• Journal of Veterinary Clinics
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• v.21 no.4
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• pp.336-342
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• 2004

The immunoenhancing effect of CLA isomers (CLA mixture, 10t-12c CLA, 9c-11c CLA, 9c-11c CLA, and 9t-11t CLA) on phagocytic activity of porcine peripheral blood leukocytes was examined. The phagocytic activities of peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) were analyzed by a flow cytometry system. The direct treatments of CLA isomers have no effect on phagocytosis of PMN as well as PBMC composed of approximately 10% monocytes and 90% lymphocytes. However, the phagocytic activities of PMN and monocyterich fraction from PBMC were remarkably enhanced by culture supernatant from PBMC treated with CLA mixture, 10t-12c CLA and 9c-11t CLA but not 9c-11c CLA and 9t-11t CLA. The phagocytic activity of PBMC was not enhanced by culture supernatant from PBMC treated with all CLA isomers. These results indicated that CLA isomers such as CLA mixture, l0t -12c CLA and 9c-11t CLA have an enhancing effect on phagocytosis of PMN and monocytes, which may be mediated through active humoral substances produced by CLA-stimulated PBMC. This study suggested that CLA stimulates PBMC to elaborate soluble factor(s), which may be an important mechanism for the enhancement of phagocytosis in non-specific immunity.

• Journal of Life Science
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• v.27 no.8
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• pp.965-973
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• 2017

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid with conjugated double bonds at C9,C11 and C10,C12 positions. Of possible CLA isomers, a naturally occurring CLA isomer is c9,t11-CLA which is produced from linoleic acid by linoleate isomerase from various rumen and lactic bacteria, and mushroom mycelia. Meanwhile, synthetically prepared CLA contained an equal amount of c9,t11-CLA and t10,c12-CLA isomers, and other isomers as minor constituents. CLA was firstly mentioned in 1939 during the elaidinization reaction of linoleic acid. Thereafter, CLA was not an attractant to scientists because it was not scientifically interested any more. However, since the anticarcinogenic action was driven from 7,12-dimethylbenz[a]anthracene (DMBA)-induced mouse skin carcinogenesis in 1987, CLA-related researches were drastically elevated, resulting in approximately 6,100 research papers in literature, so far. CLA exhibited the significant biological activities: anticarcinogenic, antidiabetic, antihypertensive, antiatherosclerotic, body-fat reducing, antioxidative, antiinflammatory, testosterone producing and other activities. Interestingly, two major CLA isomers, c9,t11-CLA and t10,c12-CLA, exhibited different biological activities. Meanwhile, t,t-CLA isomers which is minor constituent of chemically synthesized CLA from linoleic acid exhibited more potent anticarcinogenic activity in carcinogen-induced animal models and cancer cell lines than other CLA isomrs. In the present review, the significant biological activities of CLA were discussed along with historical studies of CLA since 1939.

• Journal of Veterinary Clinics
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• v.20 no.1
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• pp.1-6
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• 2003

Immunoenhancing effects of conjugated linoleic acid (CLA) isomers (l0t-l2c CLA, 9c-11t CLA, CLA mixture, 9c-11c CLA and 9t-11t CLA) on chemotactic activity of porcine peripheral blood polymorphonuclear cells (PMN) were examined. The chemotactic activity of PMN was evaluated by a modified Boyden chamber assay. CLA isomers at higher concentration of 50 to 200$\mu$M exhibited a low viability of cells by trypan blue exclusion. CLA isomers were used at concentration of 20uM showing no cytotoxic effect and high cell viability. CLA isomers themselves were not active or slight chemotactic for PMN. But culture supernatant from mononuclear cells (MNC) treated with 10t-12c CLA, 9c-11t CLA and CLA mixture except for 9c-11c. CLA and 9t-11t CLA enhanced remarkably chemotactic activity or porcine PMN PMN migration by culture supernatant from MNC treated with CLA mixture was found to be true chemotaxis by checkboard assay. This migration was also induced by porcine recombinant interleukin (rIL)-8. PMN chemotaxis caused both culture supernatant from MNC treated with CLA mixture and porcine rIL-8 was inhibited in a dose-dependent manner by addition of anti-porcine IL-8 polyclonal antibody. Therefore, these results strongly suggested that CLA (10t-12c CLA, 9c-11t CLA and CLA mixture) could stimulate porcine MNC to release and IL-8 like chemotactic activity.

