Isomers of conjugated linoleic acid differ in their effects on angiogenesis and survival of mouse mammary adipose vasculature

Dietary conjugated linoleic acid (CLA) is a cancer chemopreventive agent that has been shown to inhibit angiogenesis in vivo and in vitro, and to decrease vascular endothelial growth factor (VEGF) and Flk-1 concentrations in the mouse mammary gland. To determine which isomer mediates the antiangiogenic effects of CLA in vivo, the effects of diets supplemented with 5 or 10 g/kg c9,t11- or t10,c12-CLA isomers were compared in CD2F1Cr mice. Both isomers inhibited functional vascularization of a matrigel pellet in vivo and decreased serum VEGF concentrations; the t10,c12 isomer also decreased the proangiogenic hormone leptin (P < 0.05). Additionally, the t10,c12 isomer, but not c9,t11-CLA, rapidly induced apoptosis of the white and brown adipocytes as well as the preexisting supporting vasculature of the mammary fat pad (P < 0.05). Independent of this isomer-specific adipose apoptotic effect, both isomers induced a rapid and reversible decrease in the diameter of the unilocular adipocytes (P < 0.05). The ability of both CLA isomers to inhibit angiogenesis in vivo may contribute to their ability to inhibit carcinogenesis. Moreover, we propose that each CLA isomer uniquely modifies the mammary stromal "soil" in a manner that is useful for chemoprevention of breast cancer.     

Effect of dietary conjugated linoleic acid isomers on lipid metabolism in hamsters fed high-carbohydrate and high-fat diets

Dietary conjugated linoleic acids (CLA) have been reported to have a number of isomer-dependent effects on lipid metabolism including reduction in adipose tissue deposition, changes in plasma lipoprotein concentrations and hepatic lipid accumulation. The aim of this study was to compare the effect of individual CLA isomers against lipogenic and high 'Western' fat background diets. Golden Syrian hamsters were fed a high-carbohydrate rodent chow or chow supplemented with 17.25 % fat formulated to represent the type and amount of fatty acids found in a typical 'Western' diet (including 0.2 % cholesterol). Diets were further supplemented with 0.25 % (w/w) rapeseed oil, cis9, trans11 (c9,t11)-CLA or trans10, cis12 (t10,c12)-CLA. Neither isomer had a significant impact on plasma lipid or lipoprotein concentrations. The t10,c12-CLA isomer significantly reduced perirenal adipose tissue depot mass. While adipose tissue acetyl CoA carboxylase and fatty acid synthase mRNA concentrations (as measured by quantitative PCR) were unaffected by CLA, lipoprotein lipase mRNA was specifically reduced by t10,c12-CLA, on both background diets (P < 0.001). This was associated with a specific reduction of sterol regulatory element binding protein 1c expression in perirenal adipose tissue (P = 0.018). The isomers appear to have divergent effects on liver TAG content with c9,t11-CLA producing lower concentrations than t10,c12-CLA. We conclude that t10,c12-CLA modestly reduces adipose tissue deposition in the Golden Syrian hamster independently of background diet and this may possibly result from reduced uptake of lipoprotein fatty acids, as a consequence of reduced lipoprotein lipase gene expression.     

Conjugated linoleic acid isomers and trans fatty acids inhibit fatty acid transport in hepatoma 7288CTC and inguinal fat pads in Buffalo rats

Conjugated linoleic acid (CLA) and some trans fatty acids (FA) decrease tumor growth and alter tumor and host lipid uptake and storage. The goal of this study was to test the hypothesis that the acute inhibitory effects of CLA isomers and trans FAs on FA transport in tumors and white adipose tissue are mediated via an inhibitory G-protein coupled (GPC), FFA receptor (FFAR). Experiments were performed in hepatoma 7288CTC and inguinal fat pads in Buffalo rats during perfusion in situ. CLA isomers and trans FAs (0.03-0.4 mmol/L, in plasma) were added to the arterial blood, and FA uptake or release was measured by arterial minus venous difference. In hepatoma 7288CTC, the CLA isomers, t10,c12-CLA > (+/-)-9-HODE [13-(S)-hydroxyoctadecadienoic acid] > t9,t11-CLA, and the trans FAs, linolelaidic = vaccenic > elaidic, decreased cAMP content and inhibited FA uptake, 13(S)-HODE release, extracellular signal-regulated kinase p44/p42 phosphorylation, and [(3)H]thymidine incorporation. Other CLA isomers, c9,t11-CLA, 13-(S)-HODE, c9,c11-CLA, and c11,t13-CLA, had no effect. In inguinal fat pads, FA transport was inhibited by t10,c12-CLA = linolelaidic acid > trans vaccenic acid, whereas c9,t11-CLA had no effect. In both hepatoma 7288CTC and inguinal fat pad, addition of either pertussis toxin or 8-Br-cAMP to the arterial blood reversed the inhibitions of FA transport. These results support the idea that an inhibitory GPC FFAR reduces cAMP and controls FA transport by CLA isomers and trans FAs. Ligand activity is conferred by the presence of a trans double bond proximal to the carboxyl group.     

