Immunoglobulin and cytokine production from spleen lymphocytes is modulated in C57BL/6J mice by dietary cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid

We evaluated the effect of cis-9, trans-11 (9c,11t) and trans-10, cis-12 (10t,12c) conjugated linoleic acid (CLA) on the immune system in C57BL/6J mice. Mice were fed experimental diets containing 0% CLA (controls), 1% 9c,11t-CLA, 1% 10t,12c-CLA or a 1:1 mixture (0.5% + 0.5%) of these two CLA isomers for 3 wk. Relative spleen weights of all CLA fed mice were greater than the controls. Spleen lymphocytes isolated from the mice fed 10t,12c-CLA produced more immunoglobulin (Ig)A and IgM but not IgG when stimulated with concanavalin A (ConA) compared with controls. IgA production from unstimulated spleen lymphocytes was greater in the 10t, 12c-CLA group than in controls. Conversely, 9c,11t-CLA did not affect the production of any of the Ig subclasses. Lymphocytes isolated from 9c,11t-CLA fed mice produced more tumor necrosis factor-alpha than the control group. The proportion of B cells in the spleen lymphocyte population was significantly lower in the 9c,11t-CLA group, and higher in the 10t,12c-CLA group than in the controls. Compared with the control group, the percentage of CD4(+) T cells was lower in the 10t,12c-CLA group, and the percentage of CD8(+) T cells was higher in the 9c,11t-CLA group. Furthermore, the percentage of CD8(+) T cells was higher in the 1:1 mixture group than in controls. The CD4(+)/CD8(+) ratio was lower in the 1:1 mixture group than in controls. These results suggest that 9c,11t and 10t,12c-CLA can stimulate different immunological effects and that the simultaneous intake of the two isomers can change the T cell population.     

The change in conjugated linoleic acid concentration in blood of Japanese fed a conjugated linoleic acid diet

Conjugated linoleic acid (CLA) is a collective term used for fatty acids with a conjugated double bond that are geometrical and positional isomers of linoleic acid. Anti-obesity and anti-cancer properties, an immunopotentiation effect, and promotion of bone formation by CLA have been shown in cell culture and animal studies. A mixture of 9c11t- and 10t12c-CLA is now used as a health food supplement after testing in clinical trials. These trials focused on improvement of lipid metabolism by CLA, whereas few studies have examined absorption and metabolism of CLA in humans. In addition, there is no report concerning absorption and metabolism of CLA in Japanese. This study was designed to examine CLA concentration in blood, the elimination rate of CLA, and metabolic differences between 9c11t-CLA and 10t12c-CLA in blood in Japanese who ingested CLA (about 2 g/d, equal weights of 9c11t-CLA and 10t12c-CLA) for 3 wk. Blood samples were collected 1 wk before the 3-wk period, on the first and last days of the period, and 1 wk after the end of the period, and the CLA concentration and distribution in blood were investigated. The CLA concentration in blood was significantly increased by CLA ingestion and reached 36 μmol/L. The CLA concentration in blood one week after the intake period was significantly lower than that at the end of CLA intake. The 10t12c-CLA level in plasma decreased faster than that of 9c11t-CLA. This suggests faster metabolism (fatty acid β oxidation) of 10t12c-CLA compared with 9c11t-CLA.     

两种共轭亚油酸对肥胖大鼠血清脂蛋白组成影响的比较研究

目的比较研究两种主要共轭亚油酸(conjugated linoleic acid,CLA)异构体对肥胖大鼠血脂不同粒径脂蛋白水平的影响。方法以OLETF(Otsuka Long-Evans Tokushima fatty rats)肥胖大鼠为实验动物,对照组喂食AIN76合成饲料,CLA组在饲料中分别添加1%(以质量计)的9c,11t-CLA(9ct组)和1%(以质量计)的10t,12c-CLA(10tc组),喂食2w。以试剂盒方法测定血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)和高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-c)浓度。采用HPLC方法按脂蛋白粒径大小,对血清脂蛋白进行细化分析,测定不同粒径中TC和TG浓度。结果 10t,12c-CLA使血清各脂蛋白中TG浓度均显著下降,总TG浓度降低了22.5%,血清小粒径LDL和大粒径HDL中TC浓度显著增加,总TC浓度增加了26.1%。而9c,11t-CLA使血清总TG增加了22.6%,对总TC浓度无显著影响。结论 10t,12c-CLA具有降低血清TG,升高血清HDL-c的效果,但其对动脉粥样硬化的影响仍有待深入研究。     

