Absorption Kinetics of the Main Conjugated Linoleic Acid Isomers in Commercial-Rich Oil after Oral Administration in Rats.

This study aimed to assess the oral absorption and plasma kinetics of two main isomers contained in commercial conjugated linoleic acid (CLA)-rich oil (Tonalin TG-80), rumenic acid (RA), and C18:2 trans-10, cis-12. The isomer plasma disposition after the single oral dose of 3000 mg of Tonalin TG-80/kg, containing 1200 mg/kg of each isomer, was studied in rats. The isomer plasma concentrations were determined by gas chromatography with flame ionization detection. The plasma kinetics showed rapid oral absorption of RA and C18:2 trans-10, cis-12 (t1/2a 0.34 ± 0.09 and 0.53 ± 0.01 h) and slow elimination (t1/2ß 25.68 ± 3.29 and 18.12 ± 1.71 h); the maximal isomer plasma concentrations (Cmax) of 8.48 ± 0.98 and 7.67 ± 0.80 µg mL-1, respectively, were estimated at 2.08 ± 0.14 and 2.26 ± 0.11 h. Our results from a preclinical kinetic study in rats help to design future studies in humans for evaluating the CLA isomer dose-response.

Preparation of Conjugated Linoleic Acid Microemulsions and their Biodistribution.

Conjugated linoleic acid (CLA) has several beneficial biological properties. Specifically, trans10, cis12-CLA, one of the CLA isomers, has strong physiologic activity against cancer and obesity. However, compared with cis9, trans11-CLA, a naturally occurring CLA isomer, trans10, cis12-CLA tends to be easily metabolized. Therefore, to make efficient use of its biological properties, it is necessary to overcome the rapid clearance of trans10, cis12-CLA from the blood. Here, we employed premix membrane emulsification to prepare two oil-in-water CLA microemulsions (CLA-ME), 100 nm CLA-ME and 200 nm CLA-ME, and investigated their pharmacokinetics in a mouse model. We report that 100 nm CLA-ME contributed to the concentration of blood CLA for longer than 200 nm CLA-ME, indicating that small CLA microparticles were more suitable for maintaining blood trans10, cis12-CLA levels in vivo. However, both CLA-ME could be hardly detected in blood and other tissues 24 h after administration, suggesting that additional strategies for prolonging CLA-ME half-life are required.

Oral Absorption and Disposition of alpha-Linolenic, Rumenic and Vaccenic Acids After Administration as a Naturally Enriched Goat Dairy Fat to Rats.

Although there is extensive information describing the positive biological effects of conjugated linoleic acid and its main isomer rumenic acid (RA; C18:2 cis 9, trans 11), and alpha-linolenic acid (ALA) and vaccenic acid (TVA), data about their bioavailability are not available. In this work, we investigated the oral absorption and disposition of these fatty acids in Wistar rats. A naturally enriched goat dairy fat (EDF) was obtained by supplementing ruminant diets with oils or oilseeds rich in polyunsaturated fatty acids (PUFA). The EDF was administered orally (single dose of 3000 mg EDF/kg body weight equivalent to 153 mg TVA/kg body weight, 46 mg RA/kg body weight and 31 mg ALA/kg body weight), and serial blood and liver samples were collected and TVA, RA and ALA concentrations determined by GC/MS. The fatty acids TVA, RA and ALA were rapidly absorbed (t1/2a, 0.36, 0.66 and 0.76 h, respectively, for plasma) and slowly eliminated (t1/2ß, 17.04, 18.40 and 16.52 h, respectively, for plasma). The maximum concentration (C max) was detected in liver > plasma > erythrocyte. Our study shows that when orally administered EDF, its components TVA, RA and ALA were rapidly absorbed and distributed throughout the body by the blood circulation to exert systemic effects.

The use of 2-dimensional gas chromatography to investigate the effect of rumen-protected conjugated linoleic acid, breed, and lactation stage on the fatty acid profile of sheep milk.

