Mixture Of Conjugated Linoleic Acid Isomers Research Articles

Conjugated linoleic acid reduces visceral and ectopic lipid accumulation and insulin resistance in chronic severe hypertriacylglycerolemia

ObjectiveThe metabolic health effects of conjugated linoleic acid (CLA), which is one of the principal polyunsaturated fatty acids, are controversial and still not fully accepted. The aim of this study was to examine the effects of CLA on adiposity, ectopic lipid accumulation, and insulin-resistant states in a metabolic syndrome model of non-obese hereditary rats with hypertriacylglycerolmia (HHTg). MethodsGroups of adult male HHTg rats were fed a high-carbohydrate diet (70% sucrose) with a 2% mixture of CLA isomers, or with the same amount of sunflower oil (control group) for 2 mo. ResultsCLA supplementation decreased body weight gain (P < 0.05) and visceral adipose tissue weight (P < 0.01), and distinctively reduced serum triacylglycerols (P < 0.01) and triacylglycerol accumulation in the liver, heart, muscle, and aorta. CLA-treated rats exhibited increased insulin sensitivity in the adipose (P < 0.01), a higher release of fatty acids (P < 0.001), and increased adiponectin secretion (P < 0.01).In the skeletal muscle, CLA supplementation was associated with increased glucose oxidation (P < 0.01) and an elevated anti-inflammatory index (P < 0.05), according to phospholipid fatty acid composition. In the liver, CLA reduced the oxidized form of glutathione and elevated the activity of glutathione-dependent antioxidant enzymes. ConclusionResults suggest that CLA supplementation may protect against HHTg-induced dyslipidemia, ectopic lipid deposition, and insulin resistance. Increased glucose oxidation in the skeletal muscle as well as adiponectin secretion may play a role in the mechanism of the CLA action. Results suggest that CLA could reduce the negative consequences of HHTg and metabolic syndrome.

Synthesis and Cytotoxic Activity of New Betulin and Betulinic Acid Esters with Conjugated Linoleic Acid (CLA)

The synthesis of new ester derivatives of betulin (3a-c) and betulinic acid (4) with conjugated linoleic acid isomers (CLA; in a mixture of 43.4% 9c, 11t; 49.5% 10t, 12c; 7.1% other isomers) is presented. Esterification was carried out with N,N'-dicyclohexylcarbodiimide (DCC) as the coupling agent in the presence of 4-dimethylamino-pyridine (DMAP) in dichloromethane (or pyridine). The in vitro cytotoxic effect of betulin (1), betulinic acid (2), a mixture of CLA isomers and their derivatives (3a-c, 4) was examined using the MTT assay against four cancer cell lines (P388, CEM/C2, CCRF/CEM and HL-60) and the SRB assay on the HT-29 cell line. Ester 4 was the most active among the esters synthesized against the CEM/C2 cell line with an ID50 value 16.9 +/- 6.5 microg/mL. Betulin (1), betulinic acid (2) and CLA were the most active agents against the cancer cell lines studied.

Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice

The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. Young male mice were fed three combinations of fatty acids at three doses (0.06%, 0.2%, and 0.6%, w/w) incorporated into AIN76 diets for 7 weeks. The types of fatty acids were linoleic acid (control), an equal mixture of trans-10, cis-12 (10,12) CLA plus linoleic acid, and an equal isomer mixture of 10,12 plus cis-9, trans-11 (9,11) CLA. Mice receiving the 0.2% and 0.6% dose of 10,12 CLA plus linoleic acid or the CLA isomer mixture had decreased white adipose tissue (WAT) and brown adipose tissue (BAT) mass and increased incorporation of CLA isomers in epididymal WAT and liver. Notably, in mice receiving 0.2% of both CLA treatments, the mRNA levels of genes associated with browning, including uncoupling protein 1 (UCP1), UCP1 protein levels, and cytochrome c oxidase activity, were increased in epididymal WAT. CLA-induced browning in WAT was accompanied by increases in mRNA levels of markers of inflammation. Muscle cytochrome c oxidase activity and BAT UCP1 protein levels were not affected by CLA treatment. These data suggest a linkage between decreased adiposity, browning in WAT, and low-grade inflammation due to consumption of 10,12 CLA.

