Dietary calcium impairs tomato lycopene bioavailability in healthy humans.

Lycopene (LYC) bioavailability is relatively low and highly variable, because of the influence of several factors. Recent in vitro data have suggested that dietary Ca can impair LYC micellarisation, but there is no evidence whether this can lead to decreased LYC absorption efficiency in humans. Our objective was to assess whether a nutritional dose of Ca impairs dietary LYC bioavailability and to study the mechanism(s) involved. First, in a randomised, two-way cross-over study, ten healthy adults consumed either a test meal that provided 19-mg (all-E)-LYC from tomato paste or the same meal plus 500-mg calcium carbonate as a supplement. Plasma LYC concentration was measured at regular time intervals over 7 h postprandially. In a second approach, an in vitro digestion model was used to assess the effect of increasing Ca doses on LYC micellarisation and on the size and zeta potential of the mixed micelles produced during digestion of a complex food matrix. LYC bioavailability was diminished by 83 % following the addition of Ca in the test meal. In vitro, Ca affected neither LYC micellarisation nor mixed micelle size but it decreased the absolute value of their charge by 39 %. In conclusion, a nutritional dose of Ca can impair dietary LYC bioavailability in healthy humans. This inhibition could be due to the fact that Ca diminishes the electrical charge of micelles. These results call for a thorough assessment of the effects of Ca, or other divalent minerals, on the bioavailability of other carotenoids and lipophilic micronutrients.

Rapid reduction of liver steatosis in omega3-depleted rats injected with a novel lipid emulsion.

The bolus intravenous administration of a novel medium-chain triglyceride: fish oil emulsion (MCT:FO) to normal subjects was recently found to increase within 60 min the amount of long-chain polyunsaturated omega3 fatty acids ( omega3) in platelet and leukocyte phospholipids and, hence, was proposed as a tool to prevent such pathological events as cardiac arrhythmia in selected patients who have to undergo urgent anesthesia and/or surgery. This study investigates whether other cells located outside the vascular bed may also benefit from this procedure for replenishing phospholipids with omega3. For such a purpose, the MCT:FO emulsion (1.0 ml) was injected into normal or omega3-depleted rats examined, one hour later, for the content and fatty acid pattern of liver triglycerides and phospholipids. Control experiments included the administration of saline or a medium-chain triglyceride:olive oil emulsion. The results reveal that the bolus intravenous injection of MCT:FO to the omega3-depleted rats resulted in the enrichment of liver phospholipids in omega3 and a marked reduction in hepatic steatosis. In conclusion, it is proposed that such a procedure may indeed allow a rapid supply of omega3 not only to circulating and vascular endothelial cells but also to extravascular cells, with a resulting correction of the biochemical and biophysical defects linked to a deficiency in these fatty acids.

Dietary cyclic fatty acids derived from linolenic acid do not exhibit intrinsic toxicity in the rat during gestation.

Heating oils and fats may lead to cyclization of polyunsaturated fatty acids, especially those showing multiple double bonds like linolenic acid. Cyclohexenyl and cyclopentenyl fatty acids are subsequently present in some edible oils and these were suspected to induce metabolic disorders. When fed during gestation in the rat, cyclic fatty acids were historically reported to induce high mortality of the neonates. Nevertheless, none of these studies have been performed with cyclic fatty acids fed as triacylglycerols, limiting the nutritional value of the conclusions. Therefore, we assessed the toxicity of a diet containing 0.7% of cyclic fatty acids fed as triacylglycerols during gestation and the first days of life in the rat. In this work, we report no deleterious effect of cyclic fatty acids in the mothers and neonates. However, cyclic fatty acids induced a tremendous insulinopenia in the mothers and pups that was associated with the reduction of food intake in the gestating females. Such a finding may be a plausible explanation for the adverse effects of cyclic fatty acids observed previously with higher doses of cyclic fatty acids. Based on present data, on previous ones showing elimination of cyclic fatty acids, and considering their low amounts in the diet, we suggest that cyclic fatty acids formed from cyclization of linolenic acid are not a major concern for human safety.

