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PubMed2006

Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal cancer cells.

The effect of conjugated linoleic acid (CLA) on peritoneal metastasis was examined by in vitro treatment of cancer cells and mouse peritoneal metastasis models. First, cell growth of MKN28 human gastric cancer cells and Colo320 human colon cancer cells was suppressed by CLA in a dose-dependent manner with an increment in apoptosis. CLA significantly inhibited invasion into type IV collagen-coated membrane of MKN28 and Colo320 cells (p < 0.05). CLA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor (PPAR)-gamma in both cell lines. BALB/c nu-nu mice were inoculated with MKN28 and Colo320 cells into their peritoneal cavity, and administrated with CLA intraperitoneally (weekly, 4 times). CLA treatment did not affect food intake or weight gain of mice. CLA treatment significantly decreased metastatic foci of both cells in the peritoneal cavity (p < 0.005). Survival rate in mice inoculated with MKN28 or Colo320 cells was significantly recovered by CLA treatment (p = 0.0025 and 0.0052, respectively). Protein production in MKN28 and Colo320 cells treated with CLA showed a decrease in epidermal growth factor receptor and transforming growth factor-alpha and an increase in Bax. These findings suggest that CLA inhibits metastasis of human gastric and colon cancer cells.

Animals↗
PubMed2003

Activation of PPAR gamma in colon tumor cell lines by oxidized metabolites of linoleic acid, endogenous ligands for PPAR gamma.

The nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) gamma plays an important role in the differentiation of intestinal cells and other tissues. Real-time PCR examination of PPAR mRNA for gamma1, gamma2 and gamma3, in Caco-2 and HCT-116 colon cell lines showed that gamma3 is the most abundant message in both lines. Treatment of Caco-2 cells with sodium butyrate, which induces cell differentiation, also leads to an increase in all three PPAR mRNAs. In contrast, treatment of HCT-116 cells with sodium butyrate, which does not lead to differentiation of these cells, causes a decrease in the amount of all three PPAR mRNAs. Furthermore, the amount of PPAR mRNA is greater in Caco-2 cells than in HCT-116 cells at all times examined. As several oxidative metabolites of linoleic acid, including 13-hydroxyoctadecadienoic acid (13-HODE) and 13-oxooctadecadienoic acid (13-OXO) have been shown to bind PPAR, and there is a strong positive correlation between enzymes for metabolism of linoleate oxidation products, intestinal cell differentiation and the distribution of PPAR, we also performed a detailed investigation of the activation of PPAR gamma by 13-HODE and 13-OXO. For these experiments, Caco-2 and HCT-116 cells were transfected with constructs containing PPAR gamma1 or gamma2 then a PPRE-luc reporter construct. Exposure of transfected cells to micromolar concentrations of 13-HODE or 13-OXO produced concentration-dependent increases in luciferase activity. In addition, the two linoleate metabolites activate endogenous PPAR in these cell lines transfected with only PPRE-luc. The data substantiate the contention that oxidation products of linoleic acid are metabolically produced endogenous ligands for PPAR gamma and that PPAR gamma plays an important role in the differentiation of intestinal cells.

Base Sequence↗
PubMed2002

Antioxidant effects of resveratrol and its analogues against the free-radical-induced peroxidation of linoleic acid in micelles.

The antioxidant effect of resveratrol (3,4',5-trihydroxy-trans-stilbene) and its analogues, that is, 4-hydroxy-trans-stilbene (4-HS), 3,5-dihydroxy-trans-stilbene (3,5-DHS), 4,4'-dihydroxy-trans-stilbene (4,4'-DHS), 3,4-dihydroxy-trans-stilbene (3,4-DHS), 3,4,5-trihydroxy-trans-stilbene (3,4,5-THS) and 3,4,4'-trihydroxy-trans-stilbene (3,4,4'-THS), against the peroxidation of linoleic acid has been studied in sodium dodecyl sulfate (SDS) and cetyltrimethyl ammonium bromide (CTAB) micelles. The peroxidation was initiated thermally by a water-soluble azo initiator 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH), and the reaction kinetics were studied by monitoring the formation of linoleic acid hydroperoxides. The synergistic antioxidant effect of these compounds with alpha-tocopherol (vitamin E) was also studied by following the decay kinetics of alpha-tocopherol and the reaction intermediate, the alpha-tocopheroxyl radical. Kinetic analysis of the antioxidant process demonstrates that these compounds are effective antioxidants in micelles used either alone or in combination with alpha-tocopherol. The antioxidative action involves trapping the propagating lipid peroxyl radical and reducing the alpha-tocopheroxyl radical to regenerate alpha-tocopherol. It was found that the antioxidant activity of resveratrol analogues depends significantly on the position of the hydroxyl groups, the oxidation potential of the molecule and the reaction medium. Molecules with ortho-dihydroxyl and/or para-hydroxyl functionalities possess high activity.