Modulation of oxidative stress by γ-glutamylcysteine (GGC) and conjugated linoleic acid (CLA) isomer mixture in human umbilical vein endothelial cells

Individually, γ-glutamylcysteine (GGC), a dipeptide and precursor of glutathione (GSH), and conjugated linoleic acid (CLA), a trans-fatty acid, exhibit antioxidant properties. The objective of this study was to compare effects of co-administration of GGC and CLA to treatment with GGC alone on oxidative stress and GSH synthesis in human endothelial cells. Changes in levels of 8-epi-PGF2α, thiobarbituric acid reactive substances (TBARS), GSH, total antioxidants, GSH synthetase (GSS) expression, and transcription factor DNA binding were assessed in human umbilical vein endothelial cells (HUVEC) treated with GGC alone (100μmol/L) or combined with CLA isomer mixture (10, 50, 100μmol/L) for 24h. Significantly higher levels of TBARS, 8-epi-PGF2α, GSH, and GSS protein were found in cells treated with GGC and 10μmol/L CLA, compared to cells treated with GGC alone, indicative of prooxidant effects of CLA. Approximately 40% cell death was microscopically observed in cells incubated with GGC and 100μmol/L CLA. Despite lower levels of GSH, treatment with GGC and 50μmol/L CLA appeared to be protective from oxidative stress similar to treatment with GGC alone, as indicated by lower levels of TBARS, compared to control cells not treated with GGC and CLA.

Moderate doses of conjugated linoleic acid isomers mix contribute to lowering body fat content maintaining insulin sensitivity and a noninflammatory pattern in adipose tissue in mice

Conjugated linoleic acid (CLA) modulates body composition, especially by reducing adipose tissue. However, despite the increasing knowledge about CLA's beneficial effects on obesity management, the mechanism of action is not yet fully understood. Furthermore, in some human studies fat loss is accompanied by impairment in insulin sensitivity, especially when using the trans-10, cis-12 isomer. The aim of this work was to study the effects of moderate doses of CLA on body fat deposition, cytokine profile and inflammatory markers in mice. Mice were orally treated with a mixture of CLA isomers, cis-9, trans-11 and trans-10, cis-12 (50:50), for 35 days with doses of CLA1 (0.15 g CLA/kg body weight) and CLA2 (0.5 g CLA/kg body weight). CLA had discrete effects on body weight but caused a clear reduction in fat mass (retroperitoneal and mesenteric as the most sensitive depots), although no other tissue weights were affected. Glucose and insulin were not altered by CLA treatment, and maintenance of glucose homeostasis was observed even under insulin overload. The study of gene expression (Emr1, MCP-1, IL-6, TNFα, PPARγ2 and iNOS) either in adipocytes and/or in the stromal vascular fraction indicated that CLA does not lead to the infiltration of macrophages in adipose tissue or to the induction of expression of pro-inflammatory cytokines. The use of a mixture of both isomers, as well as moderate doses of CLA, is able to induce a reduction of fat gain without an impairment of adipose tissue function while preserving insulin sensitivity.

Dietary trans-10, cis-12 Conjugated Linoleic Acid Reduces Early Glomerular Enlargement and Elevated Renal Cyclooxygenase-2 Levels in Young Obese fa/fa Zucker Rats