Accelerated clearance of plasma triglycerides and free fatty acids in omega3-depleted rats.

The present study aims mainly at exploring the effects of a severe depletion in polyunsaturated long-chain omega3 fatty acids upon the fate of circulating lipids. The plasma concentration and fatty acid pattern of triglycerides, diglycerides, free fatty acids, and phospholipids were measured in omega3-depleted and control rats injected intravenously one hour before sacrifice with either saline, a control medium-chain triglyceride:olive oil emulsion or a medium-chain triglyceride:fish oil emulsion recently found to rapidly increase the phospholipid content of C20:5omega3 and C22:6omega3 in different cell types. The estimated fractional removal rate of the injected triglycerides and the clearance of free fatty acids from circulation were both higher in omega3-depleted rats than in control animals. The injection of the lipid emulsions apparently inhibited intracellular lipolysis, this being least pronounced in omega3-depleted rats. The increased clearance of circulating triglycerides and unesterified fatty acids in omega3-depleted rats may favor the cellular accumulation of lipids. In turn, such an accumulation and the lesser regulatory inhibition of tissular lipolysis may match the increased clearance of circulating unesterified fatty acids and, hence, account for the lack of any significant difference in plasma unesterified fatty acid concentration between these and control animals.

Butters rich either in trans-10-C18:1 or in trans-11-C18:1 plus cis-9, trans-11 CLA differentially affect plasma lipids and aortic fatty streak in experimental atherosclerosis in rabbits.

Dairy fat contains high amounts of saturated fatty acids (FA), which are associated with cardiovascular disease (CVD) risk. Manipulation of dairy cows nutrition allows to decrease the saturated FA content of milk fat, and is associated with increases either in conjugated linoleic acid (CLA) and trans-11-C18:1 contents, or in trans-10-C18:1 content. CLA putatively exhibits beneficial properties on CVD risk, whereas trans FA are suspected to be detrimental. The present study compared the effects of a trans-10-C18:1-rich butter (T10 butter), a trans-11-C18:1+CLA-rich butter (T11-CLA butter) and a standard butter (S butter) on lipid parameters linked to the CVD risk and fatty streaks. Thirty-six White New Zealand rabbits were fed one of the three butters (12% of the diet, plus 0.2% cholesterol) for 6 (experiment 1) or 12 (experiment 2) weeks. Liver lipids, plasma lipids and lipoprotein concentrations (experiments 1 and 2) and aortic lipid deposition (experiment 2) were determined. The T10 butter increased VLDL-cholesterol compared with the two others, and total and LDL-cholesterol compared with the T11-CLA butter ( P < 0.05). The T10 butter also increased non-HDL/HDL ratio and aortic lipid deposition compared with the T11-CLA butter ( P < 0.05). The T11-CLA butter non-significantly reduced aortic lipid deposition compared with the S butter, and decreased HDL-cholesterol and increased liver triacyglycerols compared with the two other butters ( P < 0.05). These results suggest that, compared with the S butter, the T10 butter had detrimental effects on plasma lipid and lipoprotein metabolism in rabbits, whereas the T11-CLA butter was neutral or tended to reduce the aortic lipid deposition.

Adverse effects of conjugated alpha-linolenic acids (CLnA) on lipoprotein profile on experimental atherosclerosis in hamsters.

