Conjugated linolenic acid is slowly absorbed in rat intestine, but quickly converted to conjugated linoleic acid

We showed previously that alpha-eleostearic acid (alpha-ESA; 9Z11E13E-18:3) is converted to 9Z11E-conjugated linoleic acid (CLA) in rats through a Delta13-saturation reaction. To investigate this further, we examined the absorption and metabolism of alpha-ESA in rat intestine using a lipid absorption assay in lymph from the thoracic duct. In this study, we used 4 test oils [tung oil, perilla oil, CLA-triacylglycerol (TG), and pomegranate seed oil, containing alpha-ESA, alpha-linolenic acid (LnA; 9Z12Z15Z-18:3), CLA, and punicic acid (PA; 9Z11E13Z-18:3), respectively]. Emulsions containing the test oils were administered to rats, and lymph from the thoracic duct was collected over 24 h. The positional and geometrical isomerism of CLA produced by PA metabolism was determined using GC-electron impact (EI)-MS and (13)C-NMR, respectively; the product was confirmed to be 9Z11E-CLA. A part of alpha-ESA and PA was converted to 9Z11E-CLA 1 h after administration; therefore the lymphatic recoveries of alpha-ESA and PA were modified by the amount of recovered CLA. Cumulative recovery of CLA, alpha-ESA, and PA was lower than that of LnA only during h 1 (P < 0.05), and cumulative recovery of alpha-ESA and PA was significantly lower than that of LnA and CLA for 8 h (P < 0.05). Therefore, the absorption rate was LnA > CLA > alpha-ESA = PA. The conversion ratio of alpha-ESA to 9Z11E-CLA was higher than that of PA to 9Z11E-CLA over 24 h (P < 0.05). These results indicated that alpha-ESA and PA are slowly absorbed in rat intestine, and a portion of these fatty acids is quickly converted to 9Z11E-CLA.     

The metabolic conversion of 9,11,13-eleostearic acid (18:3) to 9,11-conjugated linoleic acid (18:2) in the rat

The presence of a significant amount of 9,11-conjugated linoleic acid (CLA, 9,11-18:2) was confirmed in the liver and plasma lipids of rats fed a 1% (w/w % of diet) eleostearic acid (ESA, 9,11,13-18:3) diet for 4 wk. The chemical structure of the 9,11-CLA apparent in the tissue lipids was identified by gas chromatography-electron impact mass spectrometry after its conversion to a 4,4-dimethyloxazoline derivative. The concentration of CLA in the total fatty acids of the liver and plasma lipids reached to about 1%, for each in the CLA-supplemented rats, while reaching 3.2% and 2.5%, respectively, in the ESA-supplemented rats. The results suggest that alpha-ESA is metabolized partially to CLA via a delta 13-saturation reaction in the rat. Some biological activities observed in alpha-ESA-fed animals may be ascribed also to CLA that is formed from ESA in the body.     

cis-9, trans-11 conjugated linoleic acid is synthesized directly from vaccenic acid in lactating dairy cattle

The utilization of (13)C-labeled vaccenic acid (VA) by lactating dairy cows to synthesize cis-9, trans-11 conjugated linoleic acid (CLA) was investigated. Primiparous ruminally cannulated Holstein cows (n = 3) were abomasally infused with 1.5 g of VA-1-(13)C. Blood and milk samples were taken frequently before and after VA infusion. Milk and plasma lipid were extracted using chloroform:methanol. Plasma lipid was separated into triacylglycerol (TG), cholesterol ester (CE), phospholipid (PL), nonesterified fatty acid (NEFA), and mono- and diacylglycerol (MDG) fractions. Lipid was methylated, converted to dimethyl disulfide and Diels-Alder adducts, and analyzed by GC-MS. Increased enrichment of (13)C was determined using a 2-sample t test for each sample time compared with -24 h, with significance declared at P < 0.05. Enrichment in milk fat VA was detected at 4 (3.0%), 8 (8.3%), 12 (4.1%), 16 (2.2%), and 20 h (0.8%). Enrichment in VA was also detected in plasma TG, NEFA, PL, and MDG. Enrichment in milk fat cis-9, trans-11 CLA, the Delta9-desaturase product of VA, was detected at 4 (2.6%), 8 (6.6%), 12 (3.4%), 16 (1.7%), and 24 h (0.7%). Enrichment was not detected in cis-9, trans-11 CLA for any plasma lipid fraction. Modeling of the data showed the exponential decay in (13)C enrichment over time for both VA and cis-9, trans-11 CLA in milk fat. Conversion of dietary VA to cis-9, trans-11 CLA endogenously was confirmed with the mammary gland being the primary site of Delta9-desaturase activity; approximately 80% of milk fat cis-9, trans-11 CLA originated from VA.     