Antioxidants↗
PubMed2006

Descriptive flavor analysis of bacon and pork loin from lean-genotype gilts fed conjugated linoleic acid and supplemental fat.

This study evaluated the combined effects of dietary CLA and supplemental fat (SF) source on organoleptic characteristics of bacon and pork loin samples in lean-genotype gilts (n = 144). Gilts (49.3 kg of BW) were randomly assigned to a 3 x 2 factorial design, consisting of SF [0% SF, 4% yellow grease (YG), or 4% tallow] and linoleic acid (LA; 1% corn oil or 1% CLA). Animals were slaughtered (113 kg) after a feeding period of 47 d. A trained sensory panel (n = 6 members) developed a flavor profile on commercially cured bacon samples (12 descriptors) and center-cut, boneless, pork loin chops (18 descriptors, using a 14-point, universal intensity scale). Bacon samples from pigs fed 4% SF were considered to have a sweeter flavor (4.07 +/- 0.07) than those fed 0% SF (3.89 +/- 0.07; P < 0.04). The intensity of salty flavor was greater in bacon samples from pigs fed LA (6.18 +/- 0.09) compared with those fed CLA (5.86 +/- 0.10; P < 0.04). The intensity of salty aftertaste of bacon was greater when LA was combined with YG (5.21 +/- 0.14; P < 0.07) or tallow (5.44 +/- 0.14; P < 0.01) than for LA alone (4.85 +/- 0.14, but SF combined with CLA was not different from CLA alone (fat x LA; P < 0.02). Sour flavor intensity tended to be lower in loin samples from pigs fed CLA than for those fed LA (1.60 vs. 1.73 +/- 0.06; P < 0.09). Samples from animals fed 4% tallow tended to have lower (P < 0.09) notes of astringent aftertaste (1.42 +/- 0.08) compared with those fed 0% SF (1.62 +/- 0.09) or 4% YG (1.66 +/- 0.09). Overall, the flavor differences for bacon and loin samples were minimal, with most means differing by 1 point or less on the 14-point intensity scale. The sensory panel results indicate consumer acceptance of bacon and pork products from pigs fed CLA will not likely differ from commodity pork products.

Animal Feed↗
PubMed2001

Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression.

Conjugated linoleic acid (CLA) isomers have a number of beneficial health effects, as shown in biomedical studies with animal models. Previously, we reported that a mixture of CLA isomers improved glucose tolerance in ZDF rats and activated peroxisome proliferator-activated receptor (PPAR)-gamma response elements in vitro. Here, our aim was to elucidate the effect(s) of specific CLA isomers on whole-body glucose tolerance, insulin action in skeletal muscle, and expression of genes important in glucose and lipid metabolism. ZDF rats were fed either a control diet (CON), one of two CLA supplemented diets (1.5% CLA) containing differing isoforms of CLA (47% c9,t11; 47.9% c10,t12, 50:50; or 91% c9,t11, c9,t11 isomers), or were pair-fed CON diet to match the intake of 50:50. The 50:50 diet reduced adiposity and improved glucose tolerance compared with all other ZDF treatments. Insulin-stimulated glucose transport and glycogen synthase activity in skeletal muscle were improved with 50:50 compared with all other treatments. Neither phosphatidlyinositol 3-kinase activity nor Akt activity in muscle was affected by treatment. Uncoupling protein 2 in muscle and adipose tissue was upregulated by c9,t11 and 50:50 compared with ZDF controls. PPAR-gamma mRNA was downregulated in liver of c9,t11 and pair-fed ZDF rats. Thus, the improved glucose tolerance in 50:50 rats is attributable to, at least in part, improved insulin action in muscle, and CLA effects cannot be explained simply by reduced food intake.

Adipose Tissue↗
PubMed2001

Comparison of methylation procedures for conjugated linoleic acid and artifact formation by commercial (trimethylsilyl) diazomethane.

