-d adjustment period (AP) on a basal diet. After the AP cows received 1 of 3 supplements during an 18-d experimental period (EP). The supplements contained either 1.0 kg ground sunflower seeds (S), 0.5 kg conjugated linoleic acid (CLA)-oil (C) or 0.75 kg of a mixture of ground sunflower seeds and CLA-oil (2:1; SC). All 3 supplements contained the same amount of 18:2 either as CLA (${\Sigma}18$:2c9t11+18:2t10c12, 1:1) or as 18:2c9c12. During the last 2 d of AP and the last 4 d of EP feed intake and milk yield were recorded daily and milk samples were collected at each milking. Blood samples were collected from the jugular vein on d 11 of AP and d 15 and 18 of EP. The 18:2 intake increased in all treatments from AP to EP. Regardless of the amount of supplemented CLA, the milk fat percentage decreased by 2.35 and 2.10%-units in treatment C and SC, respectively, whereas in the treatment S the decrease was with 0.99%-unit less pronounced. Thus, C and SC cows excreted daily a lower amount of milk fat than S cows. The concentration of trans 18:1 in the plasma and the milk increased from AP to EP and increased with increasing dietary CLA supply. While the concentration of 18:2c9t11 and 18:2t10c12 in the plasma and that of 18:2t10c12 in the milk paralleled dietary supply, the level of 18:2c9t11 in the milk was similar in C and CS but still lower in S. Although the dietary concentration of CLA was highest in treatment C, the partial replacement of CLA by sunflower seeds had a similar inhibitory effect on milk fat synthesis. Comparable 18:2c9t11 levels in the milk in both CLA treatments implies that this isomer is subjected to greater biohydrogenation with increasing supply than 18:2t10c12. The fact that unprotected 18:2t10c12 escaped biohydrogenation in sufficient amounts to affect milk fat synthesis reveals opportunities to develop feeding strategies where reduced milk fat production is desirable or required by the metabolic state of the cow.

• Journal of Nutrition and Health
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• 제34권8호
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• pp.896-904
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• 2001

Conjugated linoleic acid(CLA) is a group of positional and geometric isomers of linoleic acid(LA) and exhibits anticarcinogenic activity in multiple experimental animal models. Cis-9,trns-11(c9t11) and trans-10,cis-12(t10c12) CLA are the principal isomers found in foods. The present study was performed to determine whether CLA and the two isomers inhibits HT-29 cell proliferation and to assess whether such an effect was related to changes in secretion of eicosanoids. Cells were incubated in serum-free medium with various concentrations(0 to 20$\mu$M) of CLA or LA. CLA inhibited cell proliferation in a dose-dependent manner, with maximal inhibition(70 $\pm$ 1%) observed at 20$\mu$M concentration after 96 hours. However, LA had no effect at the same concentration range. To compare the ability of c9f11 and t10c12 to inhibit cell proliferation, cells were incubated with increasing concentrations(0 to 4$\mu$M) of these isomers. T10c12 inhibited cell proliferation in a dose-dependent manner. A 66 $\pm$ 2% decrease in cell number was observed within 96 hours after addition of 4$\mu$M t10c12. By contrast, c9t11 had no effect. The concentrations of CLA and the two isomers in the plasma membrane were increased when they were added to the incubation medium. However, they did not alter the levels of arachidonic acid in plasma membrane. To assess whether the proliferation inhibiting effect of CLA was related to changes in eicosanoid production, prostaglandin E$_2$(PGE$_2$) and leukotriene B$_4$(LTB$_4$) concentrations in conditioned media were estimated by a competitive enzyme immunoassay. Both CLA and t10c12 increased the production of materials reactive to PGE$_2$ and LTB$_4$ antibodies in a dose-dependent manner. By contrast, c9t11 had no effect. These results indicate that inhibition of HT-29 cell proliferation by CLA is attributed to the effect of the t10v12 isomer. The materials reactive to PGE$_2$ and LTB$_4$ antibodies may inhibit growth stimulatory effect of arachidonic acid-derived eicosanoids on HT-29 cell proliferation.

• 한국축산식품학회지
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• 제30권6호
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• pp.879-885
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• 2010

Conjugated linoleic acid (CLA) isomers are found naturally in foods, such as milk, milk products, beef and others, from biohydrogenation of vegetable oils. They are heterogenous group of isomers of linoleic acid in the family of polyunsaturated fatty acids. Among the isomers of linoleic acid cis9, trans11- CLA (c9, t11-CLA) and trans10, cis12- CLA (t10, c12-CLA) are found to be biologically active isomers. These biologically active isomers either individual or combined found to be health beneficial in various diseases, such as cancer, diabetes, obesity, and atherosclerosis, conclusive participation in physiological processes are necessary. This review focused on the current study of CLA in prevention of disease, such as cancer, diabetes and atherosclerosis, and their effective function in body fat reduction, improvement of bone and muscle mass at a cellular, clinical and systematic level.