• Journal of Animal Science and Technology
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• v.49 no.1
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• pp.25-32
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• 2007

The current study was undertaken to determine the effect of conjugated linoleic acid(CLA) isomers, cis-9, cis-11(c9c11), cis-9, trans-11(c9t11), trans-9, trans-11(t9t11), trans-10, cis-12(t10c12) on differentiation of pig preadipocytes and myogenic satellite cells during culture. Cells were isolated from new born pigs. The t10c12 isomer decreased differentiation of pig preadipocytes(92%), but not that of myogenic cells. The t9t11 isomer decreased differentiation of preadipocytes(14%) and increased that of myogenic cells (26%). No other CLA isomers affected differentiation of preadipocytes or myogenic cells. The effects of CLA on proliferation of preadipocytes and myogenic cells were small, compared to the effects on differentiation. These results suggest that CLA isomers have different effects on differentiaton of pig preadipocytes and myogenic cells.

• Journal of Veterinary Clinics
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• v.20 no.1
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• pp.66-73
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• 2003

Numerous physiological effects are attributed to conjugated linoleic acid(CLA). The purpose of this study is to consider these effects with respect to the cis-9, trans-11 and trans-10, cis-12 CLA isomer. Both isomers are natural products. The c9,t11-CLA isomer is the principal dietary form of CLA, but the concentrations of this isomer and the t10,c12-CLA Isomer in dairy products or beef vary depending on the diet fed to cows or steers, respectively. The influence of dietary CLA isomers on the immune response was examined, body weight and weight ratio of organ to body of Balb/C mice. Mice were divided into four groups of 8 mice. Balb/C mice were fed the experimental diets supplemented with 1% CLA (c9,t11-CLA isomer : t10,c12-CLA isomer = 2:3) (Group 1), 1% CLA (c9,t11-CLA isomer t10,c12-CLA isomer : 1:1) (Group 2), 1% safflower oil (Group 3) or nothing (Control) for 3 weeks. After 3 weeks, serum, gut lumen lavage, fat, liver, spleen and thymus were taken. Measurement of total immunoglobulin were executed using sandwich ELISA. Serum levels of IgA and IgM showed that group fed with t10,c12-CLA isomer significantly were higher than group fed with c9,tl1-CLA isomer. In addition serum level of IgG showed that group fed with t10,c9-CLA isomer significantly were lower than group fed with c9,tl1-CLA isomer. However, no significantly differences were observed in the serum IgE and secretory IgA. Weight ratio of spleen to body showed no significant differences. In weight ratio of liver and thymus to body, tl0,c9-CLA isomer significantly were respectively higher than group fed with c9,t11-CLA isomer. In weight ratio of fat to body, tl0,c9-CLA isomer significantly were respectively lower than group fed with c9,tl1-CLA isomer. In conclusion, t10,c12-CLA isomer produced a situation favorable for immunopotentiative effect and body composition. But it should be protected against hepatomegaly induced lipid accumulation in liver.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.10
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• pp.1525-1538
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• 2007