Conjugated linoleic acid (CLA) slows the progression of disease in models of chronic kidney disease. Because obesity is associated with nephropathy and increased renal cyclooxygenase (COX) levels, the effects of dietary CLA on kidney function, morphology, and COX protein levels in the kidneys of young obese (fa/fa) Zucker rats, a model of metabolic syndrome, were examined. In study 1, 6-wk-old fa/fa and lean Zucker rats were given a mixture of CLA isomers (1.5% CLA, wt:wt) or the control diet (CTL) with no CLA for 8 wk. To examine specific isomer effects, study 2 used the same model with the following diets: 0.4% (g/g) cis-9, trans-11 (c9,t11) CLA; 0.4% trans-10, cis-12 (t10,c12) CLA; a combination of these 2 isomers (0.4% each); or CTL diets with no CLA. In study 1, fa/fa rats given the CLA mixture had 11% smaller kidney weights and 28% smaller glomeruli, and feed intake and body weight did not differ from the CTL rats. In study 2, diet also did not affect body weights, but fa/fa rats given a diet containing t10,c12 CLA had 7% lower kidney weights, 20% smaller glomeruli, and 39% lower COX-2 protein levels than CTL rats. In conclusion, dietary t10,c12 CLA reduces the enlargement of glomeruli in young obesity-associated nephropathy and is associated with lower protein levels of renal COX-2. Long-term studies with CLA supplementation are required to determine whether these changes would lead to reduction in development of renal disease associated with obesity.

Conjugated Linoleic Acid (CLA) Inhibits Expression of the Spot 14 (THRSP) and Fatty Acid Synthase Genes and Impairs the Growth of Human Breast Cancer and Liposarcoma Cells

Spot 14 (THRSP, S14) is a nuclear protein involved in the regulation of genes required for fatty acid synthesis in normal and malignant mammary epithelial and adipose cells. Harvatine and Bauman (1) reported that conjugated linoleic acid (CLA) inhibits S14 gene expression in bovine mammary and mouse adipose tissues and reduces milk fat production in cows. We hypothesized that CLA inhibits S14 gene expression in human breast cancer and liposarcoma cells and that this will retard their growth. Exposure of T47D breast cancer cells to a mixture of CLA isomers reduced the expression of the S14 and fatty acid synthase (FAS) genes. The mixture caused a dose-related inhibition of T47D cell growth, as did pure c9, t11 and t10, c12-CLA, but not linoleic acid. Similar effects were observed in MDA-MB-231 breast cancer cells. Provision of 8 μM palmitate fully (CLA mix, t10, c12-CLA) or partially (c9, t11-CLA) reversed the antiproliferative effect in T47D cells. CLA likewise suppressed levels of S14 and FAS mRNAs in liposarcoma cells and caused growth inhibition that was prevented by palmitic acid. CLA did not affect the growth of nonlipogenic HeLa cells or human fibroblasts. We conclude that as in bovine mammary and mouse adipose cells, CLA suppresses S14 and FAS gene expression in human breast cancer and liposarcoma cells. Rescue from the antiproliferative effect of CLA by palmitic acid indicates that reduced tumor lipogenesis is a major mechanism for the anticancer effects of CLA

Dietary Conjugated Linoleic Acid Renal Benefits and Possible Toxicity vary with Isomer, Dose and Gender in Rat Polycystic Kidney Disease

Conjugated linoleic acid (CLA) is anti-proliferative and anti-inflammatory in the Han:SPRD-cy rat model of kidney disease. We used different doses of CLA and examined effects on renal histological benefit, the renal PPARgamma system and hepatic and renal levels of CLA isomers. Male and female offspring of Han:SPRD-cy heterozygotes were fed diets with 0, 1 or 2% CLA isomer mixture for 12 weeks before dual-energy X-ray absorptiometry, harvest of renal and hepatic tissue for histologic and lipid analysis. Both CLA diets reduced body fat content in both genders but did not change lean body mass. CLA produced a dose dependent reduction in female renal cystic change. CLA reduced fibrosis, but this reduction was significantly less with higher dose in males. CLA reduced macrophage infiltration, tissue oxidized LDL content and proliferation of epithelial cells. Serum creatinine rose significantly in female animals fed CLA diets. CLA treatment did not change PPARgamma activation. A significant negative correlation with renal content of the 18:2 c9,t11 isomer and the sum of histologic effects was identified. CLA reduces histologic renal injury in the Han:SPRD-cy rat model probably inversely proportionate to c9,t11 renal content. Possible functional CLA toxicity at high dose in female animals warrants further exploration.

