Conjugated linoleic acid isomers and cancer

We reviewed the literature regarding the effects of conjugated linoleic acid (CLA) preparations enriched in specific isomers, cis9, trans11-CLA (c9, t11-CLA) or trans10, cis12-CLA (t10, c12-CLA), on tumorigenesis in vivo and growth of tumor cell lines in vitro. We also examined the potential mechanisms by which CLA isomers may alter the incidence of cancer. We found no published reports that examined the effects of purified CLA isomers on human cancer in vivo. Incidence of rat mammary tumors induced by methylnitrosourea was decreased by c9, t11-CLA in all studies and by t10, c12-CLA in just a few that included it. Those 2 isomers decreased the incidence of forestomach tumors induced by benzo (a) pyrene in mice. Both isomers reduced breast and forestomach tumorigenesis. The c9, t11-CLA isomer did not affect the development of spontaneous tumors of the intestine or mammary gland, whereas t10, c12-CLA increased development of genetically induced mammary and intestinal tumors. In vitro, t10, c12-CLA inhibited the growth of mammary, colon, colorectal, gastric, prostate, and hepatoma cell lines. These 2 CLA isomers may regulate tumor growth through different mechanisms, because they have markedly different effects on lipid metabolism and regulation of oncogenes. In addition, c9, t11-CLA inhibited the cyclooxygenase-2 pathway and t10, c12-CLA inhibited the lipooxygenase pathway. The t10, c12-CLA isomer induced the expression of apoptotic genes, whereas c9, t11-CLA did not increase apoptosis in most of the studies that assessed it. Several minor isomers including t9, t11-CLA; c11, t13-CLA; c9, c11-CLA; and t7, c11-CLA were more effective than c9, t11-CLA or t10, c12-CLA in inhibiting cell growth in vitro. Additional studies with purified isomers are needed to establish the health benefit and risk ratios of each isomer in humans.     

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-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.     

Effects of ruminant trans fatty acids on cardiovascular disease and cancer: a comprehensive review of epidemiological, clinical, and mechanistic studies

There are 2 predominant sources of dietary trans fatty acids (TFA) in the food supply, those formed during the industrial partial hydrogenation of vegetable oils (iTFA) and those formed by biohydrogenation in ruminants (rTFA), including vaccenic acid (VA) and the naturally occurring isomer of conjugated linoleic acid, cis-9, trans-11 CLA (c9,t11-CLA). The objective of this review is to evaluate the evidence base from epidemiological and clinical studies to determine whether intake of rTFA isomers, specifically VA and c9,t11-CLA, differentially affects risk of cardiovascular disease (CVD) and cancer compared with iTFA. In addition, animal and cell culture studies are reviewed to explore potential pro- and antiatherogenic mechanisms of VA and c9,t11-CLA. Some epidemiological studies suggest that a positive association with coronary heart disease risk exists between only iTFA isomers and not rTFA isomers. Small clinical studies have been conducted to establish cause-and-effect relationships between these different sources of TFA and biomarkers or risk factors of CVD with inconclusive results. The lack of detection of treatment effects reported in some studies may be due to insufficient statistical power. Many studies have used doses of rTFA that are not realistically attainable via diet; thus, further clinical studies are warranted. Associations between iTFA intake and cancer have been inconsistent, and associations between rTFA intake and cancer have not been well studied. Clinical studies have not been conducted investigating the cause-and-effect relationship between iTFA and rTFA intake and risk for cancers. Further research is needed to determine the health effects of VA and c9,t11-CLA in humans.     

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 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.     