• Asian-Australasian Journal of Animal Sciences
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• 제21권10호
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• pp.1466-1472
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• 2008

Variations in conjugated linoleic acid (CLA) concentrations in Holstein dairy cows milk, depending on feeding systems in different seasons was investigated. Milk samples were collected from Holstein dairy cows, which either grazed for whole days (WG), only daylight hours (TG), or were offered a total mixed ration (TMR) and experienced no grazing (NG), from April to December of 2005. In April, November and December, the cows in TG and WG treatments received grass silage and some concentrate, while from May to October, the cows grazed on temperate pasture. The cows in NG treatment received the TMR throughout the season. The major fatty acid obtained in the pastures was linolenic acid. There was no significant difference in the pasture's linolenic acid concentrations from May to September, but there was a significant decrease in October. However, the linolenic acid concentrations obtained in the pasture were always much higher than those obtained from the TMR. Linoleic acid was also the major fatty acid in the TMR, but these concentrations were higher in the TMR than in the pasture. There was no significant difference in milk cis9trans11CLA (c9t11CLA) concentrations between the three feeding systems while the cows were fed on conserved pasture in April, November and December. Although c9t11CLA concentrations were lower in the TMR, it was found that the cows which grazed in fresh pasture experienced significantly higher concentrations of c9t11CLA in their milk than those which received only TMR. It was also found that cows in the WG treatment experienced higher c9t11CLA concentrations than those in the TG treatment. In the WG and TG treatments, c9t11CLA concentrations were highest in June, after which, they gradually decreased (p<0.01) until October. For the NG treatment, there was no significant change in the concentrations of c9t11CLA (p>0.05) with season. Overall, trans11C18:1 and c9t11CLA were greatly influenced by season, with higher variation in the WG treatment than in the TG treatment and no variation in the NG treatment.

• Journal of Nutrition and Health
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• 제35권2호
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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.

• Food Science and Biotechnology
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• 제17권1호
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• pp.31-37
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• 2008

The distributions and content of geometrical isomers of conjugated linoleic acids (CLA) in dairy foods such as milk, yogurt, and cheese, produced or being sold in the Quebec province of Canada, were investigated by gas chromatographic analysis. The mean contents of total CLA (mg/g fat) were $5.06{\pm}0.74$ in 4 low-fat milk samples, $14.14{\pm}4.95$ in 6 yogurt samples, and $18.22{\pm}7.89$ in 5 natural ripened cheeses. Among the yogurt samples, YY contained the highest content of total CLA ($20.68{\pm}5.17\;mg/g$ fat). Among the cheese samples, Gruyere contained the highest amount of total CLA ($29.86{\pm}0.62$) as well as c-9,t-11 ($22.03{\pm}0.36\;mg/g$ fat), followed by Jarlsberg ($22.76{\pm}0.14$), Provolone ($16.42{\pm}0.52$), Cheddar ($13.83{\pm}0.81$), and Swiss ($8.23{\pm}1.11$). Based on the distribution ratios of CLA isomers in these dairy foods, the c-9,t-11 isomer appeared to be the major CLA isomer in both the low-fat milk ($89.87{\pm}2.39%$) and yogurt ($90.98{\pm}4.42%$). In the cheeses, however, the ratio of c-9,t-11 ($54.86{\pm}13.06%$) was slightly higher than that of c-10,c-12 ($40.81{\pm}13.40%$).

• Asian-Australasian Journal of Animal Sciences
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• 제19권5호
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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.

• 한국임상수의학회지
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• 제20권4호
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• pp.437-442
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• 2003

CLA를 급여시킨 돼지에 있어 말초 혈액 세포의 변화와 탐식세포의 탐식반응을 조사하였다. 100일령, 평균체 중 80kg인 거세 수퇘지에게 10t-l2c CLA와 CLA mixture를 각각 사료 중에 5% 첨가하여 총 4주간에 걸쳐 자유급여 시켰다. 급여 전 (0주), 급여 2주후, 4주후 그리고 급여 중지 후인 5주차에 각각 혈액세포 수치(PCV 백혈구수 및 백혈구 감별계산치)의 변화와 탐식세포의 탐식활성을 측정하였다. CLA의 급여 따른 PCV의 수치에 있어서는 아무런 변화가 없었다. 그러나 10t-l2c CLA 또는 CLA mixture가 함유된 사료를 급여한 돼지에 있어서 CLA를 급여하지 않은 돼지에 비해 백혈구수 특히 호중구 수가 현저히 증가하였다. 말초혈액 단핵구세포(mononuclear cells; MNC)와 다형핵백혈구(polymorphonuclear cells; PMN)의 탐식능를 유세포분석기로 분석한 결과, 10t-l2c CLA 또는 CLA mixture 급여와 상관없이 MNC와 단구세포들(monocyte-rich cells)의 탐식능에는 변화가 없었다. 그러나 PMN의 탐식 활성은 CLA 무급여 대조돼지들에 비해 CLA 급여군은 2주에서 5주차에 걸쳐 증가된 탐식능를 나타내었다. 이상의 결과로부터 돼지에 CLA 급여는 호중구수 증가와 호중구 탐식능 증가를 유도할 수 있음을 제시하였으며 향후 생체방어 증강을 위해 CLA를 임상적으로 투여할 수 있을 것으로 보인다.