Conjugated linoleic acids (CLAs) such as rumenic acid (RA) have the potential to alter blood lipid profiles in animals and in humans. In contrast, physiological effects of conjugated α-linolenic acids (CLnAs), which concomitantly are omega-3 and conjugated fatty acids, are still unknown. The aim of this study was to evaluate the potential of CLnA to interfere in early steps of atherosclerosis by altering lipoprotein profiles and fatty streaks in the aortas. F1B hamsters were fed a control or one of the three hypercholesterolemic (HC) diets: HC-control, HC-RA (18:2 cis-9, trans-11) or HC-CLnA (CLnA: equimolar mixture of 18:3 cis-9, trans-11, cis-15 and cis-9, trans-13, cis-15) diet. In low-cholesterol control-fed hamsters, the proportion of high-density lipoprotein cholesterol (HDL-C) was around 45% while in HC-fed hamsters, HDL-C was around 10% and cholesterol was mostly (80%) carried by triglyceride-rich lipoproteins (TRL). Low-density lipoprotein (LDL) triglycerides (TGs) increased by approximately 60% in hamsters fed either HC-RA or HC-CLnA compared with HC-controls but not compared with the low-cholesterol control diet. HDL cholesterol decreased by 24% and 16% in hamsters fed HC-RA and HC-CLnA, respectively. Small dense LDL-cholesterol increased by approximately 60% in hamsters fed HC-RA and HC-CLnA compared with the HC-control group and by more than a 100% compared with hamsters on the control diet. The relative percentage of liver cholesteryl ester content increased by 88% in hamsters fed HC diets compared with the control diet. Significant differences in fatty streaks were observed between control and HC-diet-fed hamsters. However, no significant difference was observed among the HC-diet-fed hamsters. This study shows that animals fed any one of the HC diets developed an adverse lipoprotein profile compared with a normolipidic diet. Also, HC-RA or HC-CLnA diets altered lipoprotein profile compared with animals fed the HC-control diet but had no beneficial effects on atherosclerosis.

Acute in vivo administration of a fish oil-containing emulsion improves post-ischemic cardiac function in n-3-depleted rats.

A novel i.v. lipid preparation (MCT:FO) containing 80% medium chain-triacylglycerols and 20% fish oil was recently developed to rapidly replenish cell membrane phospholipids with omega 3 (n-3) polyunsaturated fatty acids (PUFA). In regard of this property, we investigated the effect of a single i.v. administration of MCT:FO on the recovery of cardiac function after ischemia in control and n-3-depleted rats. Results were compared with those obtained either with a control preparation, where FO was replaced by triolein (MCT:OO), or with saline. Saline (1 ml) or lipid preparation (also 1 ml) was injected as a bolus via the left saphenous vein. After 60 min the heart was removed and perfused for 20 min in normoxic conditions according to Langendorff. Thereafter, the heart was subjected to a 20 min zero-flow normothermic ischemia, followed by 40 min reperfusion. Cardiac mechanical and metabolic functions were monitored. In control rats, the previous administration of a lipid preparation (MCT:FO or MCT:OO) versus saline improved cardiac function during aerobic reperfusion post-ischemia. N-3-depleted rats showed decreased basal cardiac function and impaired recovery following ischemia. However, the bolus injection of MCT:FO opposed the deleterious effect of long-term n-3-deficiency and, in this respect, was superior to MCT:OO over the first 20 min of reperfusion. This novel approach to rapidly correct n-3 PUFA-deficiency might be clinically relevant and offer interesting perspectives in the management of acute ischemic accidents.

Plasmalogen metabolism-related enzymes in rat brain during aging: influence of n-3 fatty acid intake.