Trans10,cis12-18:2 is a more potent inhibitor of de novo fatty acid synthesis and desaturation than cis9,trans11-18:2 in the mammary gland of lactating mice

To investigate the effects of 2 conjugated linoleic acid (CLA) isomers and trans11-18:1 (TVA) on de novo lipogenesis and desaturation in liver and mammary gland, lactating mice were fed diets containing 3% canola oil (control) or 2% canola oil plus 1% stearic acid (SA), TVA, cis9,trans11 CLA (c9t11), or trans10,cis12 CLA (t10c12). In mammary tissue, TVA and CLA isomers reduced mRNA for acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) compared with control, but only c9t11 and t10c12 reduced mammary ACC activity. Of the 2 CLA isomers, t10c12 caused a greater reduction in mammary ACC activity. Hepatic ACC or FAS activity and mRNA abundance were not affected by dietary treatments. Feeding TVA, c9t11, or t10c12 reduced mammary stearoyl-CoA desaturase 1 (SCD) mRNA and activity. Reduction was greater due to feeding t10c12 compared with c9t11. Hepatic SCD mRNA was not affected by dietary treatments, but both CLA isomers depressed hepatic SCD activity. Results indicated that t10c12 is a more potent inhibitor of mammary lipogenesis and desaturation than is c9t11. A net gain of 77 and 1690 micro g of c9t11 in liver and mammary tissue, respectively, was found in the TVA-fed group over the control and SA-fed group. However, reduced mammary SCD mRNA or activity due to feeding TVA may indicate a limited capacity for desaturation of dietary TVA to c9t11 in vivo.     

The conjugated linoleic acid (CLA) isomer,t10c12-CLA,is inversely associated with changes in body weight and serum leptin in subjects with type 2 diabetes mellitus

Isomers of conjugated linoleic acid (CLA) are found in beef, lamb and dairy products. Diets containing CLA reduce adipose mass in various depots of experimental animals. In addition, CLA delays the onset of diabetes in the ZDF rat model for obesity-linked type 2 diabetes mellitus. We hypothesize that there would be an inverse association of CLA with body weight and serum leptin in subjects with type 2 diabetes mellitus. In this double-blind study, subjects with type 2 diabetes mellitus were randomized into one of two groups receiving either a supplement containing mixed CLA isomers (CLA-mix; 8.0 g daily, 76% pure CLA; n = 12) or a supplement containing safflower oil (placebo; 8.0 g daily safflower oil, n = 9) for 8 wk. The isomers of CLA in the CLA-mix supplement were primarily c9t11-CLA ( approximately 37%) and t10c12-CLA ( approximately 39%) in free fatty acid form. Plasma levels of CLA were inversely associated with body weight (P < 0.05) and serum leptin levels (P < 0.05). When levels of plasma t10c12-CLA isomer were correlated with changes in body weight or serum leptin, t10c12-CLA, but not c9t11-CLA, was inversely associated with body weights (P < 0.05) and serum leptin (P < 0.02). These findings strongly suggest that the t10c12-CLA isomer may be the bioactive isomer of CLA to influence the body weight changes observed in subjects with type 2 diabetes. Future studies are needed to determine a causal relationship, if any, of t10c12-CLA or c9t11-CLA to modulate body weight and composition in subjects with type 2 diabetes. Furthermore, determining the ability of CLA isomers to influence glucose and lipid metabolism as well as markers of insulin sensitivity is imperative to understanding the role of CLA to aid in the management of type 2 diabetes and other related conditions of insulin resistance.     