Cis-9, trans-11 conjugated linoleic acid is synthesized from vaccenic acid in lactating women

We studied the incorporation of the trans-11 vaccenic-1-(13)C acid ((13)C-VA) into milk and endogenous synthesis of cis-9, trans-11 conjugated linoleic acid (CLA) in lactating women. Subjects (n = 4) were 247 +/- 30 d postpartum, weighed 70.8 +/- 3.7 kg, breast-fed at least 6 times/d and consumed self-selected diets. After an overnight fast, they consumed the (13)C-VA (2.5 mg/kg body wt). Milk samples were obtained by complete breast expression at 0, 2, 4, 8, 12, 18, 24, and 48 h post-(13)C-VA ingestion. Lipid was extracted using chloroform:methanol. Fatty acids were methylated and converted to dimethyl disulfide and Diels-Alder derivatives before analysis by gas chromatography mass spectrometry. The mean (13)C-enrichment of milk VA was 3.1% at 8 h and reached maximal enrichment of 7.6% at 18 h. The (13)C enrichment of milk cis-9, trans-11 CLA reached a maximum of 0.4% at 18 h, confirming its conversion of VA to the Delta9-desaturase enzyme product. In the subjects examined, a portion (<10%) of the cis-9, trans-11 CLA present in milk was endogenously synthesized from VA.     

Intestinal bifidobacteria that produce trans-9, trans-11 conjugated linoleic acid: a fatty acid with antiproliferative activity against human colon SW480 and HT-29 cancer cells

Bifidobacterium breve species of human intestinal origin have the ability to synthesize cis-9, trans-11 (c9, t11) conjugated linoleic acid (CLA) from free linoleic acid. In this study, the ability of Bifidobacterium species to isomerize C(18) polyunsaturated fatty acids was investigated, and the antiproliferative activities of the two main microbially produced CLA isomers were assessed. Linoleic acid was converted principally to c9, t11 CLA and lesser amounts of t9, t11 CLA, whereas c9, t11 CLA was converted mainly to t9, t11 CLA. Likewise, t10, c12 CLA was converted principally to t9, t11 CLA, which was incorporated into the bacterial cell membranes. To examine the antiproliferative effect of the two main CLA isomers formed, SW480 and HT-29 human colon cancer cells were cultured in the presence of c9, t11 CLA and t9, t11 CLA. The t9, t11 CLA had a more potent antiproliferative effect than c9, t11 CLA. It is tempting to suggest that the ability of Bifidobacterium to produce such bioactive metabolites may be associated with the beneficial effects of bifidobacteria present in the human gastrointestinal tract.     

The anticarcinogenic effect of trans-11 18:1 is dependent on its conversion to cis-9, trans-11 CLA by delta9-desaturase in rats