In this study, 2-dimensional gas chromatography (GC × GC) was used to obtain a detailed fatty acid (FA) profile of sheep milk and to evaluate the effects of a rumen-protected conjugated linoleic acid (rpCLA) supply, breed, days in milk (DIM), sampling period, and number of lambs suckling on the FA profile. Twenty-four ewes, from 3 autochthonous breeds of the Veneto Alps (Brogna, Foza, and Lamon), were housed in 6 pens (2 pens/breed), according to DIM (38 ± 23 d) and body weight (61 ± 13 kg). The ewes and their offspring of 3 pens (1 pen/breed) were fed ad libitum a total mixed ration (control), and the other animals received the same diet supplemented with 12 g/d per ewe, plus 4 g/d for each lamb older than 30 d, of an rpCLA mixture. The study lasted 63 d. Two composite milk samples for each ewe were prepared during the first and second months of the trial. The pooled milk samples were analyzed in duplicate for FA profile by 2-dimensional gas chromatography, which allowed us to obtain a detailed FA profile of sheep milk, with 170 different FA detected, including many that were present in small concentrations. The milk relative proportions of individual FA, groups of FA, or FA indices were analyzed by PROC MIXED of SAS (SAS Institute Inc., Cary, NC), considering diet, breed, DIM, and sampling period as sources of variation. The random effect of animal was used to test diet, breed, and DIM, whereas the effects of period were tested on the residual. Breed had a small influence on milk FA profile, mainly on branched- and odd-chain FA. Within breed, animal repeatability for the relative proportions of milk FA was notable for almost all monounsaturated FA and for saturated FA with 14 to 19 carbon atoms, except C16:0, and less so for polyunsaturated FA. The inclusion of rpCLA (CLA cis-9,trans-11 and CLA trans-10,cis-12) increased the presence of the same CLA isomers in the milk as well as that of CLA trans-9,trans-11, and decreased the proportions of de novo-synthesized short-chain FA. From a cluster analysis based on the matrix of correlation coefficients among all FA relative proportions, 3 main FA groups were observed: the first included mainly odd- or branched-chain saturated FA, C18:0, C16:0 and CLA trans-10,cis-12; the second included monounsaturated FA or polyunsaturated FA with 16 to 20 carbons, CLA cis-9,trans-11, and CLA trans-9,trans-11; and the third included short- to medium-chain saturated FA, polyunsaturated FA with 2 to 5 double bonds, and 3 CLA isomers not affected by rpCLA addition (CLA trans-11,cis-13, CLA cis-9,cis-11, and CLA cis-10,cis-12).

Influence of maternal diet enrichment with conjugated linoleic acids on lipoxygenase metabolites of polyunsaturated fatty acids in serum of their offspring with 7,12-dimethylbenz[a]anthracene induced mammary tumors.

Conjugated linoleic acids (CLA), which are a group of naturally occurring in food isomers of linoleic acid, seem to be active in each step of cancer development. There are many possible mechanisms of this action, and interactions with polyunsaturated fatty acids (PUFA) in lipoxygenase (LOX) and cyclooxygenase (COX) pathways are among the most likely ones. The aim of this study was to assess the influence of diet supplementation with CLA of pregnant and breastfeeding Sprague-Dawley female rats on selected polyunsaturated fatty acids and their LOX metabolites concentrations in serum of the progeny with chemically induced mammary tumors. We confirmed that higher supply of CLA in the diet of female rats corresponded with the lower susceptibility to chemically induced mammary tumors in their female offspring. It also influenced the polyunsaturated n-3 and n-6 fatty acid concentrations in serum, as well as the concentrations of their LOX metabolites. The significant negative correlation between the concentrations of two CLA isomers in serum and linoleic acid (p=0.0144, p=0.0098), eicosapentaenoic acid (p=0.0158, p=0.0124), and 5-HEPE (p=0.0014, p=0.01690) and between cis-9, trans-11 CLA and 15-HEPE was detected, whereas arachidonic acid concentration positively correlated with CLA concentration in serum (p=0.0150, p=0.0231). Our results indicate that CLA can compete with PUFA and influence serum concentration of PUFA and their LOX metabolites, which could partly explain the anticancerogenic action of CLA.