Dietary effect of pomegranate seed oil rich in 9cis, 11trans, 13cis conjugated linolenic acid on lipid metabolism in obese,hyperlipidemic OLETF Rats

Conjugated fatty acid, the general term of positional and geometric isomers of polyunsaturated fatty acids with conjugated double bonds, has attracted considerable attention because of its potentially beneficial biological effects. In the present study, dietary effect of pomegranate seed oil rich in punicic acid (9 cis, 11 trans, 13 cis -conjugated linolenic acid; 9c, 11t, 13c-CLNA) on lipid metabolism was investigated in obese, hyperlipidemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After 2 weeks feeding period, OLETF rats revealed obesity and hyperlipidemia compared with their progenitor LETO rats. Feeding of the diet supplemented with 9% safflower oil and 1% pomegranate seed oil (9c, 11t, 13c-CLNA diet) did not affect abdominal white adipose tissue weights and serum lipid levels compared with the diet supplemented with 10% safflower oil (control diet) in OLETF rats. However, the accumulated hepatic triacylglycerol was markedly decreased by 9c, 11t, 13c-CLNA diet in OLETF rats. Activities of hepatic enzymes related to fatty acid synthesis and fatty acid β-oxidation were not altered by 9c, 11t, 13c-CLNA diet. Levels of monounsaturated fatty acid (MUFA), major storage form of fatty acid, in serum triacylglycerol were markedly higher in obese, hyperlipidemic OLETF rats than in lean LETO rats. In addition, 9c, 11t, 13c-CLNA diet significantly decreased MUFA levels in OLETF rats. This is the first study showing that 9c, 11t, 13c-CLNA suppresses delta-9 desaturation in vivo, and we suggest that the alleviation of hepatic triacylglycerol accumulation by 9c, 11t, 13c-CLNA diet was, at least in part, attributable to the suppression of delta-9 desaturation in OLETF rats.     

9trans,11trans conjugated linoleic acid inhibits the development of azoxymethane-induced colonic aberrant crypt foci in rats

We investigated the effects of 9trans,11trans (9t,11t)-conjugated linoleic acid (CLA) isomer on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Male F344 rats were given 2 weekly subcutaneous injections of AOM (20 mg/kg bw) to induce colonic ACF. They also were fed a diet containing either 0.01%, 0.1%, or 1% 9t,11t-CLA for 4 wk starting 1 wk before the first dosing of AOM. The group that received a diet supplemented with 9t,11t-CLA had a significantly lower number of ACF/colon in comparison to the AOM alone group in a dose-dependent manner up to 0.1%. Furthermore, treatment with 9t,11t-CLA induced apoptosis and suppressed cell proliferation activity in the non-lesional crypts. The downregulation of cyclooxygenase-2 and cyclin D1 and the activation of peroxisome proliferators activated receptor gamma were observed in the colonic mucosa of rats fed a diet supplemented with 9t,11t-CLA. Our findings thus provide some novel insight into the chemopreventive effect of 9t,11t-CLA against preinitiation as well as postinitiation stages of colorectal carcinogenesis.     

9trans,11trans Conjugated Linoleic Acid Inhibits the Development of Azoxymethane-Induced Colonic Aberrant Crypt Foci in Rats

We investigated the effects of 9trans,11trans (9t,11t)-conjugated linoleic acid (CLA) isomer on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Male F344 rats were given 2 weekly subcutaneous injections of AOM (20 mg/kg bw) to induce colonic ACF. They also were fed a diet containing either 0.01%, 0.1%, or 1% 9t,11t-CLA for 4 wk starting 1 wk before the first dosing of AOM. The group that received a diet supplemented with 9t,11t-CLA had a significantly lower number of ACF/colon in comparison to the AOM alone group in a dose-dependent manner up to 0.1%. Furthermore, treatment with 9t,11t-CLA induced apoptosis and suppressed cell proliferation activity in the non-lesional crypts. The downregulation of cyclooxygenase-2 and cyclin D1 and the activation of peroxisome proliferators activated receptor γ were observed in the colonic mucosa of rats fed a diet supplemented with 9t,11t-CLA. Our findings thus provide some novel insight into the chemopreventive effect of 9t,11t-CLA against preinitiation as well as postinitiation stages of colorectal carcinogenesis.     

