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To assess the oxidative metabolism of conjugated linoleic acid (CLA) isomers, rats were force-fed 1.5-2.6 MBq of [1-14C]-linoleic acid (9c,12c-18:2), -rumenic acid (9c,11t-18:2), or-10trans,12cis-18:2 (10t,12c-18:2), and 14CO2 production was monitored for 24 h. The animals were then necropsied and the radioactivity determined in different tissues. Both CLA isomers were oxidized significantly more than linoleic acid. Moreover, less radioactivity was recovered in most tissues after CLA intake than after linoleic acid intake. The substantial oxidation of CLA isomers must be considered when assessing the putative health benefits of CLA supplements.

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.

Rats were fed a fat-free diet for 2 wk. After this period, while maintaining the animals on the same diet, the rats were given intragastrically 180 mg per day of a mixture of conjugated linoleic acids (CLA) as triacylglycerols. Gas chromatography mass spectrometry (GC-MS) analyses of this mixture, as well as hydrazine reduction and GC-MS and GC-Fourier transform infrared analyses of the resulting monoenes, revealed the presence of two major isomers, the 9c,11t- and the 10t,12c-18:2 accompanied by smaller amounts of the 8t, 10c and the 11c, 13t-18:2 isomers. Minor quantities of cis,cis and trans,trans conjugated isomers also were detected. The total fatty acid methyl esters from the liver lipids were fractionated by reversed-phase high-performance liquid chromatography, and the fraction containing the 20:4 isomers was further fractionated by silver nitrate thin-layer chromatography. A band containing two 20:4 conjugated isomers was submitted to hydrazine reduction and the resulting monoenes analyzed by GC-MS as dimethyl-oxazoline derivatives. The two conjugated isomers were tentatively identified as 5c,8c, 11c, 13t-20:4 and 5c,8c,12t,14c-20:4. These could be formed by desaturation and elongation of the 9c,11t- and 10t,12c-18:2 present in the commercial CLA mixture.

Trans polyunsaturated fatty acids are formed during processing of vegetable oils such as deodorization and frying. The oxidative metabolism of linoleic and alpha-linolenic acids and of their mono-trans isomers (9cis,12trans-18:2, 9trans,12cis-18:2 and 9cis, 12cis,15trans-18:3, 9trans,12cis,15cis-18:3, respectively) was studied in fasting rats. A single dose of 18.5 MBq of each [1-14C] labelled fatty acid (260 microg) was orally given to the animals. The 14CO2 expired was monitored during 24 h. Radioactive countings of the CO2-trapping agent were performed at regular intervals up to 24 h after oral administration of the radiolabelled fatty acid. Radioactive countings were also performed on several tissues (liver, heart, brain, kidneys, sus-epidydimal fat, gastrocnemian muscle, gastrointestinal tract and carcass). The 14CO2 production 24 h after oral administration of the fatty acid ranged from 55.5% to 68.7% of the radioactivity administered for the C18:2 isomers and from 69.7% to 73.5% for the C18:3 fatty acids. From 6 to 24 h, 14CO2 recovery was significantly higher after oral administration of 9cis, 12trans-18:2 than after giving both other octadecadienoic isomers. 14C retention per gram of tissue in the liver and in the heart was significantly lower after feeding 9cis,12trans-18:2 than after administration of both other C18:2 isomers. 14C retention per gram of tissue in the muscle was significantly lower after administration of both trans C18:2 isomers compared to linoleic acid. Neither 14CO2 recoveries nor 14C retentions were significantly different after administration of the three octadecatrienoic acids. The difference observed in 14CO2 recovery within the dienes was probably not due to a higher specificity of the enzymes involved in the beta-oxidation sequence for the Delta12trans double bond, as previously reported. Indeed, due to the labelling of the fatty acids on the carboxyl end, 14C values recorded in the CO2-trapping agent were only due to the first cycle of beta-oxidation., (Copyright 1998 Elsevier Science B.V.)

Metabolism of conjugated isomers of linoleic acid (CLA) in rats was studied by feeding high quantities of CLA (180 mg/day) for six days to animals that had been reared on a fat-free diet for two weeks. After this period, animals were sacrificed and liver lipids extracted. High-performance liquid chromatography (HPLC) analyses with UV detection revealed the presence of conjugated polyunsaturated fatty acids in the total liver lipid methyl esters. After isolation by HPLC, three fatty acid metabolites were identified by gas liquid chromatography coupled with mass spectrometry as being C20:3 delta 8,12,14, C20:4 delta 5,8,12,14 and C20:4 delta 5,8,11,13. A higher quantity of C20:4 delta 5,8,12,14 compared to C20:4 delta 5,8,11,13 was observed. These must arise from the elongation and desaturation of 18:2 delta 10,12 and 18:2 delta 9,11, respectively.

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. KEY WORDS: * acetyl-CoA carboxylase * acyl-CoA oxidase * carnitine palmitoyltransferase I * malonyl-CoA * regulation