Bioavailability and allergoprotective capacity of milk-associated conjugated linoleic acid in a murine model of allergic airway inflammation.

BACKGROUND: Cross-sectional epidemiological studies have demonstrated that farm milk from traditional farm settings possesses allergoprotective properties. Up to now, it has not been clarified which milk ingredient is responsible for protection against allergic diseases. As farm milk is rich in conjugated linoleic acids (CLA), it is hypothesized that this n-3 polyunsaturated fatty acid family contributes to the allergoprotective capacity of farm milk. We aim to prove this hypothesis in a murine model of allergic airway inflammation. METHODS: To prove the bioavailability and allergoprotective capacity of milk-associated CLA in a standardized protocol, milk batches that differed significantly in terms of their CLA content were spray dried and incorporated into a basic diet by substituting the regular sunflower fat fraction. Initially, the milk CLA uptake from the diet was monitored via measurement of the CLA content in plasma and erythrocyte membranes obtained from supplemented mice. To determine whether a milk CLA-enriched diet possesses allergoprotective properties, female Balb/c mice were fed the milk CLA-enriched diet ahead of sensitization and a challenge with ovalbumin (OVA) and the parameters of airway inflammation and eisosanoid pattern were measured. RESULTS: In animals, supplementation with a diet rich in milk CLA resulted in elevated CLA levels in plasma and erythrocyte membranes, indicating bioavailability of milk fatty acids. Though membrane-associated phospholipid patterns were affected by supplementation with milk CLA, this application neither reduced the hallmarks of allergic airway inflammation in sensitized and OVA-challenged mice nor modified the eiconsanoid pattern in the bronchoalveolar lavage fluid of these animals. CONCLUSION: Milk-associated CLA was not capable of preventing murine allergic airway inflammation in an animal model of OVA-induced allergic airway inflammation.

Metabolic interactions between vitamin A and conjugated linoleic acid.

Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR-α and RXR heterodimer. We also present preliminary data that may position PPAR-α at the crossroads between the metabolism of lipids and vitamin A.

A commonly used rumen-protected conjugated linoleic acid supplement marginally affects fatty acid distribution of body tissues and gene expression of mammary gland in heifers during early lactation.

BACKGROUND: Conjugated linoleic acids (CLA) in general, and in particular the trans-10,cis-12 (t10,c12-CLA) isomer are potent modulators of milk fat synthesis in dairy cows. Studies in rodents, such as mice, have revealed that t10,c12-CLA is responsible for hepatic lipodystrophy and decreased adipose tissue with subsequent changes in the fatty acid distribution. The present study aimed to investigate the fatty acid distribution of lipids in several body tissues compared to their distribution in milk fat in early lactating cows in response to CLA treatment. Effects in mammary gland are further analyzed at gene expression level. METHODS: Twenty-five Holstein heifers were fed a diet supplemented with (CLA groups) or without (CON groups) a rumen-protected CLA supplement that provided 6 g/d of c9,t11- and t10,c12-CLA. Five groups of randomly assigned cows were analyzed according to experimental design based on feeding and time of slaughter. Cows in the first group received no CLA supplement and were slaughtered one day postpartum (CON0). Milk samples were taken from the remaining cows in CON and CLA groups until slaughter at 42 (period 1) and 105 (period 2) days in milk (DIM). Immediately after slaughter, tissue samples from liver, retroperitoneal fat, mammary gland and M. longissimus (13th rib) were obtained and analyzed for fatty acid distribution. Relevant genes involved in lipid metabolism of the mammary gland were analyzed using a custom-made microarray platform. RESULTS: Both supplemented CLA isomers increased significantly in milk fat. Furthermore, preformed fatty acids increased at the expense of de novo-synthesized fatty acids. Total and single trans-octadecenoic acids (e.g., t10-18:1 and t11-18:1) also significantly increased. Fatty acid distribution of the mammary gland showed similar changes to those in milk fat, due mainly to residual milk but without affecting gene expression. Liver fatty acids were not altered except for trans-octadecenoic acids, which were increased. Adipose tissue and M. longissimus were only marginally affected by CLA supplementation. CONCLUSIONS: Daily supplementation with CLA led to typical alterations usually observed in milk fat depression (reduction of de novo-synthesized fatty acids) but only marginally affected tissue lipids. Gene expression of the mammary gland was not influenced by CLA supplementation.