A CLA mixture prevents body triglyceride accumulation without affecting energy expenditure in Syrian hamsters

We examined the effects of feeding conjugated linoleic acids (CLA) to adult male hamsters on several components of energy metabolism and body composition. Hamsters (n = 54) were assigned for 6-8 wk to one of three diets: 1) a standard diet (in percentage energy: lipids, 33, carbohydrates, 49, and proteins, 18); 2) to the standard diet augmented with the 9c,11t-isomer of CLA to 1.6% of energy (R group); or 3) the standard diet augmented with the 9c,11t-isomer and the 10t,12c-CLA isomer to 3.2 (1.6 + 1.6) % of energy (CLA mix group). (15)N uniformly labeled milk-protein was included in the diet to measure the incorporation of dietary protein into liver and muscle. Basal metabolic rate, thermogenic response to feeding and energy expenditure during spontaneous activity or during an exercise at approximately 60% of VO(2max) were measured. Carnitine palmitoyltransferase-I (CPT-I), leptin, insulin and triiodothyronine concentrations, as well as the in vivo overall adiposity changes were also determined. After 6 wk, the whole-body triglyceride content determined in vivo by NMR was significantly higher in the R group than in the control and CLA mix groups. The CLA mix group differed from the others in the lack of body triglyceride accumulation between d 21 and d 45 of the study, and the appearance of a slight insulin-resistance (homeostatic model assessment index, P < 0.05). Paradoxically, the lack of effect on whole-body lipid oxidation was associated with a greater CPT-I-specific activity in tissues of both CLA-fed groups (P < 0.05). No other major effects of CLA feeding were detected. In conclusion, CLA supplementation in hamsters did not affect adipose weight or the components of energy expenditure despite a theoretically higher capacity of red muscle to oxidize lipids. Only a CLA mixture prevented whole-body triglyceride accumulation over time.     

An isomeric mixture of conjugated linoleic acids but not pure cis-9, trans-11-octadecadienoic acid affects body weight gain and plasma lipids in hamsters

We report the effect of an atherogenic diet supplemented with cis-9, trans-11-octadecadienoic acid (c9t11), linoleic acid (LA) or an isomeric mixture of conjugated linoleic acids (CLA) on plasma lipids, weight gain and food intake of male Golden Syrian hamsters. Animals were assigned to three diet groups (n = 10), and fed nonpurified diet, supplemented with 10% hydrogenated coconut oil and 0.05% cholesterol for 6 wk. The first diet group was further supplemented with 1% CLA (CLA group), the second diet group with 0.2% c9t11 (c9t11 group) and the third group with 0.2% LA (LA group). The diets were designed to have equivalent levels of c9t11 in the CLA and c9t11 groups. At 2 and 6 wk of feeding, the CLA group had significantly lower plasma triglyceride and total cholesterol concentrations than either the c9t11 or the LA groups. HDL-cholesterol did not differ among diet groups. The CLA group had significantly lower weight gain but greater food intake than either the c9t11 or the LA groups. There were no significant differences between the c9t11 and the LA groups in any of the variables measured. We conclude that under our experimental conditions of short-term feeding, c9t11, thought to be the active compound in CLA, does not produce the same effect as the isomer mixture.     

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.     