A Diet Rich in Conjugated Linoleic Acid and Butter Increases Lipid Peroxidation but Does Not Affect Atherosclerotic, Inflammatory, or Diabetic Risk Markers in Healthy Young Men

Intake of conjugated linoleic acid (CLA) has been demonstrated to beneficially affect risk markers of atherosclerosis and diabetes in rats. CLA is naturally found in milk fat, especially from cows fed a diet high in oleic acid, and increased CLA intake can occur concomitantly with increased milk fat intake. Our objective was to investigate the effect of CLA as part of a diet rich in butter as a source of milk fat on risk markers of atherosclerosis, inflammation, diabetes type II, and lipid peroxidation. A total of 38 healthy young men were given a diet with 115 g/d of CLA-rich fat (5.5 g/d CLA oil, a mixture of 39.4% cis9, trans11 and 38.5% trans10, cis12) or of control fat with a low content of CLA in a 5-wk double-blind, randomized, parallel intervention study. We collected blood and urine before and after the intervention. The fatty acid composition of plasma triacylglycerol, cholesterol esters, and phospholipids reflected that of the intervention diets. The CLA diet resulted in increased lipid peroxidation measured as an 83% higher 8-iso-prostaglandin F2α concentration compared with the control, P < 0.0001. We observed no other significant differences in the effect of the interventions diets. In conclusion, when given as part of a diet rich in butter, a mixture of CLA isomers increased lipid peroxidation but did not affect risk markers of cardiovascular disease, inflammation, or fasting insulin and glucose concentrations.

Fatty acid and conjugated linoleic acid isomer profiles in human milk fat

AbstractThe fatty acid composition of 39 mature human milk samples from four Spanish women collected between 2 and 18 weeks during lactation was studied by gas chromatography. The conjugated linoleic acid (CLA) isomer profile was also determined by silver‐ion HPLC (Ag+‐HPLC) with three columns in series. The major fatty acid fraction in milk lipids throughout lactation was represented by the monounsaturated fatty acids, with oleic acid being the predominant compound (36–49% of total fatty acids). The saturated fatty acid fraction represented more than 35% of the total fatty acids, and polyunsaturated fatty acids ranged on average between 10 and 13%. Mean values of total CLA varied from 0.12 to 0.15% of total fatty acids. The complex mixture of CLA isomers was separated by Ag+‐HPLC. Rumenic acid (RA, cis‐9 trans‐11 C18:2) was the major isomer, representing more than 60% of total CLA. Trans‐9 trans‐11 and 7‐9 (cis‐trans + trans‐cis) C18:2 were the main CLA isomers after RA. Very small amounts of 8‐10 and 10‐12 C18:2 (cis‐trans + trans‐cis) isomers were detected, as were different proportions of cis‐11 trans‐13 and trans‐11 cis‐13 C18:2. Although most of the isomers were present in all samples, their concentrations varied considerably.

Effect of dietary conjugated linoleic acid and selenized yeast on the concentration of fatty acids and minerals in rats

The main objective of this study was to evaluate the influence of diets enriched in individual conjugated linoleic acid (CLA) isomers, their mixture, and/or selenized yeast (Se-yeast) on the concentration of CLA isomers, long-chain polyunsaturated fatty acids (PUFA) and Se in the heart, muscles and liver of rats. The investigation was performed on 73 female Wistar rats (8 weeks of age, 200 g initial BW). After one week sub-maintenance feeding, rats received diets supplemented with 1% individual CLA isomers or 1 or 2% of a CLA isomers mixture, without or with 1.2 mg Se/kg (as Se-yeast) for 29 days. Feeding diets with 2% CLA isomer mixture reduced feed intake and body weight gain of rats, while addition of trans10,cis12 CLA and Se-yeast resulted in the highest body weight gain. CLA supplementation generally elevated the concentration of CLA isomers in heart and muscles significantly, although cis9,trans11 CLA accumulated preferentially. Regardless of the presence of Se-yeast, the dietary enrichment with CLA isomers caused a reduction in the capacity of Δ9-desaturase. Addition of Se-yeast to diets with individual CLA isomers or a 1% mixture of CLA isomers elevated the accumulation of CLA isomers in the heart and muscles, whereas all treatments with supplemented CLA and Se-yeast increased the accumulation of Se in rats compared with animals fed the diet containing Se only. Furthermore, CLA isomer supplementation decreased the concentration of PUFA and total fatty acids in the heart and muscles compared with control rats. Moreover, addition of CLA isomers interfered in the conversion of linoleic and linolenic acids to higher metabolites due to competition of CLA isomers for the same enzymes (Δ6-, Δ5-, Δ4-desaturases and elongase).