Four different methods for methylating conjugated linoleic acid (CLA) were compared. The HCl/MeOH and BF(3)/MeOH methods were tested under different time and temperature combinations. Increasing temperature and/or incubation time for either method decreased the cis-9,trans-11 and trans-10,cis-12 isomers, but trans-9,trans-11/trans-10,trans-12 isomers and artifacts (allylic methoxide) were increased. In addition, the triacylglyceride form of CLA was tested using the above methods and NaOMe at various temperatures for 20 min. The NaOMe did not generate methoxy artifacts. However, there were impurities in GC after methylation with NaOMe as well as with BF(3)/MeOH. The (trimethylsilyl)diazomethane method, which is a mild and easy alternative, was tested. Free forms of fatty acids were easily, but not completely, methylated by this method. Also, the method generated artifacts (trimethylsilyl CLA esters) and impurities (trimethylsilyl) that would interfere with short-chain fatty-acid analysis by GC.

Artifacts↗
PubMed2000

Nadolol inhibits reactive oxygen species generation by leukocytes and linoleic acid oxidation.

We studied the effect of short-term nadolol administration on the reactive oxygen species (ROS) generation by polymorphonuclear leukocytes and mononuclear cells in 8 normal subjects. At a oral dose of 40 mg/day for 5 days, nadolol produced a decrease in the ROS generation by leukocytes. ROS generation by polymorphonuclear leukocytes decreased by 38% from 134 +/- 44 mV at baseline to 83 +/- 34 mV after 5 days (p = 0.005), and ROS generation by mononuclear cells decreased by 33% from 174 +/- 69 mV at baseline to 117 +/- 55 mV after 5 days (p = 0.015). There was also a significant reduction in linoleic acid oxidation as reflected by the lower levels of 9- and 13- hydroxy-octadecadienoic acid after 5 days. There was no change in the plasma thiobarbituric acid-reacting substances, a less sensitive index of oxidative damage to lipids. There was also no significant change in the levels of metatyrosine and orthotyrosine, which are known indexes of oxidative damage to amino acids and proteins. The absence of a significant change in metatyrosine, orthotyrosine, and thiobarbituric acid-reacting substances may reflect the short duration of nadolol administration and the decreased ROS load. Because ROS may induce lipid peroxidation, this inhibitory effect of nadolol on ROS generation by leukocytes and linoleic acid oxidation may inhibit low-density lipoprotein oxidation and thus atherogenesis. This effect may partly explain the favorable outcomes observed in patients with coronary artery disease on long-term beta-blocker therapy.

Administration, Oral↗
PubMed2006

Fatty acid composition of ruminal bacteria and protozoa, with emphasis on conjugated linoleic acid, vaccenic acid, and odd-chain and branched-chain fatty acids.

Knowledge of the fatty acid profile of microbial lipids is of great nutritional importance to the animals and, subsequently, their products. This study was conducted to examine the fatty acid profiles of mixed rumen bacteria and protozoa. Bacterial and protozoal cells were isolated by differential centrifugation of rumen contents. The main fatty acids were palmitic (16:0) and stearic (18:0) in both the bacterial and protozoal fractions. Palmitic acid was 74% greater in the protozoal fatty acids than in the bacterial fatty acids, whereas bacteria had 2.25-times greater stearic acid (18:0) proportions compared with protozoa. The total odd-chain plus branched-chain fatty acids were 16.5% of bacterial fatty acids and 11.0% of protozoal fatty acids. The anteiso-17:0 proportions in bacterial and protozoal fatty acids were 1.4 and 2.9%, respectively. The most abundant trans-18:1 isomer, vaccenic acid (18:1 trans-11), was 6.6% of total fatty acids in protozoa and 2.0% of total fatty acids in bacteria. The cis-9, trans-11 CLA was 8.6-times greater in the protozoal fraction (1.32% of total fatty acids) than in the bacterial fraction (0.15%). These results suggest that the presence of protozoa in the rumen may increase the supply of CLA and other unsaturated fatty acids for lower gut absorption by ruminants.

Animals↗
PubMed2001

Total body electrical conductivity (TOBEC) measurement of compositional differences in hams, loins, and bellies from conjugated linoleic acid (CLA)-fed stress-genotype pigs.