Because of the increasing evidence of potential benefits of conjugated linoleic acid (CLA) on human health, there is a need to investigate its status in commercial dairies and develop feeding strategies to enhance the content and supply of CLA in milk and milk products. A two-year experiment was conducted to study the status of milk fat c-9, t-11 CLA on four selected commercial dairy farms in Utah (two) and Idaho (two), USA. Farms A and C grazed cows on pasture and supplemented with 7.0 kg/cow per day of their respective grain mixes during summer, while conserved forage and grain mix was fed during winter. Farm B fed a total mixed diet all year, with 10% of diet dry matter as fresh cut pasture during summer. Farm D had 1/3 of its cows grazed on pasture and supplemented with a total mixed diet during summer, while the rest were fed a total mixed diet. All cows in Farm D were fed a total mixed diet during winter. Farms A, B, C, and D had on average 80, 400, 150, and 500 milking cows, respectively, with Holstein or its crosses as the major breed. On a year-round basis, Farms A and C produced milk with 60% or more milk fat c-9, t-11 CLA and transvaccenic acid (TVA) contents than Farm B. Similarly, Farm D produced 30% or more c-9, t-11 CLA and TVA in milk than Farm B. Milk fat content of CLA and TVA was 150-200% more during summer compared with winter. Individual cows varied from 0.16 to 2.22% in milk fat c-9, t-11 CLA contents and 89% of the cows had c-9, t-11 CLA contents between 0.3 and 1.0% of milk fat. Individual cow variation was larger on Farms A and C compared with Farm D, with least variation on Farm B. Variation was larger in summer than in winter. The bulk tank milk c-9, t-11 CLA content varied from 0.27 to 1.35% of milk fat. Cows on Farms A and C produced similar or higher amounts of milk fat c-9, t-11 CLA on a daily basis even though their milk yield was lowest among the dairies. Concentration and supplies of c-9, t-11 CLA and TVA were highest from June through September and lowest from February through April, which should be the months for targeting improvement in the content and supply of milk fat c-9, t-11 CLA and TVA.

• Journal of Nutrition and Health
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• v.36 no.7
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• pp.661-666
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• 2003

The study was designed to compare the anti-carcinogenic effect of conjugated linoleic acid (CLA) isomers on colon carcinogenesis in 1,2-dimethylhydrazine (DMH)-treated rats by determining the levels of apoptosis, cell proliferation, eicosanoids and 1,2-diacylglycerol (DAG) in colonic mucosa. Sixty male Sprague Dawley rats were randomly divided into 3 groups depending on the types of CLA isomers, i.e. BT group (no CLA contained), CLA-C group (cis-9, trans11 isomer contained), and CLA- T group (trans-10, cis-12 isomer contained). The experimental diet was composed of protein at 20%, carbohydrate at 56.2%, and fat at 14.5% including 0.8% CLA isomers by weight. The experimental diet was fed for 14 weeks with the initiation of intramuscular injection of DMH, which was injected twice a week for 6 weeks to give total dose of l80mg per kg body weight. Two CLA isomers (c9t11 and t10c12) significantly increased the relative percentage of apoptosis but reduced cell proliferation in mucosal cell and also the levels of PGE$_2$, TXB$_2$, and DAG in colonic mucosa. However, there was no significant differences in anti-carcinogenic effect between c9t11 isomer and t10c12 isomer. Overall, colon carcinogenesis could be significantly inhibited by CLA isomers by increasing apoptosis and reducing cell proliferation, the levels of eicosanoids and DAG in colonic mucosa.

• Journal of Nutrition and Health
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• v.37 no.7
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• pp.533-539
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• 2004