The influence of dietary conjugated linoleic acid isomers and selenized yeast on the fatty acid profile of the spleen, pancreas and kidneys of rats

The influence of 1.2 ppm dietary selenium added in the form of selenized yeast (Se-yeast) and of a mixture of conjugated linoleic acid (CLA) isomers added to a level of 1 or 2%, of cis9trans11CLA (c9t11) added to 1%, and of trans10cis12CLA (t10c12) added to 1% on the body and organ gains of rats and on the concentration of CLA isomers and other fatty acids in the spleen, pancreas and kidneys was investigated. Total fatty acids in the studied organs were separated as methyl esters using long-capillary gas-liquid chromatography with flame-ionization detection, while nonmethylated fatty acids containing conjugated double bonds were examined using silver-ion liquid chromatography with fotodiode detection. Free fatty acids were obtained by mild saponification, whereas their methyl esters, by base- and acid-catalyzed methylation. Feeding t10c12 and Se-yeast resulted in the highest increase in rat growth and organ gain. All diets enriched in CLA isomer(s) significantly elevated the concentration of CLA isomers in the organs; the highest concentration of CLA isomers was found in the pancreas, the smallest, in the spleen. The addition of Se to diets containing CLA isomer(s) usually showed a statistical tendency or increase in the concentration of CLA isomers in the organs. Our results demonstrate that t10c12 was metabolized faster than c9t11 in the pancreas and kidneys, whereas the addition of Se-yeast to the diets with CLA isomer(s) reduced the rate of t10c12 metabolism. A 2% dietary content of a mixture of CLA isomers or of t10c12 usually tended to increase or significantly increased the concentration of linoleic, linolenic, and arachidonic acids and of n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) in the organs. Dietary c9t11 and a 1% content of the mixture of CLA isomers weakly influenced the concentrations of these fatty acids in the organs, whereas the diet enriched simultaneously in c9t11 and Se-yeast resulted in a statistical tendency or increase in the concentration of long-chain n-3 PUFA and the

The influence of dietary conjugated linoleic acid isomers and Se on the fatty acid profile in rat blood plasma and selected tissues

The Kielanowski Institute of Animal Physiology and Nutrition,Polish Academy of Sciences05-110 Jablonna, Poland(Received 14 March 2006; accepted 5 July 2006)ABSTRACT The objective of this study was to determine the conjugated linoleic acid (CLA) isomer composition of blood plasma and other organ tissues of Wistar rats fed a diet enriched with 1 or 2% CLA isomer(s) and 2 ppm Se as sodium selenate for 4 weeks. The dietary supplement of CLA isomers significantly elevated the concentration of CLA isomers and other fatty acids containing conjugated double bonds in plasma, spleen, pancreas, heart, and kidney tissues. cis9,trans11CLA was preferentially accumulated in plasma and organ tissues of rats fed the CLA isomer mixture with or without Se, while the percentage contribution of trans10,cis12CLA in the tissues of organs tended to be lower than its percentage in the administered CLA isomer mixture. Dietary CLA isomer(s) increased the Ca content of whole blood, while the diet with the CLA isomer(s) and Se increased the concentration of Mg and Se in spleen tissue. The experimental diets did not produce any substantial changes in the Fe or Zn concentrations in blood or spleen tissue. The diet enriched in trans10,cis12CLA and Se significantly increased spleen, pancreas and heart weights. Regardless of the presence of Se, the diet enriched in CLA isomer(s) stimulated the accumulation of polyunsaturated fatty acids in blood plasma, and in pancreas, heart, and kidney tissues. The diets enriched in the CLA isomer(s) usually resulted in a decrease of the monounsaturated fatty acid concentration and Δ9-desaturase capacity in plasma, spleen, pancreas, and kidney tissues, but not in noticeably decreased concentrations in heart and brain tissues. The presence of both Se and the CLA isomer(s) produced less consistent changes in the capacity of Δ9 desaturase and monounsaturated fatty acid concentrations compared with the effect of the diet with the CLA isomer(s) only. KEY WORDS: CLA isomers, fatty acids, Se, Zn, Fe, Ca, Mg, blood plasma, rat tissue