Plasmalogens (Pls) are phospholipids containing a vinyl-ether bond at the sn-1 position of the glycerol backbone. They represent between 1/2 and 2/3 of the ethanolamine phospholipids in the brain. During aging, the Pls content in human brain falls down. However, the role of Pls metabolism-related enzymes in the regulation of Pls levels remains to be determined. Dihydroxyacetone phosphate acyltransferase (DHAP-AT) is the enzyme involved in the first step of Pls biosynthesis. In the brain, a phospholipase A2, which selectively acts on Pls, has been isolated (Pls-PLA2s). In this work, we aimed to evaluate the impact of DHAP-AT (a key enzyme of Pls biosynthesis) and Pls-PLA2 (a specific Pls degradation enzyme) on the evolution of Pls content in the rat brain during aging. The influence of n-3 fatty acid intake was also evaluated. Littermates from two generations of n-3 deficient rats were fed an equilibrated diet containing either alpha-LNA alone or with two doses of DHA. After weaning, 3, 9 or 21 months of diet, rats were sacrificed. Enzymatic assays were performed, Pls levels were assessed and the sn-2 position of ethanolamine Pls was analyzed. DHAP-AT activity significantly increased between weaning and 3 months with a concomitant increase of brain Pls, which reached maximal levels after 9 months. Then, Pls levels and DHAP-AT activity significantly decreased while Pls-PLA2s activity significantly increased. Dietary n-3 fatty acids had no effect on DHAP-AT activity and on Pls levels. In conclusion, the increase of brain Pls content in the first part of the life may be related to the high increase of DHAP-AT activity, probably stimulated by DHA. In aged animals, the decrease of Pls levels may mainly be caused to an increase of their degradation by Pls-PLA2. Dietary DHA may not oppose the physiologic aging.

Effects of aging and dietary n-3 fatty acids on rat brain phospholipids: focus on plasmalogens.

The aging brain undergoes modifications in the lipid composition of cell membranes and especially in plasmalogens. These phospholipids represent between one-half and two-thirds of the ethanolamine phospholipids in the brain. They are known to facilitate membrane fusion and act as endogenous antioxidants. During normal aging and in some pathological conditions, plasmalogen and DHA levels fall. In this context, we aimed to evaluate the influence of n-3 FA intake on plasmalogens in the brain during aging. Littermates from two generations of n-3-deficient rats were fed an n-3-deficient diet or an equilibrated diet containing either alpha-linolenic acid alone (alpha-LNA) or with two doses of DHA (0.3 or 0.6% w/w). After weaning, 9 mon of diet, or 21 mon of diet, plasmalogen levels were assessed, and the sn-2 substitutions of plasmenylethanolamines were analyzed in the cortex, striatum, and hippocampus. Our results showed that plasmalogen contents were not influenced by the diet. Plasmalogen levels were significantly decreased in aged rats compared with adults, whereas DHA levels increased in the hippocampus and remained stable in the cortex and striatum. DHA levels were significantly and similarly increased in total phospholipids and especially in plasmenylethanolamines after 9 mon of diet containing alpha-LNA alone or combined with DHA. This study showed that each structure sustained specific age-induced modifications. Dietary n-3 FA may not oppose the physiological decrease in brain plasmalogen levels during aging. Moreover, alpha-LNA appears to be equally as potent as preformed DHA at replacing DHA in the brain of our rat model.

Hepatic steatosis is not due to impaired fatty acid oxidation capacities in C57BL/6J mice fed the conjugated trans-10,cis-12-isomer of linoleic acid.

Decreased body fat mass and liver steatosis have been reported in mice fed diets containing the conjugated linoleic acid trans-10,cis-12-C18:2 (CLA2), but not in those fed diets containing cis-9,trans-11-C18:2 (CLA1). Because the decrease in fatty acid (FA) oxidation may cause fat accumulation, we questioned whether the effects of both CLAs on enzyme activities and mRNA expression were related to liver FA oxidation. To address this question, 7-wk-old male C57BL/6J mice were fed for 4 wk a diet supplemented with 1% CLA1, CLA2, or cis-9-C18:1 (control) esterified as triacylglycerols. In CLA2-fed mice, the proportions of CLA2 in the total FA of liver lipids were substantially lower than those of CLA1 in mice fed CLA1. The mitochondrial protein content per total liver was about 56% greater in CLA2-fed mice than in CLA1-fed mice and controls. Mitochondrial carnitine palmitoyltransferase I (CPT I) and carnitine-dependent palmitate oxidation activities were also significantly greater in CLA2-fed mice than in the two other groups. The amounts of malonyl-CoA per gram of liver and the sensitivity of CPT I to malonyl-CoA inhibition were greater in both groups of CLA-fed mice than in the controls. L-CPT I mRNA expression doubled in CLA2-fed mice and was 3 and 2 times greater for M-CPT I in the CLA1 and CLA2 groups, respectively, compared with controls. Peroxisomal FA oxidation-related activities and acyl-CoA oxidase mRNA expression were increased in CLA1-fed mice, and to a larger extent in CLA2-fed mice, relative to controls. These data indicate that FA oxidation capacities were increased in mice fed CLA2, but were likely depressed in vivo through malonyl-CoA inhibition.