Diet supplementation with the cis-9,trans-11 conjugated linoleic acid isomer affects the size of adipocytes in Wistar rats

Previous reports have demonstrated that conjugated linoleic acid (CLA) acts on body fat accumulation in a variety of animal models. The aim of the present study was to investigate the effect of cis (c)-9,trans (t)-11 and t10,c12 CLA isomers on the number and size of adipocytes from the inguinal and retroperitoneal fats in Wistar male rats. A 5.1% palm oil–based diet was supplemented with CLA isomers as follows: 0.6% of c9,t11, 0.6% of t10,c12, 1.3% of c9,t11 and t10,c12 isomers in mixture, and a control nonsupplemented group for comparative purposes. Fat tissues were prepared on microscope slides for histologic examination using an image-analysis software to count the number of adipocytes and measure cell sizes. The results showed that CLA isomers did not affect (P > .05) either final body and fat depot weights or serum lipids (with the exception of triacylglycerols) and adipocytokines (leptin and adiponectin). Animals fed the c9,t11 CLA isomer diet showed larger adipocytes when compared to other groups. Independently of the CLA dietary treatment, retroperitoneal fat showed larger adipocytes (3319 μm²) and therefore a smaller number of adipocytes per unit of area, compared to inguinal fat (3055 μm²). Taken together, the data suggest that a palm oil–based diet supplemented with the c9,t11 CLA isomer in Wistar rats, in contrast to the t10,c12 isomer and the mixture of both isomers, increases adipocyte dimensions in inguinal and retroperitoneal fat depots, while having a minor effect in serum lipids and adipocytokines.     

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.     

Diets rich in conjugated linoleic acid and vaccenic acid have no effect on blood pressure and isobaric arterial elasticity in healthy young men

The objective of this study was to examine the effect on blood pressure (BP) and isobaric arterial elasticity (AE), as a measure of arterial health, of a commercial mixture of conjugated linoleic acids (CLA) and of milk fat produced through livestock feeding to have a high content of vaccenic acid (VA). Healthy young men (n = 60) with a BMI of 22.5 +/- 2 kg/m2 (mean +/- SD) participated in this double-blind, randomized, 5-wk, parallel intervention study. The participants substituted 115 g of their daily fat intake with fat from 1 of 3 test diets: 1) CLA-diet rich in CLA (4.7 g/d of c9,t11- and t10,c12-CLA isomers in equal amounts); 2) VA-diet rich in VA (3.6 g/d); or 3) C-diet, a control diet with a low content of VA and CLA. All test diets were based on milk fat. BP and AE (measured by an oscillometric method) were measured before and after the intervention period. The effects of the test diets did not differ on any outcome variable: e.g., systolic- and diastolic blood pressure (SBP and DBP), pulse pressure (PP), isobaric arterial compliance (AC), distensibility (AD), or volume (AV). In conclusion, diets rich in milk fat and either CLA or VA have no effect on BP or AE indices in healthy young men compared with a control diet.     

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.     

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.     

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.     

Effect of a low-fat diet on fatty acid composition in red cells, plasma phospholipids, and cholesterol esters: investigation of a biomarker of total fat intake

BACKGROUND: The utility of fatty acids (FAs) as biomarkers of total fat intake is unknown. OBJECTIVE: We compared FA changes in red cells (RCs), plasma phospholipids (PLs), and cholesterol esters (CEs) in response to a low-fat diet (LFD) and a moderate-fat diet (MFD) and assessed whether individual or combination of FAs predict LFD. DESIGN: Postmenopausal women (n = 66) were randomly assigned to receive an LFD (17% of energy from fat) or an MFD (34% of energy from fat) for 6 wk. All foods were provided. FAs in diets and blood were determined by gas-liquid chromatography. FA changes between baseline and end of study were compared across diets by using t tests. FA predictors of an LFD were selected by logistic regression. RESULTS: Many FAs in RCs, PLs, and CEs responded differently to the 2 diets. Changes from baseline with an LFD for palmitic acid (16:0) (3-11% increase), behenic (22:0) and lignoceric (24:0) acids (3-20% decrease, in RCs and PLs only), cis-monounsaturated FA (MUFA) (25-35% increase), linoleic acid (18:2n-6) (11-13% decrease), trans octadecanoic acids (trans 18:1) (7-20% decrease), and n-6 highly unsaturated FA (HUFA) (2-8% increase) were significantly different from changes with an MFD. Individually, 18:2n-6 and trans 18:1 were strong predictors of an LFD [receiver operating characteristic (ROC) curves: 0.92-0.80). A logistic regression model with trans 18:1, 18:2n-6, and vaccenic acid (18:1n-7) predicted an LFD with high specificity and sensitivity (ROC curves: 0.99). CONCLUSIONS: Saturated FA, cisMUFA, n-6 HUFA, and exogenous FAs greatly differed in their response to the LFD and MFD. Parallel responses were observed in RCs, PLs, and CEs. A model with a combination of FAs almost perfectly differentiated the consumption of 34% fat from that of 17% fat.     