This study was designed to observe the effects of conjugated linoleic acid (CLA) supplementation on lean content of pork carcass primal cuts (hams, loins, and bellies) and to determine the ability of total body electrical conductivity (TOBEC) to predict lean content. A total of 64 crossbred growing-finishing barrows were placed on a control (soybean oil) or CLA (0.75%) diet at an average weight of 40 kg. Pigs were penned in pairs according to diet and stress genotype (negative, carrier, and positive) and slaughtered at 115 kg. Stress genotype was included because of known variations in lean content. Hams (IMPS 401A; n = 64), loins (IMPS 410; n = 24), and bellies (IMPS 408; n = 63) were fabricated from carcasses at 24 h postmortem and scanned for electromagnetic (EM) absorption by a MQ-25 EM scanner. Each wholesale cut was scanned in triplicate at 2.5 MHz to yield a peak mean average (PMA) value then separated into lean, fat, bone, and skin components. Bellies were skinned prior to scanning then subjected to a belly bar firmness test before dissection. Supplementation with CLA had no effect (P > 0.05) on lean ham composition. Regression analysis was used for lean weight prediction using primal weight and PMA value as predictors. Lean content prediction of hams by TOBEC resulted in an R2 of 0.80. Loins from CLA-supplemented pigs exhibited increased lean weight (P < 0.05) and PMA values (P < 0.05) compared to controls. Lean prediction of loins by TOBEC resulted in an R2 of 0.66. Bellies from CLA-supplemented pigs had a higher percentage of moisture (P < 0.03) and protein (P < 0.01) and decreased percentage of lipid (P < 0.01). The R2 values from the regression analysis predicting protein, moisture, protein + moisture, and fat-free soft tissue composition of the skinless bellies were 0.67, 0.68, 0.71, and 0.78, respectively.

Animals↗
PubMed2005

Comparison of calcium salts and formaldehyde-protected conjugated linoleic Acid in inducing milk fat depression.

Abomasal infusion studies have shown that trans-10, cis-12 conjugated linoleic acid (CLA) decreases milk fat synthesis. However, supplements of CLA must avoid rumen biohydrogenation for this technology to be applied to ruminants. Rumen protection methods would reduce CLA metabolism in the rumen and increase its supply to the small intestine. Our objective was to compare the efficacy of 2 forms of rumen-protected CLA at inducing milk fat depression. Three mid to late lactation Holstein cows each fitted with a rumen fistula were used in a 3 x 3 Latin square design. Treatments were: 1) control, 2) calcium salts of CLA (Ca-CLA), and 3) formaldehyde-protected CLA (FP-CLA). Supplements were designed to provide 10 g/d of trans-10, cis-12 CLA and were administered intraruminally once per day to ensure exact delivery of amount. Both CLA treatments substantially reduced milk fat yield and content compared with control, with the reductions in milk fat yield averaging 34% for the Ca-CLA treatment and 44% for the FP-CLA treatment. In contrast, milk yield, milk protein yield, and dry matter intake were unaltered by CLA treatment. Efficiency of transfer of trans-10, cis-12 CLA from the supplement into milk fat was 3.2 and 7.0% for Ca-CLA and FP-CLA, respectively. These values are much lower than transfer efficiencies reported for abomasally infused CLA, suggesting that much of the trans-10, cis-12 CLA present in the 2 formulations was biohydrogenated in the rumen. Overall, the extent of the reduction in milk fat yield indicates that both protection formulations are acceptable methods for the formulation of CLA supplements to induce milk fat depression in lactating dairy cows.

Animals↗
PubMed2007

Effects of varying doses of supplemental conjugated linoleic acid on production and energetic variables during the transition period.