Isomer-specific effects of conjugated linoleic acid on blood pressure, adipocyte size and function

Obesity-related hypertension may be caused by activation of the local adipose tissue renin-angiotensin system, resulting in exaggerated production of the vasoconstrictor angiotensin II. Additionally, secretion of adiponectin from adipose tissue, which prevents endothelial dysfunction, is altered in obesity. Consumption of conjugated linoleic acid (CLA) has been shown to modulate cytokine release from adipocytes and positively influence blood pressure in younger rats, but its physiological actions in older models with established hypertension and isomer-specific effects on adipocyte size remain to be determined. Therefore, we investigated the effects of CLA isomers on adipocyte size in relation to blood pressure and adipokine production by hypertrophic adipocytes in older fa/fa Zucker rats with established hypertension. fa/fa Zucker rats were fed with cis(c)9, trans(t)11-CLA or t10, c12-CLA isomers for 8 weeks and compared with lean and obese rats fed with the control diet. Blood pressure and adipocyte size were subsequently measured. Collagenase-isolated adipocytes were size-separated and angiotensinogen and adiponectin protein levels quantified by Western blotting. The t10, c12-CLA group had reduced blood pressure, fewer large adipocytes and increased serum adiponectin. Angiotensinogen was present at higher levels in the large adipocytes, whereas the converse was observed for adiponectin. The beneficial effects of the t10, c12-CLA isomer on blood pressure and adipocyte size in vivo may be due to its ability to reduce the number of large adipocytes, which alters the levels of vasoactive molecules secreted from adipose tissue.     

Conjugated linoleic acid-enriched butter fat alters mammary gland morphogenesis and reduces cancer risk in rats

Conjugated linoleic acid (CLA) is a potent cancer preventive agent in animal models. To date, all of the in vivo work with CLA has been done with a commercial free fatty acid preparation containing a mixture of c9,t11-, t10,c12- and c11,t13-isomers, although CLA in food is predominantly (80-90%) the c9,t11-isomer present in triacylglycerols. The objective of this study was to determine whether a high CLA butter fat has biological activities similar to those of the mixture of free fatty acid CLA isomers. The following four different endpoints were evaluated in rat mammary gland: 1) digitized image analysis of epithelial mass in mammary whole mount; 2) terminal end bud (TEB) density; 3) proliferative activity of TEB cells as determined by proliferating cell nuclear antigen immunohistochemistry; and 4) mammary cancer prevention bioassay in the methylnitrosourea model. It should be noted that TEB cells are the target cells for mammary chemical carcinogenesis. Feeding butter fat CLA to rats during the time of pubescent mammary gland development reduced mammary epithelial mass by 22%, decreased the size of the TEB population by 30%, suppressed the proliferation of TEB cells by 30% and inhibited mammary tumor yield by 53% (P < 0.05). Furthermore, all of the above variables responded with the same magnitude of change to both butter fat CLA and the mixture of CLA isomers at the level of CLA (0.8%) present in the diet. Interestingly, there appeared to be some selectivity in the uptake or incorporation of c9,t11-CLA over t10,c12-CLA in the tissues of rats given the mixture of CLA isomers. Rats consuming the CLA-enriched butter fat also consistently accumulated more total CLA in the mammary gland and other tissues (four- to sixfold increases) compared with those consuming free fatty acid CLA (threefold increases) at the same dietary level of intake. We hypothesize that the availability of vaccenic acid (t11-18:1) in butter fat may serve as the precursor for the endogenous synthesis of CLA via the Delta9-desaturase reaction. Further studies will be conducted to investigate other attributes of this novel dairy product.     