Conjugated linoleic acid attenuates the production and gene expression of proinflammatory cytokines in weaned pigs challenged with lipopolysaccharide

We investigated the anti-inflammatory role of conjugated linoleic acid (CLA) in inflammation-challenged weaned pigs and in in vitro cultured peripheral blood mononuclear cells (PBMCs). To test the hypothesis that inflammation responses can be attenuated by dietary CLA supplementation, we used an acute inflammation model in which pigs were injected with lipopolysaccharide (LPS). After 14 d of dietary supplementation with either 2% soybean oil or 2% CLA, half of the pigs in each diet group were challenged with LPS. Dietary CLA alleviated growth depression and prevented the elevations in production and mRNA expression of proinflammatory cytokines [i.e., interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha] induced by the LPS challenge. CLA enhanced the expression of interleukin-10 (IL-10) and peroxisome proliferator-activated receptor-gamma (PPARgamma) in spleen and thymus. To further elucidate the inhibitory effects and the mechanism of action of CLA on cytokine profiles (i.e., IL-1beta, IL-6, and TNF-alpha), PBMCs were isolated from weaned pigs and cultured in media containing cis-9, trans-11 (9c,11t) CLA and trans-10, cis-12 (10t,12c) CLA. Each CLA isomer suppressed the production and expression of IL-1beta, IL-6, and TNF-alpha, and enhanced PPARgamma activation and gene expression in cultured PBMCs. At the molecular level, the inhibitory actions of CLA on IL-1beta, IL-6, and TNF-alpha are attributable mainly to 10t,12c-CLA and the anti-inflammatory properties of CLA are mediated, at least in part, through a PPARgamma-dependent mechanism.     

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.     

An oil mixture with trans-10, cis-12 conjugated linoleic acid increases markers of inflammation and in vivo lipid peroxidation compared with cis-9, trans-11 conjugated linoleic acid in postmenopausal women

A mixture of trans-10, cis-12 (t10,c12) and cis-9, trans-11 (c9,t11) conjugated linoleic acid (CLA mixture) reduced atherosclerosis in animals, thus the effect of these isomers on endothelial dysfunctions leading to inflammation and atherosclerosis is of interest. We gave 75 healthy postmenopausal women a daily supplement of 5.5 g of oil rich in either CLA mixture, an oil rich in the naturally occurring c9,t11 CLA (CLA milk), respectively, or olive oil for 16 wk in a double-blind, randomized, parallel intervention study. We sampled blood and urine before and after the intervention. The ratios of total cholesterol:HDL cholesterol and concentrations of C-reactive protein, fibrinogen, and plasminogen activator inhibitor-1 were significantly higher in women supplemented with the CLA mixture than in those supplemented with CLA milk. Plasma triacylglycerol was significantly higher and HDL cholesterol was lower in women supplemented with the CLA mixture than with olive oil. Both CLA supplements increased lipid peroxidation, a marker of in vivo oxidative stress measured as urinary free 8-iso-prostaglandin F(2alpha). However, the CLA mixture increased lipid peroxidation more than the CLA milk did. The plasma cytokines interleukin-6 and tumor necrosis factor-alpha were not affected by the treatments, nor were any of the other variables measured. In conclusion, oil containing trans-10,cis-12 CLA has several adverse effects on classical and novel markers of coronary vascular disease, whereas the c9,t11 CLA isomer is more neutral, except for a small but significant increase in lipid peroxidation compared with olive oil.     

Effects of conjugated linoleic acid (CLA) isomers on lipid levels and peroxisome proliferation in the hamster