Supplementing a high dose of dietary conjugated linoleic acid (CLA) inhibits milk fat synthesis in dairy cows immediately postpartum. During negative net energy balance (EBAL), it appears that moderate CLA-induced milk fat depression causes a positive response in milk yield; however, as milk fat depression becomes more severe, the milk yield response diminishes. Multiparous Holstein cows (n = 31) were randomly assigned to 1 of 3 treatments beginning 9 +/- 6 d before expected calving and ceased at 40 d in milk (DIM): 1) 578 g/d of a rumen-inert (RI) palm fatty acid distillate (control), 2) 600 g/d of RI-CLA for the entire trial period (CLA-1), and 3) 600 g/d of RI-CLA until 10 DIM followed by 200 g/d for the remainder of the trial (CLA-2). Each dose provided equal amounts of fatty acids by replacing and balancing each treatment with a RI palm fatty acid distillate. Doses provided a total of 522 g of fatty acids/ d and 0, 174, or 58 (depending upon DIM) g of CLA (mixed isomers)/d. To improve palatability, doses were mixed with 600 g/d of dried molasses; one-half of the supplement was fed at 0800 h, and the remainder at 1900 h. Individual milk yield, dry matter intake, and body weight were recorded daily and milk composition determined every other day. There was no overall CLA effect on either the content or yield of milk protein or lactose. Both CLA treatments decreased overall milk fat content (26.0 and 18.3%) and yield (22.5 and 17.3%) with CLA-induced milk fat depression becoming significant by d 8. The CLA-induced milk fat depression increased in magnitude with progressing DIM until reaching a plateau on d 18 for CLA-1 (43%) and on d 14 for CLA-2 (33%), although neither milk fat trans-10, cis-12 CLA content (1.8 mg/g) nor its transfer efficiency (6.3%) changed over time. Treatments had no effect on overall dry matter intake or milk yield, but there was a treatment x time interaction for milk production, as cows fed either CLA treatment had increased milk yield after the second week of lactation. Cows fed either CLA treatment had a significant improvement in overall EBAL (-5.1 vs. -1.8 Mcal/d), a decrease in nonesterified fatty acid levels (12%), and an increase in glucose levels (11%). A dietary supplement containing trans-10, cis-12 CLA markedly improves EBAL and bioenergetic variables and increases milk yield in the total mixed ration-fed transitioning dairy cow.

Animals↗
PubMed1984

Site-specific cleavage of double-strand DNA by hydroperoxide of linoleic acid.

The breakage of double-strand (ds) DNA by 13-L-hydroperoxy-cis-9,trans-11-octadecadienoic acid (LAHPO) was investigated by agarose gel electrophoresis of supercoiled pBR322 DNA and the site of cleavage on the DNA molecule was determined by the method of DNA sequence analysis using 3'-end and 5'-end-labeled DNA fragments as substrates. LAHPO caused cleavage at the position of guanine nucleotide in dsDNA. LAHPO caused dsDNA breaks at specific sites, but linoleic acid (LA) and 13-L-hydroxy-cis-9,trans-11-octadecadienoic acid (LAHO) have no such effects on dsDNA. The active oxygen atom of the hydroperoxy group of LAHPO was perhaps responsible for the site-specific cleavage of dsDNA.

Animals↗
PubMed1991

Role of dietary oleic acid in linoleic acid-enhanced metastasis of a mouse mammary tumor.

We have previously shown that a high fat diet (20% w/w) containing 12% linoleic acid (18:2) can significantly increase the metastasis of mammary tumor cells when compared with high fat diets that contain 8% or less 18:2 with a constant level of oleic acid (18:1). This effect may have been due to an alteration of eicosanoid metabolism because the cyclooxygenase inhibitor, indomethacin, abolished the increase. Because 18:1 may interfere with the metabolism of 18:2 to 20:4, we have now tested whether the 18:1 that supplements the 18:2 diet can have an effect on spontaneous or experimental metastasis of the line 4526 murine mammary tumor. For this, six 20% fat diets were formulated with 1%, 6%, and 12% 18:2 and either high or low levels of 18:1. Our results indicate that the amount of select fatty acids other than 18:2 at 12% has no significant effect on mouse growth, tumor growth, or tumor latency. When spontaneous metastatic burden was calculated, no significant differences between mice fed diets containing 1% and 6% 18:2 were observed. However, 4 to 5 times more of a metastatic burden was observed in mice fed diets containing 12% 18:2. No significant differences were observed between high and low 18:1 diets when the 18:2 content was 1 or 12%. However, at 6% 18:2, 18:1 significantly decreased metastatic burden. When experimental metastasis was assessed, relatively low levels of surface lung nodules were observed at 1% and 6% 18:2, but significantly higher levels were observed at 12% 18:2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Evidence that the anti-obesity effect of conjugated linoleic acid is independent of effects on stearoyl-CoA desaturase1 expression and enzyme activity.