Lack of effect of dietary conjugated linoleic acids naturally incorporated into butter on the lipid profile and body composition of overweight and obese men

Dietary conjugated linoleic acid (CLA) is known to reduce atherosclerosis, plasma total and LDL-cholesterol concentrations, and body fat accumulation in several animal species. Of the few studies that investigated the effects of CLA supplementation in humans, all used commercially formulated oral supplements made from a mixture of CLA isomers. We compared the effects on plasma lipoproteins and body composition of the consumption of a modified butter naturally enriched with CLA (CLA-B: 4.22 g CLA/100 g butter fat) by the addition of sunflower oil to the diet of dairy cows with the consumption of a control butter (CON-B) that was low in CLA (0.38 g CLA/100 g butter fat). In a crossover design study including an 8-wk washout period, 16 men [x +/- SD age: 36.6 +/- 12.4 y; body mass index (in kg/m2): 31.2 +/- 4.4] were fed each of the 2 experimental isoenergetic diets, providing 15% of energy as protein, 45% as carbohydrates, and 40% as lipids, of which >60% was derived from experimental fats, for 4 wk. Consumption of the CLA-B diet induced a significantly (P < 0.05) smaller reduction in plasma total cholesterol and in the ratio of total to HDL cholesterol (-0.02 mmol/L and -0.00, respectively) than did consumption of the CON-B diet (-0.26 mmol/L and-0.34, respectively). Abdominal adipose tissue area measured by computed tomography showed no difference in accumulation of either visceral or subcutaneous adipose tissue after the 2 experimental diets. These results suggest that a 10-fold CLA enrichment of butter fat does not induce beneficial metabolic effects in overweight or obese men.

Congulated linoleic acid decreases cellular proliferation and inhibits nuclear factor– κB and activator protein 1 activation in PC3 cancerous prostate epithelial cells

The precise etiologic factors that initiate and enhance the progression of prostate cancer remains unknown, but diet and lifestyle factors have come forth as significant contributing factors. Conjugated linoleic acid (CLA) is a family of fatty acid isomers found in ruminant food products that appear to have chemopreventive properties in animal models of cancer and antiproliferative effects in several types of cancer cells. Dysregulation and constitutive activation of nuclear factor– κB (NF κB) and activator protein 1 (AP1) is found in malignant prostate cells, and dietary components that target these transcription factors may prove to be effective chemopreventive agents. The purpose of this study was to examine the antiproliferative effects of CLA on PC3 cancerous prostate epithelial cells and test the ability of CLA to modulate transcription factors NF κB and AP1. We found that a mixture of CLA isomers potently inhibited cellular proliferation of androgen-independent PC3 prostate carcinoma cells in a dose-dependent manner. Electromobility shift assays also revealed that CLA inhibited constitutive activation of NF κB and AP1 transcription factors in PC3 cells. Mobility shift assays demonstrated that CLA also induced activation peroxisome proliferator–activated receptors (PPARs). However, time course studies revealed that PPAR activation occurred after inhibitory effects on NF κB and AP1, suggesting that inhibition of NF κB and AP1 did not depend on PPAR activation. The ability of CLA to attenuate inflammatory processes and cellular proliferation by the inhibition of these transcription factors could be the key in their ability to limit cancer development.