Dietary purified cis-9,trans-11 conjugated linoleic acid isomer has anticarcinogenic properties in chemically induced mammary tumors in rats

To determine whether the purified 9c,11t conjugated linoleic acid (CLA) isomer, the main dietary isomer, is biologically active on mammary tumor growth, we carried out a dietary intervention study designed to compare its effects with those of a mixture of CLA isomers on the incidence and growth of autochthonous mammary tumors induced by methylnitrosourea in rats. After the initiation step, rats were fed a sunflower oil-based diet (5%) and separated into three experimental groups supplemented with either a 1% homemade synthesized 9c,11t isomer, a 1% CLA isomer mixture, or free fatty acids prepared from sunflower oil for the control group. We found that, in the two CLA groups compared with the control group, CLA levels were about 30 times higher in mammary fat pads and about 10 times higher in tumor tissues. Compared with the control group, there was a 44% and 45% decrease in tumor mass per rat in the CLA mixture and the 9c,11t groups, respectively, at 20 wk of diet (P < 0.05). There was a nonsignificant trend for a decrease multiplicity in CLA groups compared with the control group, with a 30% and 35% decrease in the CLA mixture and the 9c,11t groups, respectively. Incidence and latency were not significantly different between the dietary groups. Although the effect was specifically restricted in reduction in tumor mass, we concluded that the main CLA isomer found in human diet has anticarcinogenic properties in experimental mammary carcinogenesis.     

Incorporation of conjugated linoleic acid isomers into porcine erythrocytes

Purpose

The aim of the current study was to determine the incorporation of cis (c) 9, trans (t) 11-conjugated linoleic acid (CLA) and t10, c12-CLA into porcine erythrocytes—both isomers were supplemented in equal proportions.

Methods

The study group consisted of 16 piglets randomly assigned into experimental and control group. For the period of 5 weeks, the piglets from the experimental group were receiving a 1.2 % CLA supplement while the controls were supplemented with the same amount of sunflower oil. For the remaining 7 weeks, the piglets were fed without a supplement. Blood samples to evaluate incorporation of CLA into erythrocyte membranes were taken from all animals on weekly basis.

Results

Compared to t10, c12-CLA isomer, proportion of c9, t11-CLA isomer in the membrane of erythrocytes was higher for the whole time of the study period. After 4 weeks of feeding, it approaches the plateau. The peak value for both isomers was measured at the end of week 5, with a value of 3.24 g c9, t11-CLA/100 g of fatty acids and a 1.09 g t10, c12-CLA/100 g of fatty acids (p < 0.0001). After cessation of supplementation, the proportion of both isomers gradually decreased to be almost completely washed out—in 7 weeks.

Conclusions

During supplementation with equivalent amounts of CLA isomers, their proportion in membranes of porcine erythrocytes increases with time, with higher proportion of c9, t11-CLA. CLA isomers probably differently incorporate into different cell membranes at different species which could explain its various biological functions.     

Effects of three different conjugated linoleic acid preparations on insulin signalling, fat oxidation and mitochondrial function in rats fed a high-fat diet

To investigate the effects of three different conjugated linoleic acid (CLA) preparations containing different ratios of CLA isomers on insulin signalling, fatty acid oxidation and mitochondrial function, Sprague-Dawley rats were fed a high-fat diet either unsupplemented or supplemented with one of three CLA preparations at 1 % of the diet for 8 weeks. The first CLA preparation contained approximately 30 % cis-9, trans-11 (c9, t11)-CLA isomer and 40 % trans-10, cis-12 (t10, c12)-CLA isomer (CLA-mix). The other two preparations were an 80:20 mix (c9, t11-CLA-mix) or a 10:90 mix of two CLA isomers (t10, c12-CLA-mix). Insulin resistance was decreased in all three supplemented groups based on the results of homeostasis model assessment and the revised quantitative insulin-sensitivity check index. The phosphorylation of insulin receptor substrate-1 on serine decreased in the livers of all three supplemented groups, while subsequent Akt phosphorylation increased only in the t10, c12-CLA-mix group. Both the c9, t11-CLA-mix and the t10, c12-CLA-mix increased the expression of hepatic adiponectin receptors R1 and 2, which are thought to enhance insulin sensitivity and fat oxidation. The c9, t11-CLA-mix increased protein and mRNA levels of PPAR alpha, acyl-CoA oxidase and uncoupling protein, which are involved in fatty acid oxidation and energy dissipation. The c9, t11-CLA-mix enhanced mitochondrial function and protection against oxidative stress by increasing the activities of cytochrome c oxidase, manganese-superoxide dismutase, glutathione peroxidase, and glutathione reductase and the level of GSH. In conclusion, all three CLA preparations reduced insulin resistance. Among them, the c9, t11-CLA-mix was the most effective based on the parameters reflecting insulin resistance and fat oxidation, and mitochondrial antioxidative enzyme activity in the liver.     