The present study was designed to determine whether the ability of vaccenic acid (trans-11 18:1; VA) to reduce the risk of chemically induced mammary carcinogenesis in rats is direct or is mediated via conversion to cis-9, trans-11 conjugated linoleic acid (CLA). We previously reported that dietary VA caused a dose-dependent increase in the accumulation of CLA in the mammary fat pad, which was accompanied by a parallel decrease in the risk of mammary tumorigenesis. Specifically, our objective was to determine whether inhibiting Delta9-desaturase with cyclopropenoic fatty acids, supplied by sterculic oil (SO), would reverse the cancer-protective effect observed with a dietary supplement of VA-enriched butter. Female Sprague-Dawley rats were injected with a single dose of carcinogen (methylnitrosourea) and were fed 1 of 4 diets: 1) low VA (0.13% of diet), 2) low VA + SO (0.4% of diet), 3) high VA (1.60% of diet), and 4) high VA + SO. After 6 wk, the mammary glands were evaluated histologically for the appearance of premalignant lesions and were stained with bromodeoxyuridine to determine the extent of cell proliferation, and fatty acids were analyzed in plasma, liver, and mammary fat pad. The VA-enriched diet increased the tissue content of CLA, reduced the risk of developing premalignant lesions, and decreased the proliferative activity of premalignant cells in the mammary gland. Treatment with SO reversed the effects of VA. The anticarcinogenic effect of VA is predominantly, perhaps exclusively, mediated through its conversion to cis-9, trans-11 CLA via Delta9-desaturase, and when this conversion is blocked by SO, the biological response to VA is attenuated.     

Incorporation of cis-9, trans-11 conjugated linoleic acid and vaccenic acid (trans-11 18 : 1) into plasma and leucocyte lipids in healthy men consuming dairy products naturally enriched in these fatty acids

The present study investigated whether consuming dairy products naturally enriched in cis-9, trans-11 (c9,t11) conjugated linoleic acid (CLA) by modification of cattle feed increases the concentration of this isomer in plasma and cellular lipids in healthy men. The study had a double-blind cross-over design. Subjects aged 34-60 years consumed dairy products available from food retailers for 1 week and then either control (0.17 g c9,t11 CLA/d; 0.31 g trans-vaccenic acid (tVA)/d) or CLA-enriched (1.43 g c9,t11 CLA/d; 4.71 g tVA/d) dairy products for 6 weeks. After 7 weeks washout, this was repeated with the alternate products. c9,t11 CLA concentration in plasma lipids was lower after consuming the control products, which may reflect the two-fold greater c9,t11 CLA content of the commercial products. Consuming the CLA-enriched dairy products increased the c9,t11 CLA concentration in plasma phosphatidylcholine (PC) (38 %; P = 0.035), triacylglycerol (TAG) (22 %; P < 0.0001) and cholesteryl esters (205 %; P < 0.0001), and in peripheral blood mononuclear cells (PBMC) (238 %; P < 0.0001), while tVA concentration was greater in plasma PC (65 %; P = 0.035), TAG (98 %; P = 0.001) and PBMC (84 %; P = 0.004). Overall, the present study shows that consumption of naturally enriched dairy products in amounts similar to habitual intakes of these foods increased the c9,t11 CLA content of plasma and cellular lipids.     

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.     

Trans-11-18 : 1 is effectively Delta9-desaturated compared with trans-12-18 : 1 in humans

The aim of this human intervention study was to evaluate the Delta9-desaturation of trans-11-18 : 1 (trans-vaccenic acid; tVA) to cis-9,trans-11-18 : 2 (c9,t11 conjugated linoleic acid; CLA) and of trans-12-18 : 1 (t12) to cis-9,trans-12-18 : 2 after a short-term (7 d) and a long-term (42 d) supplementation period. The conversion rates of both trans-18 : 1 isomers were estimated by lipid analysis of serum and red blood cell membranes (RBCM). Subjects started with a 2-week adaptation period without supplements. During the 42 d intervention period, the diet of the test group was supplemented with 3 g/d of tVA and 3 g/d of t12. The diet of the control group was supplemented with a control oil. Serum tVA and t12 levels in the test group increased by fivefold and ninefold after 7 d, respectively, and by eight- and 12-fold after 42 d, respectively, when compared with the adaptation period (P< or =0.002). The serum c9,t11 CLA levels increased by 1.7- and 2.0-fold after 7 d and 42 d, respectively (P< or =0.001). After 42 d, the test group's RBCM c9,t11 CLA content was elevated by 20 % (P=0.021), whereas in the control group it was decreased by 50 % (P=0.002). The conversion rate of tVA was estimated at 24 % by serum and 19 % by RBCM. No increase in c9,t12-18 : 2 was observed in the serum and RBCM, and thus no conversion of t12 could be determined. In conclusion, the endogenous conversion of dietary tVA to c9,t11 CLA contributes approximately one quarter to the human CLA pool and should be considered when determining the CLA supply.     