Bioavailability of nanoemulsified conjugated linoleic acid for an antiobesity effect.

BACKGROUND: The aim of this study was to enhance the bioavailability of conjugated linoleic acid (CLA), which has low water solubility, using nanoemulsion technology and to evaluate the effects of its improved bioavailability as an antiobesity agent. METHODS: The antiobesity effect of nanoemulsified water-soluble conjugated linoleic acid (N-CLA) was evaluated using in vitro and in vivo studies. Differentiated 3T3-L1 adipocytes were treated with CLA and N-CLA to assess their lipolytic effect. Further, to confirm the antiobesity effect of N-CLA, male Sprague-Dawley rats were randomly separated into four groups, ie, a group fed a normal diet, a group fed a high-fat diet (obesity rat model), a CLA-treated group, and an N-CLA-treated group. RESULTS: N-CLA showed a greater lipolytic effect on differentiated 3T3-L1 adipocytes compared with normal CLA. N-CLA enhanced the release of glycerol from triglycerides, which accumulated in differentiated 3T3-L1 adipocytes. Further, N-CLA enhanced leptin secretion to an extent similar to that of orlistat, an antiobesity agent. In an animal obesity model fed a high-fat diet, N-CLA attenuated accumulation of triglycerides, total cholesterol, and low-density lipoprotein cholesterol in serum, and also significantly decreased the volume of triglycerides and cholesterol in liver tissue. CONCLUSION: These results indicate that N-CLA has a greater antiobesity effect than CLA as a result of its improved bioavailability.

Characterization of the acute lactational response to trans-10, cis-12 conjugated linoleic acid.

Trans-10, cis-12 conjugated linoleic acid (CLA) is a potent inhibitor of milk fat synthesis in the dairy cow. The decrease in milk fat yield during abomasal infusion of CLA reaches a nadir after 3 to 5 d. The acute responses to CLA were evaluated using 4 cows in a crossover design. Cows were milked with the aid of oxytocin every 4h from -28 to 80h and every 6h from 86 to 116h relative to the initiation of abomasal CLA infusion. An initial priming dose of 7.5g of CLA was given at time zero followed by infusion of 2.5g every 4h for 72h. Plasma CLA reached a near-steady-state concentration by 4h, and initial plasma enrichments were greatest in the triglyceride and nonesterified fatty acid fractions. Milk CLA concentration peaked at 6h and reached steady state by 22h. At termination of the infusion, decreases in milk CLA concentration and yield and plasma CLA concentration were best fit by a reciprocal-linear function. Milk fat percentage decreased progressively after 2h and was significant by 14h. Milk fatty acid profile was initially unchanged, but between 18 and 36h after initiation of the CLA dose the proportions of fatty acids progressively shifted, resulting in an increase in fatty acids >C16 and a decrease in fatty acids

The combination of resveratrol and conjugated linoleic acid is not useful in preventing obesity

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Scientific research is constantly looking for new molecules to be used as functional ingredients to combat obesity. The aim of the present study was to analyse whether resveratrol and conjugated linoleic acid (CLA) together could reduce body fat more efficiently than their separate administration. Thirty-six male Wistar rats were randomly divided into four groups: controls rats (C), rats treated with resveratrol (RSV), rats treated with CLA (CLA) and rats treated with a combination of resveratrol and CLA (RSV+CLA). All rats were fed on an obesogenic diet. In RSV and RSV+CLA groups, the rats received 30 mg resveratrol/kg body weight/day. In CLA and RSV+CLA groups, an equimolecular mixture of trans-10,cis-12 and cis-9,trans-11 was added to the diet to reach 0.5% of the active isomer trans-10,cis-12. After 6 weeks of treatment, white adipose tissue from different anatomical locations was dissected and weighed. Serum triacylglycerols, total and HDL cholesterols, glucose, insulin, fructosamine and TNF-á were measured. A glucose tolerance test was also performed. Separately, resveratrol and CLA significantly reduced body fat but did not do so when combined: 20% in the RSV group and 18% in CLA group but 7% in the RSV+CLA group. Resveratrol reduced serum triacylglycerols. No differences were found among groups in serum cholesterol. Resveratrol, as well as the combination RSV+CLA, improved glycaemic control. These results demonstrate that the combination RSV+CLA reduces the effectiveness of each compound on body fat-lowering action, but it maintains the positive effect of resveratrol on glycaemic control. Consequently, this combination has no usefulness in obesity prevention (AU)