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 butter high in ruminant trans and monounsaturated fatty acids on lipoproteins, incorporation of fatty acids into lipid classes, plasma C-reactive protein, oxidative stress, hemostatic variables, and insulin in healthy young men

BACKGROUND: Evidence suggests that ruminant trans fatty acids (FAs), such as vaccenic acid, do not increase the risk of ischemic heart disease (IHD). However, the effects of ruminant trans FAs on risk markers of IHD have been poorly investigated. OBJECTIVE: The objective was to investigate the effect of butter with a naturally high content of vaccenic acid and a concomitantly higher content of monounsaturated FAs on classic and novel risk markers of IHD. DESIGN: In a double-blind, randomized, 5-wk, parallel intervention study, 42 healthy young men were given 115 g fat/d from test butter that was high in vaccenic acid (3.6 g vaccenic acid/d) or a control butter with a low content of vaccenic acid. Blood and urine samples were collected before and after the intervention. RESULTS: The intake of the vaccenic acid-rich diet resulted in 6% and 9% lower total cholesterol and plasma HDL-cholesterol concentrations, respectively, than did the intake of the control diet (P = 0.05 and 0.002, respectively), whereas the ratio of total to HDL cholesterol did not differ significantly between the groups. The FA composition of lipid classes reflected the FAs' proportion of the test butter. No other differences were observed. CONCLUSIONS: Butter high in ruminant trans and monounsaturated FAs resulted in significantly lower total and HDL cholesterol than did the control butter with higher amounts of saturated FAs. It may be that the differences were due to the greater content of monounsaturated FAs and the lesser content of saturated FAs in the butter rich in ruminant trans FAs, rather than to the content of vaccenic acid per se.     

Conjugated linoleic acid (CLA)-enriched milk fat inhibits growth and modulates CLA-responsive biomarkers in MCF-7 and SW480 human cancer cell lines

Milk enriched in conjugated linoleic acid (CLA) was obtained from cows on pasture supplemented with full-fat rapeseeds (FFR; 2.26 g cis 9, trans 11 (c9,t11)-CLA/100 g fatty acid methyl esters) and full-fat soyabeans (1.83 g c9,t11-CLA100 g fatty acid methyl esters). A control milk fat (1.69 g c9,t11-CLA/100 g fatty acid methyl esters) was obtained from cows fed on pasture only. The present study assessed the potency of the CLA-enriched milk fats to modulate biomarkers that had previously been observed to respond to c9,t11-CLA in the MCF-7 and SW480 cell lines. Cell numbers decreased (P<0.05) by up to 61 and 58% following the incubation of MCF-7 and SW480 cells, respectively, for 4 d with milk fats (yielding CLA concentrations between 60.2 and 80.6 microM). The FFR milk fat, containing the highest CLA content, increased (P<0.05) [14C]arachidonic acid (AA) uptake into the monoacylglycerol fraction of MCF-7 and SW480 cells while it decreased (P<0.05) uptake into the phospholipid fraction of the latter. This milk fat also decreased (P<0.05) [14C]AA conversion to prostaglandin (PG) E2 while increasing conversion to PGF2alpha in both cell lines. All milk-fat samples increased (P<0.05) lipid peroxidation as measured by 8-epi-PGF2alpha in both cell lines. In SW480 cells the milk-fat samples decreased (P<0.05) bcl-2 and cytosolic glutathione levels while increasing (P<0.05) membrane-associated annexin V levels. All milk-fat samples decreased (P<0.05) the expression of ras in SW480 cells. These data suggest that milk-fat CLA was effective at modulating synthetic CLA-responsive biomarkers.     

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.     

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.