cis-9, trans-11 CLA derived endogenously from trans-11 18:1 reduces cancer risk in rats

The present study was designed to examine the effects of increasing dietary levels of vaccenic acid (VA) and cis-9, trans-11 conjugated linoleic acid (CLA) on chemically induced mammary carcinogenesis in rats. Both fatty acids were provided as a natural component in butter fat. The conversion of VA to CLA by delta9-desaturase was documented previously in several species, including rats and humans. Specifically, our objective was to determine the relative contribution of dietary VA and CLA to the tissue concentration of CLA and its ability to inhibit the development of mammary carcinomas. A total of 7 diets were formulated with varying levels of CLA and VA. The overall dietary treatment scheme was designed to evaluate the modulation of mammary cancer risk by 1). small increases of CLA in the presence of a low level of VA and 2). more substantial increases of VA against a background of low levels of CLA. As expected, small increases in dietary CLA at the low end of the CLA dose-response range did not reduce tumorigenesis. In contrast, there was a distinct and marked inhibitory response to VA that was dose dependent. The effect of VA was magnified in this experiment because the dose range of VA tested was much broader than that of CLA. Fatty acid analysis showed that the conversion of dietary VA to CLA resulted in a dose-dependent increase in the accumulation of CLA in the mammary fat pad, which was accompanied by a parallel decrease in tumor formation in the mammary gland. The finding confirms that the conversion of VA to CLA is as important for cancer prevention as the dietary supply of CLA. Thus, VA is also anticarcinogenic, and VA and CLA represent functional food components that are present in ruminant fat.     

Transfer of absorbed cis-9, trans-11 conjugated linoleic acid into milk is biologically more efficient than endogenous synthesis from absorbed vaccenic acid in lactating cows

Cis-9, trans-11, the major isomer of conjugated linoleic acid (CLA) in bovine milk fat, is derived from ruminal biohydrogenation of 18:2 (n-6) and endogenous conversion of trans-11 18:1 (vaccenic acid; VA) in the mammary gland. Most evidence to date suggests that endogenous synthesis is the major source of cis-9, trans-11 CLA, but the extent of VA desaturation is less well defined. Four lactating cows were used in consecutive 4 x 4 Latin squares to examine changes in milk fatty acid composition and secretion in response to abomasal infusions of lipid supplements enriched with cis-9, trans-11 CLA (88.8%) or VA (29.4%). Treatments were infused over 4-d, followed by a 3-d washout, during 7 d experimental periods and administered to deliver 0, 3, 6, and 12 g cis-9, trans-11 CLA/d (Expt. 1) or 0, 7.5, 15 and 30 g VA/d (Expt. 2). Infusions of cis-9, trans-11 CLA increased linearly milk cis-9, trans-11 CLA concentrations from 0.68 to 1.46 g/100 g fatty acids. Abomasal infusions of VA increased linearly milk VA and cis-9, trans-11 CLA content from 1.22 to 2.72 and 0.61 to 1.24 g/100 g fatty acids, respectively. Changes in milk fatty acid secretion indicated that 28.9% of VA was converted to cis-9, trans-11 CLA. Results provide evidence that conversion by Delta9-desaturase to cis-9, trans-11 CLA in the lactating cow is independent of postruminal VA supply. In conclusion, endogenous synthesis via VA was equivalent to approximately 21% of the response to increases in cis-9, trans-11 CLA available for absorption.     