Comparison of postprandial oleic acid, 9c,11t CLA and 10t,12c CLA oxidation in healthy moderately overweight subjects.

Few studies report the individual effect of 9c,11t- and 10t,12c-CLA on human energy metabolism. We compared the postprandial oxidative metabolism of 9c,11t- and 10t,12c-CLA and oleic acid (9c-18:1) in 22 healthy moderately overweight volunteers. After 24 weeks supplementation with 9c,11t-, 10t,12c-CLA or 9c-18:1 (3 g/day), subjects consumed a single oral bolus of the appropriate [1-(13)C]-labeled fatty acid. 8 h post-dose, cumulative oxidation was similar for 9c-18:1 and 10t,12c (P = 0.66), but significantly higher for 9c,11t (P < 0.01).

The therapeutic efficacy of conjugated linoleic acid - paclitaxel on glioma in the rat.

Considering the effects of conjugated linoleic acid (CLA) on anti-tumor and anti-angiogenic in brain tumor, synergistic anti-tumor activity with taxane as well as potential activity for transporting chemotherapeutic agents across the blood-brain barrier (BBB), the purpose of this study was to synthesize CLA-paclitaxel (CLA-PTX) conjugate which could reach to the brain tissue and target brain tumor. The CLA was covalently linked to PTX. The conjugate was stable in PBS and rat plasma in vitro and had no microtubule assembly activity in solution and slight effect of arresting cell cycle progression at the G(2)-M phase. The in vitro cytotoxicity of conjugate was lower than that of PTX (p < 0.05). The conjugate showed higher cellular uptake efficiency on C6 glioma cells. The entire pharmacokinetic index revealed the significant enhancement of the conjugate pharmacokinetics compared with that in PTX (p < 0.01). The conjugate, unlike PTX, could distribute in brain tissue and retained higher concentrations throughout 360 h. The anti-tumor efficacy in brain tumor-bearing rats after administering conjugate was significantly higher than that after giving Taxol (p < 0.01). In conclusion, this CLA-PTX conjugate showed great potential to become a new prodrug of PTX and the methodology can be applied to other anticancer drugs.

Delivery of bioactive conjugated linoleic acid with self-assembled amylose-CLA complex.

A delivery system for bioactive conjugated linoleic acid (CLA) through a self-assembled amylose-CLA complex was investigated in comparison with a beta-cyclodextrin (BCD)-CLA complex. Successful complexation between CLA and amylose or BCD was confirmed by differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectral analysis. The yield and complexing percentages were 71.9 and 1.4% for the amylose-CLA complex and 42.3 and 7.7% for the BCD-CLA complex, respectively. However, the amylose-CLA complex showed a better antioxidative protection effect on CLA than BCD-CLA complex, supporting a strong complexing interaction between CLA and amylose shown by thermogravimetric analysis. Compared to 15.9% of CLA released from the BCD-CLA complex under simulated small intestine conditions, 95.6% of CLA was released from the amylose-CLA complex. These results indicate that an amylose-lipid complex self-assembled in the natural way of food component interaction can be used to protect and deliver functional lipids or other bioactive components into the targeted small intestine for absorption.

Human breast milk enrichment in conjugated linoleic acid after consumption of a conjugated linoleic acid-rich food product: a pilot study.