The position of rumenic acid on triacylglycerols alters its bioavailability in rats.

The metabolic fate of rumenic acid (9cis,11trans-octadecenoic acid) related to its position on the glycerol moiety has not yet been studied. In the present work, synthetic triacylglycerols (TAG) esterified with oleic and rumenic acids were prepared. Rats were force-fed synthetic dioleyl monorumenyl glycerol with (14)C labeled rumenic acid in the internal (sn-2) or in the external position (sn-1 or sn-3). Rats were then placed in metabolic cages for 16 h. At the end of the experiment, the radioactivity in tissues, carcass and expired CO(2) was measured. Rumenic acid that was esterified at the external positions on the TAG was better absorbed and oxidized to a greater extent than when esterified at the internal position. The fatty acid from the 2-TAG form was also better incorporated into the rat carcass. In the liver, rumenic acid appeared mainly in TAG (50%) and to a lesser extent in phospholipids (33%) whatever its dietary form. Moreover, analyses of lipids from Camembert cheese and butter revealed that rumenic acid was located mainly on the sn-1 or sn-3 positions (74%). Taken together, these data suggest that rumenic acid from dairy fat may be well absorbed and used extensively for energy production.

Effect of conjugated FA on feed intake, body composition, and liver FA in mice.

CLA is a generic term describing different isomers of linoleic acid with two conjugated double bonds. Various metabolic effects have been demonstrated following administration of CLA, including a change in body composition in animals. However, the effects of pure CLA isomers are not fully understood. In addition, conjugated octadecatrienoic acids such as calendic acid have not been extensively investigated. In this study, male and female ICR mice were fed pure CLA isomers (cis9,trans11 or trans10,cis12) or calendic acid (trans8,trans10,cis12) as their ethyl esters for 6 wk. Body protein content was significantly increased after feeding CLA isomers, either as pure isomers or as a mixture. Calendic acid significantly decreased body fat content in males. CLA (pure isomers or a mixture) significantly decreased body fat in both males and females, with the trans10,cis12 isomer being the most effective. The effect of the cis9,trans11 isomer was more pronounced in females than in males. It was concluded that the trans10,cis12 CLA isomer was mainly responsible for the decrease in fat content in mice, without a significant modification of feed efficiency, and that it was more effective than calendic acid.

Might analysis, synthesis and metabolism of CLA contribute to explain the biological effects of CLA?

Conjugated Linoleic Acids (CLA) are of great interest for analysts since techniques have been developed to determine the dietary occurrence of CLA with a good accuracy. CLA is found in animal products from ruminant sources as the result of biohydrogenation of polyunsaturated fatty acids in the rumen and as the consequence of the delta-9 desaturation of vaccenic acid in animal tissues. CLA can also be obtained in the laboratory by isomerisation of linoleic acid or by total chemical synthesis. While the "natural" isomer is rumenic acid (9c,11t-18:2), synthetic mixtures contain mainly two isomers: the 9c,11t- and the 10t,12c-18:2. Although CLA have been shown to be metabolized into desaturated and chain elongated products, it remains unclear whether these so-formed conjugated metabolites may be involved in the effects of CLA on fatty acid metabolism. Experiments carried out on animal models with CLA have shown different health benefits: anticarcinogenic, antiatherosclerotic effects, modulation of body composition , the "natural" CLA (9c,11t-18:2) being closely related to the protection against cancer and the 10t,12c-18:2 to the reduction of the fat mass. Nevertheless, recent findings have suggested adverse effects in mice. Most of the studies carried out on humans concern the influence of CLA on body composition and its possible inverse association with cancer. Since the results are still controversial and since very few data dealing with the safety of using CLA in long term feeding studies have so far been published, further works are warranted to consider the benefits of CLA for humans.