Isomer specificity of conjugated linoleic acid (CLA): 9E,11E-CLA

Conjugated linoleic acids (CLA) were identified in 1980''s, since then it has been intensively studied due to its various beneficial health effects such as anti-inflammatory, anti-atherogenic, anti-carcinogenic and anti-diabetic/obesity effects. Isomer specificity of a number of CLA isomers, especially predominant isomer 9Z,11E- and 10E,12Z-CLA, is now recognized. However, the less prevalent CLA isomers have not been well characterized. Recently, studies have reported the distinctively different effects of 9E,11E-CLA in colon cancer cells, endothelial cells, and macrophage cells compared to the rest of CLA isomers. In this review, various effects of CLAs, especially anti-inflammatory and anti-atherogenic effects, will be discussed with focusing on the isomer-specific effects and potential mechanism of action of CLA. At last, recent studies about 9E,11E-CLA in in vitro and animal models will be discussed.     

Metabolic effects of dietary conjugated linoleic acid (CLA) isomers in rats

To know the effect of individual conjugated linoleic acid (CLA) isomers on lipid metabolism, male rats were fed diets containing either linoleic acid (LA, a control fatty acid), CLA containing mainly 9c,11t-isomer, 10t,12c-isomer (at the 0.8% level) or an equivalent mixture of these isomers (at the 0.4% level) for 26 days. Although there were no differences in food intake and body weight gain among the groups, the food efficiency was low in rats fed the CLA containing 10t,12c-isomer in comparison with those fed 9c,11t-CLA. The weight of white (epididymal and perirenal) adipose tissues decreased in all CLA groups, while that of brown adipose tissue increased in rats fed 10t,12c-CLA, the difference between 9c,11t- and 10t,12c-isomers being significant. The concentration of serum total cholesterol, triacylglycerol and phospholipid tended to be lower in rats fed CLA preparations containing 10t,12c-CLA, while there was a trend toward an increasing concentration of serum HDL-cholesterol in all CLA groups. The rate of fatty acid β-oxidation in the liver peroxisomes was slightly higher in rats fed CLA than in those fed LA, and the activity of mitchondrial carnitine parmitoyltranceferase (CPT) in the CLA-mix group significantly increased compared to the LA group. The effect of CLA on the concentration of spleen and serum IgE, IgG and IgA level was variable. No CLA effect was observed on the concentration of serum leptin and TNF-. Thus, individual isomers of CLA may have different effects on some metabolic parameters in rats. The results also suggested a probable interaction of different isomers on lipid metabolism.     

Cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid isomers do not modify body composition in adult sedentary or exercised rats

Dietary CLA isomers were shown to reduce adipose tissues in growing animals, mainly in mice, but their effects in adult animals remain unclear. This study was conducted to determine whether these effects depend on the isomer fed, on physical activity, or on the initial level of body fat. Male Wistar rats (4 mo old) were fed for 6 wk diets containing either no CLA, the cis-9, trans-11 CLA isomer (10 g/kg), the trans-10, cis-12 CLA isomer (10 g/kg), or both isomers (10 g/kg each). Half of the rats were assigned to exercise by treadmill running (1 h/d, 22 m/min). The initial body fat level was normal (12.7%) in a first trial, and high (18.9%) in a second trial. Chemical and anatomical body compositions were determined by chemical analysis and organ dissection. In both trials, the CLA diets, whatever the isomer, had no effect on food intake and body weight changes, on body chemical composition (fat, protein and water contents or gains), or on the body anatomical composition (weights or gains in epididymal and perirenal adipose tissues, in liver and in 4 muscles). There was no interaction between CLA treatment and physical activity. In conclusion, adult male rats do not appear to be responsive to the fat-to-lean partitioning effect of CLA described in growing rats. This was not affected by exercise or initial body fat level.     