The trans-10,cis-12 isomer of conjugated linoleic acid (CLA) reduces body fat gain in animals and inhibits stearoyl-CoA desaturase (SCD) activity in 3T3-L1 adipocytes. To test whether CLA's body fat reduction is mediated by SCD1, wild-type and SCD1-null mice were fed diet supplemented with 0.2% trans-10,cis-12 (t10c12) CLA for 4 weeks. The t10c12 CLA-supplemented diet significantly reduced body fat mass in both wild type and SCD1-null mice. Similarly, t10c12 CLA diet decreased blood triglyceride and free fatty acid levels regardless of SCD1 genotypes. Mice fed t10c12 CLA exhibited increased mRNA expression of fatty acid synthase and uncoupling protein 2 in both genotypes. Taken together, the effects of t10c12 CLA on reduction of body fat gain, blood parameters, and mRNA expression in both SCD1-null mice and wild-type mice were similar, indicating that the anti-obesity effect of t10c12 CLA may be independent of the effects of this CLA isomer on SCD1 gene expression and enzyme activity.

3-Hydroxybutyric Acid↗
PubMed2003

Conjugated linoleic acid content in breast adipose tissue of breast cancer patients and the risk of metastasis.

The association between the level of conjugated linoleic acid (CLA) in breast adipose tissue at the time of diagnosis and the subsequent development of metastasis was examined in a cohort of 209 patients presenting with an initially localized breast cancer. CLA level in breast adipose tissue was used as a qualitative biomarker of its past dietary intake. Biopsies of adipose tissue were obtained at the time of initial surgery. A CLA-enriched fraction was prepared by high performance liquid chromatography and CLA measured as a percentage of total fatty acids, using capillary gas chromatography. Mean CLA level was low (0.44% of total fatty acids) and the range between patients was narrow (0.19-0.85). With a median follow-up time of 7.5 yr, 45 patients developed metastases. A Cox proportional hazard regression model was used to identify prognostic factors. We did not find any significant association between CLA level in adipose fat and either the prognostic factor (tumor size, nodal status, histoprognostic grade, mitotic index, and estrogen or progesterone receptors) or the risk of metastasis or death. We concluded that CLA are unlikely to be involved in survivorship. However, the hypothesis that a higher intake of CLA might have a protective effect on the risk of metastasis cannot be ruled out from these data, since the level of CLA in breast cancer patients' adipose tissue is likely to be too low and the range of CLA distribution too narrow for any protection to be detectable.

Adipose Tissue↗
PubMed1999

The effect of conjugated linoleic acid on the antioxidant enzyme defense system in rat hepatocytes.

Short-term effects of physiological concentrations of conjugated linoleic acid (CLA) on membrane integrity, metabolic function, cellular lipid composition, lipid peroxidation, and antioxidant enzymes were examined using rat hepatocyte suspension cultures. Incubation with CLA (5-20 ppm) for 3 h decreased the ability of hepatocyte plasma membranes to exclude trypan blue by approximately 25%, and caused leakage of cytosolic lactate dehydrogenase (LDH) into the medium. The significant decrease (P< 0.02) in hepatocyte viability as measured by LDH leakage during cell incubation with 10 and 20 ppm CLA was not associated with significant changes in cellular ATP content. Protein synthesis in hepatocytes was elevated (P < 0.05) in the presence of 5 and 10 ppm CLA, but at a higher concentration (20 ppm), protein synthesis was similar to that of control cells. Gluconeogenesis was maintained in cells incubated with lower concentrations of CLA (5 and 10 ppm) but was decreased (P < 0.02) at the higher concentration. Incubation with 20 ppm CLA for 3 h did not affect the specific activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol synthesis. Both cis-9,trans-11/trans-9,cis-11, and cis-10,trans-12/trans-10,cis-12 isomers of CLA were incorporated to a similar level into hepatocytes. Levels ranged from 3.9 to 4.1%, respectively, of total fatty acids in neutral lipids, and from 0.7 to 0.8%, respectively, of total fatty acids in phospholipids. Cellular lipid peroxidation remained unchanged in the presence of CLA (5-20 ppm), despite significant inhibition (P < 0.05) of superoxide dismutase. Catalase activity was maintained near control levels in the presence of 5 and 10 ppm CLA but was significantly decreased in the presence of 20 ppm CLA. Glutathione peroxidase activity was significantly decreased in the presence of 10 ppm CLA. The apparent sensitivity of the antioxidant enzyme defense system of liver cells to CLA, coupled with the lack of effect of CLA on lipid peroxidation in cells, suggests that cytotoxic effects of CLA as described by LDH leakage and decreased gluconeogenesis were not mediated by a prooxidant action in hepatocytes.

Adenosine Triphosphate↗