Stereoselective synthesis of (6Z,10E,12Z)-octadeca-6,10,12-trienoic acid, (8Z,12E,14Z)-eicosa-8,12,14-trienoic acid, and their [1-14C]-radiolabeled analogs.

To study the metabolic fate of conjugated linoleic acid isomers, we synthesized, in seven steps, from 1-heptyne, (6Z,10E,12Z)-octadeca-6,10,12-trienoic acid, (8Z,12E,14Z)-eicosa-8,12,14-trienoic acid, and their [1-(14)C]-analogs. In the case of (6Z,10E,12Z)-octadecatrienoic acid, a series of palladium-catalyzed cross-coupling reactions between 1-heptyne and (E)-1,2-dichloro-ethene, a coupling reaction with a Grignard reagent and cleavage of the dioxolane gave (E)-dodec-4-en-6-ynal 3. Stereoselective Wittig reaction between aldehyde 3 and triphenyl-[5-(tetrahydro-pyran-2-yloxy)-pentyl]-phosphonium provided a dienyne. Stereocontrolled reduction of the triple bond and replacement of the tetrahydropyranyl group by a bromine gave (5Z,9E,11Z)-1-bromo-heptadeca-5,9,11-triene 10. Formation of the alkenyl lithium derivative and carbonation with CO(2) furnished (6Z,10E,12Z)-octadecatrienoic acid. (8Z,12E,14Z)-eicosa-8,12,14-trienoic acid was obtained by the same route but using triphenyl-[5-(tetrahydro-pyran-2-yloxy)-heptyl]-phosphonium iodide for the Wittig reaction. [1-(14)C]-analogs were obtained from the bromides by carbonation with (14)CO2. In all cases, chemical or radiochemical purities were found to be better than 95% after purification by flash chromatography on silica gel (>99% after additional purification by RP-HPLC). Metabolism studies in animals are in progress.

In vitro desaturation and elongation of rumenic acid by rat liver microsomes.

Various nutritional studies on CLA, a mixture of isomers of linoleic acid, have reported the occurrence of conjugated long-chain PUFA after feeding experimental animals with rumenic acid, 9c,11t-18:2, the major CLA isomer, probably as a result of successive desaturation and chain elongation. In the present work, in vitro studies were carried out to obtain information on the conversion of rumenic acid. Experiments were first focused on the in vitro delta6-desaturation of rumenic acid, the regulatory step in the biosynthesis of long-chain n-6 PUFA. The conversion of rumenic acid was compared to that of linoleic acid (9c,12c-18:2). Isolated rat liver microsomes were incubated with radiolabeled 9c,12c-18:2 and 9c,11t-18:2 under desaturation conditions. The data indicated that [1-(14)C]9c,11t-18:2 was a poorer substrate for delta6-desaturase than [1-(14)C]9c,12c-18:2. Next, in vitro elongation of 6c,9c,11t-18:3 and 6c,9c,12c-18:3 (gamma-linolenic acid) was investigated in rat liver microsomes. Under elongation conditions, [1-(14)C]6c,9c,11t-18:3 was 1.5-fold better converted into [3-(14)C]8c,11c,13t-20:3 than [1-(14)C]6c,9c,12c-18:3 into [3-(14)C]8c,11c,14c-20:3. Finally, in vitro delta5-desaturation of 8c,11c,13t-20:3 compared to 8c,11c,14c-20:3 was investigated. The conversion level of [1-(14)C]8c,11c,13t-20:3 into [1-(14)C]5c,8c,11c,13t-20:4 was 10 times lower than that of [1-(14)C]8c,11c,14c-20:3 into [1-(14)C]5c,8c,11c,14c-20:4 at low substrate concentrations and 4 times lower at the saturating substrate level, suggesting that conjugated 20:3 is a poor substrate for the delta5-desaturase.