Effects of the conjugated linoleic acid (CLA) isomers cis-9, trans-11 (c9,t11 CLA) and trans-10, cis-12 (t10,c12 CLA) on lipid metabolism and markers of peroxisome proliferation were investigated in hamsters fed on purified diets containing 30% energy as fat and 0.1 g cholesterol/kg for 8 weeks. Four groups (n 32 each) received diets without CLA (control), with a mixture of equal amounts of c9,t11 and t10,c12 CLA (CLA mix), with c9,t11 CLA, and with t10,c12 CLA. The total amount of CLA isomers was 1.5% energy of 6.6g/ kg diet. CLA was incorporated into glycerides and exchanged for linoleic acid in the diet. Compared with the control, the CLA mix and t10,c12 CLA decreased fasting values of LDL- (21 and 18% respectively) and HDL-cholesterol (8 and 11%), increased VLDL-triacylglycerol (80 and 61%, and decreased epididymal fat pad weights (9 and 16%), whereas c9,t11 CLA had no significant effects. All CLA preparations increased liver weight, but not liver lipids. However, the increase in liver weight was much less in the c9,t11 CLA group (8%) than in the other two groups (25%) and might have been caused by the small amount of t10,c12 CLA present in the c9,t11 CLA preparation. Liver histology revealed that increased weight was due to hypertrophy. Markers of peroxisome proliferation, such as cyanide-insensitive palmitoyl CoA oxidase (EC 1.3.3.6) and carnitine acetyl transferase (EC 2.3.1.7) activities, were not increased by CLA. Both c9,t11 CLA and t10,c12 CLA were incorporated into phospholipids and triacylglycerols, but t10,c12 CLA only about half as much as c9,t11 CLA. In addition, linoleic acid and linolenic acid concentrations were lower in lipids of the t10,c12 CLA group compared with the c9,t11 CLA group. These data suggest that t10,c12 CLA stimulated the oxidation of all C18 polyunsaturated fatty acids. The results indicate that the t10,c12 CLA isomer, and not the so-called natural CLA isomer (c9,t11), is the active isomer affecting lipid levels in hamsters.     

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.     

Dietary trans-10, cis-12 and cis-9,trans-11 conjugated linoleic acids induce apoptosis in the colonic mucosa of rats treated with 1,2-dimethylhydrazine

We have previously shown that a diet containing a mixture of conjugated linoleic acid (CLA) isomers reduces the incidence of colon tumors in rats treated with 1,2-dimethylhydrazine (DMH). The present study examined which of the two main CLA isomers, trans-10,cis-12 CLA (t10c12) or cis-9,trans-11 CLA (c9t11), decreases colon tumor numbers and the mechanisms for this effect. Six-week-old, male Sprague-Dawley rats were intramuscularly injected with 15 mg/kg of DMH twice per week for 6 weeks and fed a control diet, 1% t10c12, or 1% c9t11 for 30 weeks. The experimental diets were initiated simultaneously with DMH injection. The tumor numbers were decreased and the apoptotic index was significantly increased in the colonic mucosa of the t10c12 and c9t11 groups, when the results were compared with those of the control group. The protein levels of Bcl-2 and cyclooxygenase-2 were significantly decreased, but Bax levels were increased in both of the CLA isomer groups. The thromboxane B(2) levels in colonic mucosa were substantially lower in the two CLA isomer groups than in the control group. However, there was no difference in these parameters between the CLA isomer groups. We have demonstrated that diets containing 1% t10c12 and c9t11 were equally effective in reducing tumor numbers and inducing apoptosis in the colonic mucosa of rats treated with DMH. These results indicate that Bcl-2 family protein levels are associated with CLA-induced apoptosis in the colonic mucosa of DMH-treated rats.     

Effect of conjugated linoleic acid isomers on insulin resistance and mRNA levels of genes regulating energy metabolism in high-fat-fed rats

OBJECTIVE: We investigated the effects of specific conjugated linoleic acid (CLA) isomers on glucose metabolism and insulin resistance and on mRNA levels of genes important in glucose and lipid metabolism. METHODS: Sprague-Dawley rats were fed for 8 wk on a high-fat diet (45% kcal from fat) or one of three CLA-supplemented diets (1% CLA) containing differing isomers of CLA, including a mixture of CLAs (CLA mix), cis-9, trans-11-CLA (C9,T11-CLA), or trans-10, cis-12-CLA (T10,C12-CLA). RESULTS: Compared with the high-fat group, all the CLA groups had enhanced glucose tolerance. Insulin resistance index was significantly lower in the CLA-treated groups. No significant difference could be observed in the level of serum lipids between groups and in the activities of phosphoenolpyruvate carboxylase, glucose-6-phosphatase, and glucokinase. However, C9,T11-CLA and T10,C12-CLA significantly increased acyl coenzyme A oxidase mRNA in skeletal muscle. In addition, C9,T11-CLA increased hepatic acyl coenzyme A oxidase mRNA and skeletal muscle uncoupling protein-2 mRNA. The CLA mix showed intermediate effects on the levels of these genes. CONCLUSIONS: The addition of all types of CLA to Sprague-Dawley rats fed a high-fat diet can decrease insulin resistance. Possible mechanisms are increased fat oxidation and energy expenditure by increasing acyl coenzyme A oxidase and uncoupling protein-2 mRNA in the liver and/or skeletal muscle.     

