• 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.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 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.

• Journal of Veterinary Clinics
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• v.32 no.2
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• pp.135-140
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• 2015

Trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) has been shown to participate in the regulation of anti-inflammatory effects. The objectives of this study were to examine the effects of t10c12-CLA on reactive oxygen species (ROS) and nitric oxide (NO) production and nuclear factor-kappaB (NF-${\kappa}B$) activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and to determine whether these effects were associated with change of intracellular calcium ion ($Ca^{2+}$). ROS production was increased in LPS-stimulated RAW 264.7 cells, and this effect was suppressed by 1,2-bis-(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM), a calcium chelator. t10c12-CLA suppressed ROS production in LPS-stimulated RAW 264.7 cells, which was further more decreased by treatment with BAPTA/AM. These indicated that t10c12-CLA decreases $Ca^{2+}$-dependent ROS production in LPS-stimulated RAW 264.7 cells. Similarly, NF-${\kappa}B$ p65 DNA binding activity and NO production were decreased by treatment with either t10c12-CLA, BAPTA/AM, or t10c12-CLA and BAPTA/AM combination. However, there were no differences between t10c12-CLA and BAPTA/AM treatment in NO production of LPS-stimulated RAW 264.7 cells. These data indicate that t10c12-CLA inhibits the increases in ROS and NO production and the NF-${\kappa}B$ activation in LPS-stimulated condition. These results suggested that CLA exerts potent anti-inflammatory effects by suppression of LPS-induced ROS and NO production, and NF-${\kappa}B$ activationn via $Ca^{2+}$-dependent pathway.

• 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 Food Hygiene and Safety
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• v.22 no.3
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• pp.145-150
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• 2007

Conjugated linoleic acid (CLA) reduces fat deposition in several mammalian species. The proposed mechanisms for this effect are reduced preadipocyte proliferation and differentiation. The objective of this study was to investigate the inhibitory effects of diglyceride (DG), CLA, DG-CLA of proliferation and differentiation of 3T3-L1 preadipocytes. Cell viability was determined using WST-8 analysis and cell differentiation was determined by glycerol-3-phosphate dehydrogenase (GPDH) activity. Lipid accumulation in differentiating 3T3-L1 cells was measured by Oil red O staining. The proliferation of preconfluent 3T3-L1 cells by treatments of DG, CLA, and DG-CLA was reduced in a dose-dependent manner. CLA among them was the most effective in reduction of viable cells with increasing concentrations. Treatments of the DG, CLA, and DG-CLA at the concentration of $100{\cdot}\ddot{I}g/ml$ for 48h significantly inhibited differentiation of 3T3-L1 cells (p<0.05). In addition. cytoplasmic lipid accumulation during differentiation of the 3T3-L1 preadipocytes was also inhibited by treatments of the test solutions. DG-CLA was the most effective in the inhibition of differentiation and lipid accumulation in 3T3-L1 cells. These results indicate that the DG including CLA as fatty acids is more effective for anti-obesity than DG or CLA alone and that consumption of DG-CLA as a dietary oil may give a benefit for controlling overweight in humans.

• 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 Animal Science and Technology
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• v.46 no.4
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• pp.645-658
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• 2004

To investigate the effects of conjugated linoleic acid added diet feeding on CLA accumulation and quality characteristics of manufactured press ham using CLA accwnulated pork loin meat. The CLA used to add in diet was chemically synthesized by alkaline isomerization method with com oil. Pigs were divided into 5 treatment groups(4 pigs/group) and subjected to one of five treatment diets(0, 1.25% CLA for 2weeks, 2.5% CLA for 2weeks, 1.25% CLA for 4weeks and 2.5% CLA for 4weeks, CLA diets; total fed diets) before slaughter. Pork loin were collected from the animals(110kg body weight) slaughtering at the commercial slaughter house. Manufacture press ham using CLA accumulated pork loin meat were vacuum packaged and then stored during 1, 7, 14, 21 and 28 days at 4$^{\circ}C$. Samples were analyzed for general compositions, physico-chemical properties(pH, color, shear force value), TBARS. pH value of CLA treatment(T4) was increased significantly than that of oontrol(P<0.05). pH of control and CLA treatments were increased significantly as the storage period passed(P< 0.05). Crude fat content of CLA treatment groups was significantly higher than the control pork (P<0.05). Meat color(CIE $L^*$, $a^*$$b^*$