Synthesis of (6Z,9Z,11E)-octadecatrienoic and (8Z,11Z,13E)-eicosatrienoic acids and their [1-(14)C]-radiolabeled analogs.

In order to study the metabolic pathway and the physiological effects of 9c,11t-18:2 (major isomer of conjugated linoleic acid) and its C(18:3) and C(20:3) metabolites, 6c,9c,11t-18:3 and 8c,11c,13t-20:3 and their [1-(14)C]-radiolabeled analogs were prepared stereoselectively by total synthesis. The 8c,11c,13t-20:3 was obtained in 11 steps. The synthesis involves a highly stereoselective Wittig reaction between 3-(t-butyldiphenylsilyloxy)propanal and the ylide of 7-(2-tetrahydropyranyloxy)heptanylphosphonium salt which gave (3Z)-1-(t-butyldiphenylsilyloxy)-10-(2-tetrahydropyranyloxy)dec-3-ene in a first step. Then the t-butyldiphenylsilyl derivative was deprotected selectively and the resulting alcohol function was converted via a bromide into a phosphonium salt. The second stereoselective Wittig condensation between the phosphonium salt and commercial (2E)-non-2-enal under cis-olefinic conditions using Lithium hexamethyldisilazide as base afforded the (7Z,10Z,12E)-1-(2-tetrahydropyranyloxy)nonadeca-7,10,12-triene in a very good isomeric purity. The intermediate product was brominated and transformed by reaction with magnesium into Grignard reagent, which was one-carbon elongated by unlabeled or labeled carbon dioxide to obtain the 8c,11c,13t-20:3 in good isomeric purity (95%) and high radiochemical purity for its [1-(14)C]-radiolabeled analog (99%). 6c,9c,11t-18:3 was synthesized in a similar way by using 5-(2-tetrahydropyranyloxy)pentanylphosphonium salt in place of 7-(2-tetrahydropyranyloxy)heptanylphosphonium salt in a first step. Other reactions were unchanged and products were obtained in similar yields. Similar to 8c,11c,13t-20:3, the 6c,9c,11t-18:3 was obtained in a very good isomeric purity (95%) and its [1-(14)C]-radiolabeled analog in a high radiochemical purity (95%).

The effect of conjugated linoleic acid isomers on fatty acid profiles of liver and adipose tissues and their conversion to isomers of 16:2 and 18:3 conjugated fatty acids in rats.

Conjugated linoleic acid (CLA) is a collective term that describes different isomers of linoleic acid with conjugated double bonds. Although the main dietary isomer is 9cis,11trans-18:2, which is present in dairy products and ruminant fat, the biological effects of CLA generally have been studied using mixtures in which the 9cis,11trans- and the 10trans,12cis-18:2 were present at similar levels. In the present work, we have studied the impact of each isomer (9cis,11 trans- and 10trans,12cis-18:2) given separately in the diet of rats for 6 wk. The 10trans,12cis-18:2 decreased the triacylglycerol content of the liver (-32%) and increased the 18:0 content at the expense of 18:1 n-9, suggesting an alteration of the delta9 desaturase activity, as was already demonstrated in vitro. This was not observed when the 9cis,11trans-18:2 was given in the diet. Moreover, the 10trans,12cis-18:2 induced an increase in the C22 polyunsaturated fatty acids in the liver lipids. The 10trans,12cis-18:2 was mainly metabolized into conjugated 16:2 and 18:3, which have been identified. The 9cis,11trans isomer was preferentially metabolized into a conjugated 20:3 isomer. Thus, the 9cis,11trans- and the 10trans,12cis-CLA isomers are metabolized differently and have distinct effects on the metabolism of polyunsaturated fatty acids in rat liver while altering liver triglyceride levels differentially.