It has been reported that CLA decreases fat deposition in vivo and in vitro experiments. Among CLA isomers, c9t11 and t10c12 have been shown to exert active biological activities. For example, t10c12 reduces body weight and increases lean body mass, whereas, c9t11 has little effect on body fattness. However, the underlying molecular mechanism for the anti-obesity action of CLA isomers are not well understood. The purpose of this study was to examine the effects of t10c12 and c9t11 on lipid accumulation, cell proliferation, cell death and the expression levels of Ucp genes which are proposed as targets for anti-obesity in 3T3-L1 preadipocytes. Isomers of CLA at 50$\mu$M were added into preadipocyte differentiation medium for 3, 6 and 9days. Control cells received only the vehicle in the differentiation medium. Cytochemical analyses for lipid accumulation, cell proliferation and apotosis were carried out to compare lipidogenesis and cellular activity. RT-PCR analysis of GAPDH, Ucp 2,3 and 4 were also performed to find any modulatory effects of CLA isomers on the metabolic genes. Lipid accumulation indicated by Oil Red-O staining was inhibited in CLA isomers as compared to the control. T10c12 isomer showed less lipidogenesis than c9t11 did. A decrease occurred in CLA isomers as shown by BrdU incorporation. Apotosis has occured at higher level in t10c12 when compared to that of t9c11. Ucp 2, 3 and 4 genes were also upregulated in CLA isomers. T10c12 showed higher level of Ucp gene expressions than the c9t11 did. The biological activities of CLA isomers were also found to be different during differentiation of 3T3-L1 preadipocytes, suggesting that different isomers may be active in certain stage of lipidogenesis. The results indicate that both c9t11 and t10c12 CLA isomers decrease lipidogenesis, inhibit cell proliferation, increase cell death and upregulate in Ucp gene expressions during 3T3-L1 preadipocyte differentiation. T10c12 isomer was more effective than c9t11 in overall anti-obesity activity.

• Journal of Nutrition and Health
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• v.37 no.9
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• pp.763-770
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• 2004

This study was designed to compare the anti-carcinogenic effect of conjugated linoleic acid isomers on tumor incidence, cell proliferation and the levels of thromboxane (TX) B$_2$, prostaglandin (PG) E$_2$ and 1,2-diacylglycerol (DAG), and the related enzyme expression of cyclooxygenase (COX)-2 and protein kinase C (PKC) in colonic mucosa of 1,2-dimethy- lhydrazine (DMH) -treated rats. One hundred eight male Sprague Dawley rats were randomly divided into 3 groups depending on the types of CLA isomers, i.e. control group (no CLA contained), c9t11 group (cis-9, trans-11 CLA contained), and t10c12 group (trans-10, cis-12 CLA contained). The experimental diet was composed of protein at 20%, carbohydrate at 56.2%, and fat at 14.5% including 1.0% CLA isomers by weight. The experimental diet was fed for 30 weeks with the initiation of intramuscular injection of DMH, which was injected twice a week for 6 weeks to give total dose of 180 mg per kg body weight. Two CLA isomers (c9, t11, t10, c12) significantly reduced tumor incidence and cell proliferation by reducing the protein expression of COX-2 and PKC, and the level of TXB$_2$, PGE$_2$, and DAG in colonic mucosa. However, there was no significant difference in anti-carcinogenic effect between c9t11-CLA and t10c12-CLA.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.6
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• pp.1126-1133
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• 2002

Conjugated linoleic acid (CLA) is a collective term for a class of positional and geometric conjugated dienoic isomers of linoleic acid (LA) and has anti-cancer activity in experimental animals. We have previously observed that an isomeric mixture of CLA and trans-10,cis-12 (t10c12) inhibited cell growth in a dose-dependent manner whereas LA and cis-9,trans-11 (c9t11) had no effect. The present study examined whether the CLA mixture and t10c12 induce apoptotic cell death. TSU-Prl cells were incubated for three days in serum-free medium in the absence or presence of individual fatty acids, and the DNA fragmentation assay was performed. Cells treated with the CLA mixture or t10c12 produced a distinct oligonucleosomal ladder with different sizes of DNA fragments, a typical characteristic of cells undergoing apoptosis. By contrast, LA and c9t11 had no effect. Western immunoblot analysis of total lysates revealed that t10c12 reduced anti-apoptotic, 26 kDa, Bcl-2 protein levels by 49$\pm$8% compared with controls, whereas this CLA isomer did not alter pro-apoptotic,21 kDa, Bax protein levels. These results suggest that growth inhibitory effect of the t10c12 CLA isomer may, at least in part, be attributed to Increased apoptotic death in TSU-Prl cells.