Human breast milk is a complex mixture of organic and inorganic compounds. Some compounds, such as conjugated linoleic acid (CLA), come partly from the mother's diet and are produced by the mother's body and secreted into the milk. Although several studies have examined the effect of chronic CLA supplementation on breast milk CLA appearance, little is known about the transfer of food CLA to breast milk over the short term. The objective of this study was to conduct a preliminary analysis of the kinetics of CLA appearance in breast milk over the short term. Seven women expressed breast milk at 4- to 6-hour intervals for 2 days after eating either CLA-enriched (1912 mg CLA) or control (231 mg CLA) cookies. Milk samples were freeze-dried, fatty acid methyl esters were prepared using methanolic-potassium hydroxide (KOH), and CLA isomers were quantified by gas chromatography. Analysis revealed the following: (1) CLA enrichment of total fatty acids in the breast milk for 48 hours post ingestion of the CLA-enriched cookies was 2.9-fold above control; (2) total breast milk CLA content for 48 hours post CLA-enriched cookies ingestion was 46% greater than post CLA-moderate cookies ingestion; (3) after ingestion of the CLA-enriched cookies, breast milk CLA enrichment plateaued between 8 to 28 hours. This preliminary study suggests that breast milk fatty acids are enriched in CLA compared to control within 28 hours after the ingestion of a CLA-rich food product and invites further research on the extent and timing with which breast milk composition reflects dietary CLA content.

Peroxidación lipídica de microsomas obtenidos del hígado y riñón de rata: efecto del isómero CIS- 9, TRANS-11 del ácido linoléico / Lipid peroxidation of microsomes obtained from rat liver and kidney: effect of CIS-9, TRANS-11_ conjugated linoleic acid isomer

La composición de ácidos grasos, la quimioluminescencia y el índice de peroxidabilidad de microsomas obtenidos de hígado y riñón de rata fueron estudiados después de la administración oral del isómero ácido linoleico conjugado-9-cis, 11-trans (c9-t11-ALC). Mediante la incubación de microsomas en un sistema ascorbato-Fe++ (120 minutos en 37°C), se observó que las cuentas totales por minuto/mg de proteína, originadas por la quimioluminiscencia, eran más bajas en microsomas de hígado y riñón pertenecientes al grupo c9-t11-ALC que en los microsomas obtenidos de grupo control. El efecto de c9-t11-ALC sobre la composición de ácidos grasos poli-insaturados de microsomas hepáticos nativos fue evidenciado por una disminución estadísticamente significativa p<0.007 del ácido linoleico C18:2 n6. Cuando los microsomas peroxidados obtenidos de hígado y riñón, de ambos grupos (control y c9-t11-ALC), fueron comparados con sus respectivos nativos, se observó que C18:2 n6, C20: 4 n6 disminuyeron en todas las membranas microsomales usadas en este trabajo, mientras que en los microsomas obtenidos de hígado del grupo c9-t11-ALC y grupo control también disminuyó C22: 6n3. Por consiguiente, el índice del peroxidabilidad – parámetro basado en el índice máximo de oxidación de ácidos grasos – mostró cambios significativos en microsomas de hígado y riñón. Estos cambios fueron menos pronunciados en las membranas microsomales obtenidas de las ratas que recibieron c9-t11-ALC por vía oral. Nuestros resultados confirmarían y ampliarían observaciones anteriores que indicaron que ALC podría actuar como antioxidante, protegiendo las membranas contra efectos dañinos (AU)

The polyunsaturated fatty acid composition, chemiluminescence and peroxidizability index of microsomes obtained from rat liver and kidney were studied after oral administration of cis-9, trans-11-conjugated linoleic acid isomer (c9-t11-CLA). After incubation of microsomes in an ascorbate Fe++ system (120 min at 37°C) it was observed that the total counts per min/mg protein originated from light emission: chemiluminescence was lower in liver and kidney microsomes in the c9-t11-CLA group than in the microsomes obtained from control group. The effect of c9-t11-CLA on the polyunsaturated fatty acid composition of native liver microsomes was evidenced by a statistically significant p<0.007 decrease of linoleic acid C18:2 n6. When peroxidized microsomes obtained from liver and kidney of both groups (control and c9-t11-CLA) were compared with respective natives, it was observed that C18:2 n6, C20:4 n6 decreased in all membranes used in this work, whereas in microsomes obtained from liver c9-t11-CLA and control groups C22:6 n3 also decreased. As a consequence, the peroxidizability index – a parameter based on the maximal rate of oxidation of fatty acids – showed significant changes in liver and kidney microsomes. These changes were less pronounced in membranes derived from rats receiving c9-t11-CLA per os. Our results would confirm and extend previous observations which indicated that CLA could act as an antioxidant, protecting membranes from deleterious effects (AU)

