• 한국임상수의학회지
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• 제21권4호
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• pp.336-342
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• 2004

돼지 말초혈액 탐식세포(PMN 및 monocyte)의 탐식성에 있어서 CLA 이성체의 탐식증강 효과를 검토하였다. 탐식세포의 탐식석은 fowl cytomery로 분석하였으며 결과는 다음과 같다. 1. CLA 이성체(CLA mixture, 10t-12c CLA, 9c-11t CLA, 9c-11c CLA, 9t-11t CLA)를 직접 첨가하여 배양한 PMN과 PBMC 및 fowl cytometry cytograpy에서 세포크기에 의해 분획한 monocyte-rich fractiondpsms 탐식증강 효과가 없었다. 2. 각각의 CLA 이성체로 배양한 PBMN 배양상층액으로 PBMC의 탐식활성을 측정한 결과 증강효과는 관찰되지 않았다. 3. CLA 이성체로 배양한 PBMC 배양상층액 중 CLA mixture, 10t-12c CLA, 9c-11c CLA 처리군에서는 PMN과 monocyte-rich fraction의 탐식활성에 있어서 현저한 증강효과가 관찰되었다. 그러나, 말초혈액 탐식세포들은 9c-11c CLA와 9t-11t CLA로 배양한 PBMC 배양상층액에 의해서는 증강효과가 나타나지 않았다. 4. CLA 이성체로 배양한 PMN 배양상층액에 있어서는 PMN과 monocyte-rich fraction의 탐식성을 측정한 결과, 어느 경우에도 증강효과는 나타나지 않았다. 이상의 결과로부터 CLA 중 CLA mixture, 10t-12c CLA. 9c-11t CLA가 돼지 말초혈액 탐식세포에 대하여 탐식증강효과를 가지고 있으며 이러한 증강효과는 직접적이라기보다는 CLA에 의해 활성화된 단핵구세포에서 분비되는 탐식촉진인자를 함유한 가용성 물질에 의해 autocrine 또는 paracrine 양상으로 탐식세포에 작용하는 것으로 생각되었다.

• 생명과학회지
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• 제27권8호
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• pp.965-973
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• 2017

CLA는 탄소가 18개(C18)인 linoleic acid의 이중결합이 C9,C11; C10,C12 위치로 이동됨으로 생성되는 입체이성(c,c; c,t; t,c; t,t)체를 총괄적으로 일컷는 말이다. 이론적으로 가능한 이성체 중에서 c9,t11-CLA가 rumen bacteria, lactic bacteria, 버섯균 등의 linoleate isomerase에 의해 linoleic acid로부터 생합성된다. 그러나 linoleic acid를 알카리 이성화로 합성한 CLA에는 이론적으로 가능한 모든 CLA 이성체가 존재한다. 그 중 c9,t11-CLA와 t10,c12-CLA가 약 45%씩 동일량 존재한다. CLA가 1939 년 linoleic acid의 elaidinization 반응에서 처음으로 소개되었으나 그 이후에는 과학적인 이용가치가 없어 과학자들의 관심의 대상이 되지 않았다. 그러나 1987년에 CLA가 7,12-dimethylbenz[a]anthracene (DMBA)으로 유도한 mouse skin carcinogenesis에서 항암성이 있다는 보고 이후 CLA에 관한 연구는 급속도로 증가하여 현재까지 약 6,100 연구논문이 발표되었다. CLA와 c9,t11-CLA 및 t10,c12-CLA 이성체는 in vitro와 in vivo에서 항암성, 항당뇨성, 항혈압성, 항동맥경화성, 면역증강성, 항산화성, 체지방감소성, testosterone 생산성 등의 생물학적 기능이 갖는다고 밝혀졌다. 이들 생리활성에 c9,t11-CLA와 t10,c12-CLA가 in vitro와 in vivo에서 다른 활성을 보이고 있다. 특히, 합성 CLA에 소량 혼합되어 있는 t,t-CLA가 carcinogen으로 유도한 동물모델이나 암세포에서 다른 이성체 보다 강한 항암성을 보이는 결과는 앞으로 더 많은 연구의 대상이 될 것이다. 본 총설에서는 CLA 관련 연구가 시작된 1939년부터 현재까지의 CLA 연구 트렌드를 살펴보고 밝혀진 주요 기능성을 보고한다.