Vaccenic acid feeding increases tissue levels of conjugated linoleic acid and suppresses development of premalignant lesions in rat mammary gland

The objective of this report was to determine whether vaccenic acid (t11-18:1) is converted efficiently to conjugated linoleic acid (c9,t11-18:2, CLA) in rats via the delta 9-desaturase reaction and, if so, whether vaccenic acid could substitute for CLA as an anticancer agent. In Study 1, rats were fed 1%, 2%, or 3% vaccenic acid in their diet, and tissue levels of CLA and CLA metabolites were determined in liver and mammary gland. In general, concentrations of CLA and CLA metabolites increased proportionately with an increase in vaccenic acid intake, at least up to the 2% dose level. Beyond this dose, there was clearly a plateauing effect. Thus vaccenic acid concentration increased from an undetectable level in the control to 78.5 nmol/mg lipid in the liver of rats fed a 2% vaccenic acid diet. This was accompanied by an increase in CLA from 2.3 to 33.6 nmol/mg lipid. These changes were also mirrored in the mammary gland, where increases in vaccenic acid (from 27.5 to 163.2 nmol/mg lipid) and CLA (from 17.8 to 108.9 nmol/mg lipid) were similarly observed. Vaccenic acid at 2% produced a CLA concentration in the mammary gland that was historically associated with a positive response in tumor inhibition based on our past experience. This provided the basis for selecting 2% vaccenic acid in Study 2, which was designed to evaluate its efficacy in blocking the development of premalignant lesions in the rat mammary gland. In this experiment, formation of histologically identifiable pathology due to intraductal proliferation of terminal end bud cells of mammary epithelium was used as the end point of analysis at 6 wk after carcinogen administration. Treatment with vaccenic acid reduced the total number of these premalignant lesions by approximately 50%. We hypothesize that the anticancer response to vaccenic acid is likely to be mediated by its endogenous conversion to CLA via delta 9-desaturase.     

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.     

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.     

气相色谱分析法测定酸奶和奶油中c9,t11-共轭亚油酸的含量

目的：建立用程序升温气相色谱法测定奶制品中c9,t11-共轭亚油酸含量的方法。方法：首先建立本实验方法的气相色谱分析条件；采用内标法，将样品提取、甲酯化后，进行气相色谱分析；同时对实验方法的回收率、精密度也进行了分析。结果：能够将甲酯化亚油酸和c9,t11-共轭亚油酸很好地分离；内标物十七烷酸甲酯与其它脂肪酸甲酯能够完全分离，并不受样品中其它组分的影响；c9,t11-共轭亚油酸的含量分别为：帕玛拉特天然酸奶饮品10．78mg/g，万家宝原味酸奶（搅拌型）5．03mg/g，奶油22．54mg/g脂肪。实验方法的回收率为84．74％，RSD＝3．73％；精密度RSD＝2．58％。结论：所建立的实验条件准确可靠，这对于分析奶及奶制品来源的c9,t11-共轭亚油酸含量具有指导意义。     

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.     

Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men

OBJECTIVES: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. DESIGN: Double-blind, randomized, parallel, reference-controlled intervention study. SUBJECTS AND INTERVENTION: Seventy-one healthy males aged 31-69 y received one of the following treatments: (1). mixture of 50% c9,t11 CLA and 50% t10,c12 CLA isomers (CLA 50:50); (2). mixture of 80% c9,t11 CLA and 20% t10,c12 CLA isomers (CLA 80:20); and (3). sunflower oil fatty acids (reference). The treatments were given as supplements in softgel capsules providing a total of 1.7 g (c9,t11+t10,c12) CLA fatty acids (50:50) or 1.6 g (c9,t11+t10,c12) CLA glycerides (80:20) per day in treatment groups for 12 weeks. RESULTS: Almost twice as many subjects reached protective antibody levels to hepatitis B when consuming CLA 50:50 fatty acids (15/24, 62%) compared with subjects consuming the reference substance (7/21, 33%, P=0.075). In subjects consuming CLA 80:20 glycerides this was 8/22 (36%). Other aspects of immune function, ie DTH responses, NK cell activity, lymphocyte proliferation and production of TNF-alpha, IL1-beta, IL6, IFN-gamma, IL2, IL4, and PGE(2), were not affected. CONCLUSION: This is the first study that suggests that CLA may beneficially affect the initiation of a specific response to a hepatitis B vaccination. This was seen in the CLA 50:50, but not in the CLA 80:20 group.