共轭亚油酸抑制苯并(a)芘诱导小鼠前胃癌的研究

目的：探讨不同的构成的共轭亚油酸（CLA）对苯并（a)芘[B(a)P]诱导的小鼠前胃癌的抑制作用及可能机制。方法：用B(a)P在昆明种小鼠体内建立前胃癌模型,观察不同构成的CLA对小鼠前胃癌形成的抑制作用,同时采用蛋白印迹法分析小鼠前胃组织中的蛋白表达情况。结果：B(a)P组、75％纯度C9,T11-CAL组、98％纯度c9,t11-CAL组、98％纯度t10,c12-CLA组的前胃肿瘤发生率分别为100．0％、75．0％、69．2％、53．8％;蛋白印迹法分析结果表明,CAL抑制ERK－1的表达,促进MKP－1的表达,而对MEK－1的表达无明显影响,结论：不同构成的CAL对B(a)P诱导小鼠前胃癌均具有抑制作用;CAL影响MAPKs级联反应ERKs及此途径负调控子MKP－1蛋白的表达可能是其抑制肿瘤作用的机制之一。     

Control of rat mammary epithelium proliferation by conjugated linoleic acid.

Past research showed that mammary gland morphogenesis in the pubescent rat was retarded by the feeding of conjugated linoleic acid (CLA). A major objective of the present study was to examine the proliferative activity and the expression of cell cycle regulatory proteins in the developing mammary epithelium of rats fed a mixture of CLA isomers (primarily as free fatty acid c9, t11-CLA and t10,c12-CLA) or a highly enriched natural source of c9,t11-CLA (as triacylglycerol in butterfat). In both experiments, the diets, with or without CLA, were started at weaning and continued for four weeks. The two CLA preparations were equally effective in suppressing bromodeoxyuridine labeling and the expression of cyclin D1 and cyclin A (determined by immunohistochemistry) in the terminal end buds and alveolar clusters of the mammary epithelium while it undergoes extensive ductal branching during pubescence. There was a trend of an increase, although not statistically significant, in the proportion of cells expressing the p16 and p27 cdk inhibitors. A separate experiment was designed to evaluate the effect of c9,t11-CLA (as a free fatty acid of > 90% purity) treatment on the rate of proliferation of the mammary epithelium as the animal matured from weanling to adult. The bromodeoxyuridine labeling data indicated that the mammary epithelium appeared to lose its sensitivity to CLA control of proliferation as it completely filled the fat pad and became quiescent. These observations suggest that the responsiveness of mammary epithelial cells to CLA intervention may be dependent on their proliferative status.     

Control of Rat Mammary Epithelium Proliferation by Conjugated Linoleic Acid

Past research showed that mammary gland morphogenesis in the pubescent rat was retarded by the feeding of conjugated linoleic acid (CLA). A major objective of the present study was to examine the proliferative activity and the expression of cell cycle regulatory proteins in the developing mammary epithelium of rats fed a mixture of CLA isomers (primarily as free fatty acid c9,t11-CLA and t10,c12-CLA) or a highly enriched natural source of c9,t11-CLA (as triacylglycerol in butterfat). In both experiments, the diets, with or without CLA, were started at weaning and continued for four weeks. The two CLA preparations were equally effective in suppressing bromodeoxyuridine labeling and the expression of cyclin D1 and cyclin A (determined by immunohistochemistry) in the terminal end buds and alveolar clusters of the mammary epithelium while it undergoes extensive ductal branching during pubescence. There was a trend of an increase, although not statistically significant, in the proportion of cells expressing the p16 and p27 cdk inhibitors. A separate experiment was designed to evaluate the effect of c9,t11-CLA (as a free fatty acid of >90% purity) treatment on the rate of proliferation of the mammary epithelium as the animal matured from weanling to adult. The bromodeoxyuridine labeling data indicated that the mammary epithelium appeared to lose its sensitivity to CLA control of proliferation as it completely filled the fat pad and became quiescent. These observations suggest that the responsiveness of mammary epithelial cells to CLA intervention may be dependent on their proliferative status.     