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.     

Effect of dietary conjugated linoleic acid on body composition and energy balance in broiler chickens

The effect of dietary conjugated linoleic acid (CLA) on body composition and energy metabolism was investigated in broiler chickens. Male broiler chicks were assigned to receive either a control diet (1 % sunflower oil) or a diet containing CLA (1 % of a 1:1 mixture of trans-10, cis-12 and cis-9, trans-11 isomers of octadecadienoic acid). The diets were fed ad libitum for 3 weeks and there were eight replicates per diet, each replicate including four chickens so that each treatment had thirty-two animals. The proportion of body fat was lower in the control group than in the CLA group. No significant differences as to the proportions of body water, ash and protein were observed. Feed and energy intake were significantly lower in CLA-fed birds. The percentage of ingested energy lost in excreta was higher after CLA feeding and heat expenditure as a percentage of ingested energy was lower in the CLA-fed group. The CLA-fed group showed a higher percentage of SFA and lower percentages of MUFA and PUFA in carcass fat. It is concluded that CLA stimulated de novo fatty acid synthesis and lowered desaturase activity.     

Changes in body composition with conjugated linoleic acid

Conjugated linoleic acid has been shown to reduce body fat accumulation in several animal models. We have conducted several studies in AKR/J mice showing that CLA reduces body fat accumulation whether animals are fed a high-fat or low-fat diet, with no effect on food intake. One mechanism by which CLA reduces body fat is by increased energy expenditure, which is observed within one week of CLA feeding and is sustained for at least six weeks. The increased energy expenditure is sufficient to account for the decreased fat accumulation. Increased uncoupling protein gene expression does not appear to be involved in the increased energy expenditure. We have observed increased fat oxidation but no decrease in de novo fat biosynthesis with CLA feeding. We have also observed increased liver weights and plasma insulin levels with higher doses of CLA. In all of the studies we have conducted to date we have used a CLA preparation that contains several isomers, primarily c9,t11 and t10,c12. It was assumed that the active form was c9,t11, as CLA was identified as an anticarcinogenic compound from cooked beef, of which the c9,t11 form accounts for 60% to 80% of the CLA. Most of the studies conducted so far must be repeated using the purified isomers in order to determine which isomers are responsible for each of the identified actions of CLA.     

Conjugated linoleic acid (CLA), body fat, and apoptosis

OBJECTIVE: The objective of the study was to determine if consumption of conjugated linoleic acid (CLA) by mice could induce apoptosis in adipose tissue. Other objectives were to determine the influence of feeding mice CLA for < or =2 weeks on body fat, energy expenditure, and feed intake. RESEARCH METHODS AND PROCEDURES: A mixture of CLA isomers (predominantly c9,t11 and t10,c12) was included in the AIN-93G diet at 0, 1, and 2%, and fed to mice for 12 days (Trial 1), or was included at 2% and fed to mice for 0, 5, and 14 days (Trial 2). Feed intake was measured daily and energy expenditure was determined by direct calorimetry on day 9 in Trial 1. Retroperitoneal fat pads were analyzed for apoptosis by determination of DNA fragmentation. RESULTS: Dietary CLA reduced feed intake by 10% to 12% (p < 0.01), but either did not influence or did not increase energy expenditure as indicated by heat loss. Body weight was not influenced by consumption of CLA in Trial 1 but was increased (p < 0.01) by CLA in Trial 2. Weights of retroperitoneal, epididymal, and brown adipose tissues were lower (p < 0.01) in animals fed CLA, although liver weight was increased (p < 0.10; Trial 1) or not changed (Trial 2). Analysis of retroperitoneal fat pad DNA from both trials indicated that apoptosis was increased (p < 0.01) by CLA consumption. DISCUSSION: These results are interpreted to indicate that CLA consumption causes apoptosis in white adipose tissue. This effect occurs within 5 days of consuming a diet that contains CLA.