Conjugated linoleic acid suppresses the secretion of atherogenic lipoproteins from human HepG2 liver cells

Studies in healthy humans have shown that consumption of conjugated linoleic acid (CLA) significantly reduced very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) blood concentrations. We propose that decreased concentrations are due to the inhibition of VLDL production and secretion [measured by apolipoprotein B100 (apoB100)] from the liver. To investigate the effects of a mixture of CLA isomers on VLDL metabolism, HepG2 liver cells were incubated for 24 h with 50 micromol/L of the different fatty acids. Effects of CLA were compared to a saturated fatty acid (palmitic acid), an n-6 fatty acid (linoleic acid) and no treatment (control). HepG2-cell apoB100 levels were measured using Western blotting. ApoB100 secretion was significantly decreased in cells treated with CLA (44%, p<0.005) compared to control cells and those enriched with palmitic acid. Treatment of cells with CLA also decreased intracellular cholesterol levels. Collectively, these results demonstrate that CLA reduces apoB100 production and secretion compared to saturated and polyunsaturated fatty acids, possibly by limiting the availability of free cholesterol (required for apoB100 production). A reduction in apoB100 production in the body would decrease the levels of VLDL and atherogenic LDL and thus reduce the risk of developing cardiovascular disease.

Influence of dietary conjugated linoleic Acid and fat source on body fat and apoptosis in mice.

To determine whether altered dietary essential fatty acid (linoleic and arachidonic acid) concentrations alter sensitivity to conjugated linoleic acid (CLA)-induced body fat loss or DNA fragmentation. Mice were fed diets containing soy oil (control), coconut oil [essential fatty acid deficient (EFAD)], or fish oil (FO) for 42 days, and then diets were supplemented with a mixture of CLA isomers (0.5% of the diet) for 14 days. Body fat index, fat pad and liver weights, DNA fragmentation in adipose tissue, and fatty acid profiles of adipose tissue were determined. The EFAD diet decreased (p < 0.05) linoleic and arachidonic acid in mouse adipose tissue but did not affect body fat. Dietary CLA caused a reduction (p < 0.05) in body fat. Mice fed the EFAD diet and then supplemented with CLA exhibited a greater reduction (p < 0.001) in body fat (20.21% vs. 6.94% in EFAD and EFAD + CLA-fed mice, respectively) compared with mice fed soy oil. Dietary FO decreased linoleic acid and increased arachidonic acid in mouse adipose tissue. Mice fed FO or CLA were leaner (p < 0.05) than control mice. FO + CLA-fed mice did not differ in body fat compared with FO-fed mice. Adipose tissue apoptosis was increased (p < 0.001) in CLA-supplemented mice and was not affected by fat source. Reductions in linoleic acid concentration made mice more sensitive to CLA-induced body fat loss only when arachidonic acid concentrations were also reduced. Dietary essential fatty acids did not affect CLA-induced DNA fragmentation.

Conjugated linoleic acid (CLA) content and fatty acids composition of muscle in rats fed isomers of CLA and selenium

The aim of the study was to determine the influence of conjugated isomers of linoleic acid (CLA) and/or selenium (Se) on the body mass gain of rats, feed intake, and the levels of CLA isomers and some other fatty acids in the femoral muscle. Rat diets enriched in Se, the trans-10,cis-12 isomer and mixtures of the CLA isomers (regardless Se supplementation) tended to decrease body mass gain compared with control rats, while simultaneously supplementation with Se and the trans-10,cis-12 isomer resulted in the highest increase. A mixture of CLA isomers and/or Se supplementation, and the trans-10,cis-12 isomer decreased feed intake, whereas the cis-9,trans-11 isomer, regardless of Se supplementation, only slightly influence of feed intake. Enriching diets with CLA isomers increased their level in muscles as well as the level of non-CLA isomers containing conjugated double bonds (CD). In rats receiving simultaneously Se and mixtures of the CLA isomers or individual CLA isomers the CLA isomers and CD levels in muscles were higher compared with rats fed only the CLA isomers. Rats fed individual isomers or their mixture showed minute changes in C8:0 and C10:0 concentrations in muscles, while the C12:0, C14:0, C16:0 and C18:0 contents were generally lower. A small increase in C10:0 and C16:0 content was found in rats fed the trans-10,cis-12 isomer. Supplementing Se to diets enriched in CLA isomers usually resulted in an increase in the saturated fatty acid content in muscles in comparison with rats fed only CLA isomers. The linoleic acid content in muscles was enhanced by the Se supplemented diets enriched in the trans-10,cis-12 isomer or in the 2% CLA isomer mixture, although 1% mixture of the CLA isomers or the cis-9,trans-11 isomer dosed simultaneously with Se also increased the level of linoleic acid, albeit insignificantly. The Se supplemented diet enriched 184 CLA IN MUSCLES OF RATS FED CLA ISOMERS AND SE 185 CZAUDERNA M. ET AL. in the trans-10,cis-12 isomer or 2% mixture of the CLA isomers produced the highest increase of γ-linolenic acid, the total fatty acid and polyunsaturated fatty acid content in rat muscle.