Conjugated linoleic acids differentially alter polyp number and diameter in the Apc(min/+) mouse model of intestinal cancer.

OBJECTIVE: Dietary conjugated linoleic acids (CLA) have had many health benefits claimed for them, including antineoplastic actions. MATERIALS AND METHODS: The effects of the predominant forms of CLA, namely the c9t11 and t10c12 isomers, or a mixture of these on polyp development, were investigated in the Apc(Min/+) mouse. CLAs have also been linked to altered rates of cell renewal and cell proliferation so this was also studied, as was a further means of increasing tissue mass, namely crypt fission. RESULTS: The stomach and small intestine were significantly heavier in the t10c12, and in the mixture-treated groups (P < 0.001). Crypt fission was increased in the middle small intestine by the t10c12 diet while colonic weight was reduced by c9t11 provision and crypts were 20% shorter. The t10c12 and the mixture significantly reduced polyp number in the proximal small intestine but they increased polyp diameter in the middle and distal small intestine, to an extent that the polyp burden was significantly increased at these sites. All CLAs significantly reduced polyp number in the colon, but the mixture significantly increased polyp diameter in the colon. CONCLUSION: Increased polyp diameter associated with t10c12 diet and especially with the mixture is a cause of concern, as this is the commercially available form. The naturally occurring isomer, c9t11 decreased colonic polyp number and did not increase diameter, suggesting that this natural isomer is the most likely to be protective.

Effect of dietary alpine butter rich in conjugated linoleic acid on milk fat composition of lactating sows.

Multiparous sows (n 17) were included in a controlled cross-over-study in order to investigate the influence of a natural source of conjugated linoleic acid (CLA) (alpine butter) on the milk fatty acid composition of lactating sows (as an animal model for lactating women) and on the growth performance of their progeny. The usual fat source of a standard lactation diet was replaced by either CLA-rich alpine butter or margarine (control diet). Compared with the margarine diet, feeding the alpine butter-supplemented diet increased (P 0.05) affected. Growth performance of the progeny was similar for both dietary treatments. In summary, the findings show that adding alpine butter to the diet does not provoke a milk fat depression and does not alter the composition of total SFA, MUFA and PUFA in sow milk but increases its CLA concentration.

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.

Contribution of rumen protozoa to duodenal flow of nitrogen, conjugated linoleic acid and vaccenic acid in steers fed silages differing in their water-soluble carbohydrate content.

The present experiment was designed to estimate the quantitative contribution of rumen protozoa to the total N, conjugated linoleic acid (CLA) and vaccenic acid (VA; trans-11-18 : 1) flow to the duodenum of steers fed two silage diets: control silage (CS) and silage high in water-soluble carbohydrates (HS). Protozoal duodenal flows were estimated using a real-time PCR assay to quantify the genes encoding protozoal 18S ribosomal RNA. Denaturing gradient gel electrophoresis was used to confirm that the rumen protozoa populations were similar to the protozoal population flowing to the duodenum. Estimated duodenal flow of protozoal N was 14.2 and 18.2 g/d (P>0.05) for animals fed the CS and HS diets respectively. Protozoal flow thus represented between 12 and 15 % of the total N duodenal flow. In terms of fatty acid flow, protozoa accounted for between 30 and 43 % of the CLA and 40 % of the VA reaching the duodenum. The contribution of protozoa to 16 : 0 and 18 : 0 flows to the duodenum was less than 20 and 10 %, respectively. These results show that the fatty acids within protozoa make up a significant proportion of the CLA and VA reaching the duodenum of ruminants.