Trans-10,cis-12, not cis-9,trans-11, conjugated linoleic acid inhibits G1-S progression in HT-29 human colon cancer cells

Commercial preparations of conjugated linoleic acid (CLA) contain both positional and geometric isomers of octadecadienoic acid, with cis-9,trans-11 CLA (c9t11) and trans-10,cis-12 CLA (t10c12) as the principal isomers. We showed previously that CLA reduced the incidence of colon tumors in rats treated with 1,2-dimethylhydrazine. In addition, our previous in vitro studies showed that t10c12 inhibited the growth of HT-29 and Caco-2 human colon cancer cells, whereas c9t11 had no effect on cell growth. In the present study, to examine the effects of the CLA isomers on cell cycle and cell cycle regulatory proteins, we treated HT-29 cells with various concentrations (0-4 micromol/L) of the individual CLA isomers. A DNA flow cytometric analysis revealed that t10c12 induced a G1 arrest, whereas c9t11 had no effect on the cell cycle. Western blot analysis of total cell lysates revealed no alteration in the protein expression of cyclin A, cyclin D, cyclin E, cyclin-dependent kinase (CDK) 2, or CDK4 due to t10c12 treatment. However, t10c12 substantially increased the protein expression and mRNA accumulation of the CDK inhibitor p21(CIP1/WAF1). The t10c12 isomer increased the association of p21(CIP1/WAF1) with CDK2 and proliferating cell nuclear antigen, but decreased the levels of phosphorylated retinoblastoma protein (Rb), with an increase in the levels of hypophosphorylated Rb protein. An in vitro kinase assay using histone H1 as a substrate showed that the activities of CDK2 were significantly decreased by t10c12. These results indicate that t10c12 exerts its growth inhibitory effects in colon cancer cells through the induction of G1 cell cycle arrest. The induction of p21(CIP1/WAF1) may be one of the mechanisms by which t10c12 inhibits cell cycle progression in HT-29 cells.     

Effects of fatty acids on skeletal muscle cell differentiation in vitro

Previous studies have shown stimulatory effects of linoleic acid (LA, C18:2) on differentiation of rat muscle cells in culture (Allen et al. 1985), but there appears to be little investigation of the effects of other fatty acids. The present study therefore compared the effects of different fatty acids on muscle cell differentiation in vitro. L6 myoblasts were cultured (Dulbecco's Modified Eagles Medium + 10 % fetal calf serum) in six-well plates until 80 % confluent (day 0). Cells were then either harvested or the medium switched to differentiation medium (Dulbecco's Modified Eagles Medium+2 % horse serum), supplemented with fatty acid or drug treatments. Cells were harvested on days 0-5 and assayed for creatine kinase (CK), protein and DNA contents, to give a measure of differentiation (CK/DNA). Initial studies indicated a stimulatory effect of the cis9,trans11 (c9,t11) isomer of conjugated linoleic acid (CLA) relative to control. By contrast, the trans10,cis12 (t10,c12) isomer of CLA inhibited differentiation. Further experiments indicated that inhibition of differentiation by the t10,c12 CLA isomer was dose-dependent (up to 200 microm) and may be via increased cell proliferation. LA and c9,t11 CLA stimulated differentiation at low concentrations (up to 50 microm), but inhibited differentiation at high concentrations (200 microm). In contrast, oleic acid stimulated differentiation at all concentrations, whereas the saturated fatty acid, palmitic acid, had no effect. The mechanism appeared not to involve either peroxisome proliferator-activated receptors alpha or gamma. The data suggest that only unsaturated fatty acids have an effect and the presence or absence of a cis-9 double bond may be important.     

trans-11 18:1 Vaccenic Acid (TVA) Has a Direct Anti-Carcinogenic Effect on MCF-7 Human Mammary Adenocarcinoma Cells

Trans vaccenic acid (TVA; trans-11 18:1) is a positional and geometric isomer of oleic acid and it is the predominant trans isomer found in ruminant fats. TVA can be converted into cis-9, trans-11 conjugated linoleic acid (c9, t11-CLA), a CLA isomer that has many beneficial effects, by stearoyl CoA desaturase 1 (SCD1) in the mammary gland. The health benefits associated with CLA are well documented, but it is unclear whether trans fatty acids (TFAs) from ruminant products have healthy effects. Therefore, the effects of TVA on the proliferation of MCF-7 human breast adenocarcinoma cells and MCF-10A human breast epithelial cells were investigated in the present study. Results showed that TVA inhibited the proliferation of MCF-7 cells but not MCF-10A cells by down-regulating the expression of Bcl-2 as well as procaspase-9. In addition, the suppressive effect of TVA was confirmed in SCD1-depleted MCF-7 cells. Our results suggested that TVA exerts a direct anti-carcinogenic effect on MCF-7 cells. These findings provided a better understanding of the research on the anti-carcinogenic effects of TVA and this may facilitate the manufacture of TVA/c9, t11-CLA fortified ruminant products.     