Trans-10, cis-12 conjugated linoleic acid reduces insulin-like growth factor-II secretion in HT-29 human colon cancer cells.

We previously demonstrated that a mixture of conjugated linoleic acid (CLA) isomers decreases colon cancer incidence in rats treated with 1,2-dimethylhydrazine. Our in vitro studies have also shown that CLA inhibits the growth of HT-29 cells, a human colon cancer cell line. When we compared the individual potencies of the two main isomers found in the mixture of CLA isomers (e.g., cis-9, trans-11 [c9t11] and trans-10, cis-12 [t10c12]), t10c12 CLA decreased viable cell numbers in a dose-dependent manner. By contrast, c9t11 CLA had no effect. Therefore, the present study examined whether the decreased cell growth is related to changes in secretion of insulin-like growth factor (IGF)-II and/or IGF-binding proteins (IGFBPs) that have been shown to regulate HT-29 cell proliferation. Cells were incubated in serum-free medium with various concentrations of the individual CLA isomers, and immunoblot analysis of 24-hour, serum-free, conditioned media using a monoclonal anti-IGF-II antibody was performed. HT-29 cells secreted both mature 7,500 apparent molecular weight (M(r)) and higher-M(r) forms of IGF-II. t10c12 CLA decreased the levels of the higher-M(r) and the mature form of IGF-II in a dose-dependent manner, whereas c9t11 CLA had no effect. Ligand blot analysis of conditioned medium using (125)I-IGF-II revealed that the production of IGFBP-2 and IGFBP-4 was also decreased by t10c12 CLA, whereas c9t11 CLA had no effect. Exogenous IGF-II abrogated the growth inhibition induced by t10c12 CLA. These results indicate that inhibition of HT-29 cell growth by t10c12 CLA may be mediated by decreasing IGF-II secretion in these cells.

Conjugated Linoleic Acid in Humans: Regulation of Adiposity and Insulin Sensitivity

Conjugated linoleic acid (CLA) isomers, a group of positional and geometric isomers of linoleic acid [18:2(n-6)], have been studied extensively due to their ability to modulate cancer, atherosclerosis, obesity, immune function and diabetes in a variety of experimental models. The purpose of this review was to examine CLA's isomer-specific regulation of adiposity and insulin sensitivity in humans and in cultures of human adipocytes. It has been clearly demonstrated that specific CLA isomers or a crude mixture of CLA isomers prevent the development of obesity in certain rodent and pig models. This has been attributed mainly to trans-10, cis-12 CLA, both in vivo and in vitro. However, CLA's ability to modulate human obesity remains controversial because data from clinical trials using mixed isomers are conflicting. In support of some studies in humans, our group demonstrated that trans-10, cis-12 CLA prevents triglyceride (TG) accumulation in primary cultures of differentiating human preadipocytes. In contrast, cis-9, trans-11 CLA increases TG content. Closer examination has revealed that CLA's antiadipogenic actions are due, at least in part, to regulation of glucose and fatty acid uptake and metabolism. This review presents our current understanding of potential isomer-specific mechanisms by which CLA reduces human adiposity and insulin sensitivity.