• 한국임상수의학회지
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• 제20권1호
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• pp.1-6
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• 2003

돼지 말초혈액 다형핵 백혈구(polymorphonuclear cell; PMN)의 유주성에 있어서 conjugated linoleic acid(CLA) 이성체(CLA mixture, 10t-12c CLA, 9c-11t CLA, 9c-11c CLA 및 9t-11t CLA)의 면역증강 효과를 검토하였다. PMN에 대한 유주성은 Boyden chamber 변법으로 측정하였다. CLA 이성체들을 고농도(50∼200μM)로 사용하였을 경우 말초혈액 단핵구 세포(mononuclear cell; MNC) 및 PMN의 cell viability가 감소되거나 세포가 사멸하였다. 따라서 cell viability가 높고 세포독성을 나타내지 않는 20μM 농도로 유주활성 실험을 하였다. CLA 이성체들은 돼지 말초혈액 PMN의 유주활성에 직접적인 효과는 없었다. CLA 이성체로 배양한 MNC의 배양상층액 중 CLA mixture, 10t-12c CLA 및 9c-11t CLA 처리군에서는 PMN의 유주활성이 현저하게 증강되었으나 9c-11c CLA 및 9t-11t CLA로 배양한 MNC 배양상층액에서는 PMN의 유주활성이 나타나지 않았다. 이러한 유주성 증강효과는 checkerboard assay를 실시한 결과 진성의 유주활성이었다. 유주성 인자인 porcine recombinant (pr) interleukin(IL)-8을 이용하여 돼지 PMN에 대한 유주성을 검토한 결과, pr IL-8에 의한 PMN의 유주활성은 CLA로 배양한 MNC 배양상층액에 의한 것과 동등한 활성을 보였다. 또한 CLA로 배양한 MNC 배양상층액의 PMN에 대한 유주성을 anti-pr IL-8pAb를 사용하여 중화반응을 실시한 결과, CLA mixture로 배양한 MNC 배양상층액에 의해 증가된 PMN의 유주활성은 anti-pr IL-8 pAb 첨가에 의해 억제되어, 본 유주활성은 MNC에서 분비되는 IL-8으로 인한 것임을 강하게 시사하였다. 이상의 결과로부터 CLA 중 CLA mixture, 10t-12c CLA 및 9c-11t CLA 이성체가 돼지 말초혈액 다형핵 백혈구의 유주활성에 증강효과를 가지고 있으며, 이러한 증강효과는 CLA로 자극된 MNC에 의해 생성되는 IL-8 인자에 의한 것임을 알 수 있었다.

• Journal of Animal Science and Technology
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• 제49권1호
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• pp.25-32
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• 2007

본 연구는 여러 CLA 이성체, 즉 cis-9, cis- 11(c9c11), cis-9, trans-11(c9t11), trans-9, trans-11 (t9t11) 및 trans-10, cis-12(t10c12)가 배양 중인 돼지 지방세포와 근육세포의 분화와 증식에 미치는 영향을 구명하고자 실시하였다. 세포는 신생자돈으로부터 분리했다. t10c12 이성체는 지방세포의 분화를 억제했는데(92%) 근육세포의 분화는 억제시키지 않았다. t9t11 이성체는 지방세포의 분화를 억제했는데(14%), 근육세포의 분화는 촉진시켰다(26%). 다른 CLA 이성체는 지방세포나 근육세포의 분화에 영향을 미치지 않았다. 그리고 CLA가 지방세포와 근육세포의 증식에 미치는 영향은 분화에 미치는 영향에 비해서 작았다. 위의 결과는 여러 CLA 이성체는 돼지 지방세포와 근육세포의 분화에 다른 영향을 미침을 나타낸다.

• 한국임상수의학회지
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• 제20권1호
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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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• 제20권10호
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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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• 제36권7호
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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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• 제37권7호
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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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• 제37권9호
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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.

• 한국식품영양과학회지
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• 제31권6호
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• pp.1126-1133
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• 2002

CLA 이성체 mixture와 trans-10,cis-12 CLA는 살아있는 TSU-Prl 세포 수를 감소시키는 반면 LA와 cis-9,trans-11 CLA는 세포 수에 아무런 효과가 없었다. 세포 수를 감소시키는 CLA 이성체 mixture와 tran-10, cis-12 CLA는 apoptotic cell death를 유도하는 것을 관찰하였고, 특히 trans-10,cis-12 CLA는 Bcl-2/Bax 비율을 감소시켰다. Trans-10,cis-12 CLA에 의해 Bax와 Bcl-2 mRNA의 수준이 변하지 않았으므로 이 지방산에 의한 Bcl-2의 변화는 mRNA 전사 후에 일어나는 단계에서 일어난다고 결론지을 수 있다. 이로써 CLA에 의한 세포증식 억제는 부분적으로 TSU-Prl 세포의 apoptosis를 유도함으로서 이루어지는 것이라 할 수 있다.