Antiproliferative effects of conjugated linoleic acid on human colon adenocarcinoma cell line Caco-2

Conjugated linoleic acid (CLA) reduces body fat reserves, and reduces atherogenesis and type II diabetes in animal experiments. It has been reported that CLA have isomeric-specificity, such as c9, t11 CLA with anticancer activity. The antiproliferative effects of two isomers of CLA (c9, t11-CLA, t9, t11-CLA) and their mixture on the human colon adenocarcinoma cell line Caco-2 were investigated in this paper. Caco-2 were incubated in serum-free medium. The antiproliferative effects of different concentrations (0, 25, 50, 100, 200 micromol/L) of linoleic acid (LA), c9, t11-CLA, t9, t11-CLA (the purity of LA and CLA was 96%) and a mixture of c9, t11-CLA and t9, t11- CLA (1:1 v/v) on caco-2 in various action time (1d, 2d, 3d, 4d) were tested in the present study. The antiproliferative effects of four substances in the same concentration and with the same action time were compared. All substances tested could inhibit Caco-2 cell proliferation. The higher anti-proliferation activity in the four materials is the mixture of CLA, then is t9,t11-CLA, c9,t11-CLA, and linoleic acid respectively. The activity is closely related to treatment time and concentration. The isomer t9, t11-CLA itself was found to have antiproliferative activity.     

Effects of dietary cis 9, trans 11-18:2, trans 10, cis 12-18:2, or vaccenic acid (trans 11-18:1) during lactation on body composition, tissue fatty acid profiles, and litter growth in mice

Cis 9, trans 11 (c 9, t11)-18:2 and trans 10, cis 12 (t10, c12)-18:2 are the major conjugated linoleic acid (CLA) isomers in dietary supplements which reduce milk fat content in nursing women. The present study evaluated the effects of each CLA isomer or vaccenic acid on body composition and tissue fatty acids during lactation in mice. Dams were fed 30 g rapeseed oil (control)/kg diet or 20 g control plus 10 g 18:0, trans 11-18:1 (t11-18:1), c 9, t11-18:2, or t10, c12-18:2. Dietary t10, c12-18:2 reduced food intake by 18 % and carcass fat weight of the dams by 49 % compared with the other treatments. Milk fat percentage ranked by treatment was 18:0>t11-18:1=c 9, t11-18:2>t10, c12-18:2. The sum of saturated 12:0 to 16:0 in milk fat was lower when c 9, t11-18:2 was fed compared with the control, 18:0, or t11-18:1 treatments. Dietary t10, c12-18:2 caused further reductions in milk fat 12:0 to 16:0. The proportion of CLA isomers was 3-fold greater in milk fat than in the carcasses of the dams. The pups nursing from the dams fed t10, c12-18:2 had the lowest body weights and carcass fat, protein, and ash contents. Nursing from the dams fed c 9, t11-18:2 also resulted in lower carcass fat compared with the 18:0 or t11-18:1 treatments. The ratios of cis 9-16:1:16:0 or cis 9-18:1:18:0, proxies for Delta(9)-desaturase activity, were markedly lower in the carcasses of the dams and pups fed t10, c12-18:2. The ratio of 20:4n-6:18 : 2n-6, a proxy for Delta(6)- and Delta(5)-desaturase and elongase activity, in the liver of the dams and pups fed t10, c12-18:2 also was lower. Dietary t11-18:1 enhanced the content of c 9, t11-18:2 in milk fat and carcasses. As in previous studies, the reduction in food intake by t10, c12-18:2 could not entirely account for the marked decrease in carcass fat content and milk fat concentration. T10, c12-18:2 probably had a negative effect on Delta(9)-desaturase and mammary de novo fatty acid synthesis. Although these effects need to be confirmed in lactating women, the results suggest that the consumption of supplements containing t10, c12-18:2 should be avoided during the nursing period.