The trans-10,cis-12 isomer of conjugated linoleic acid reduces hepatic triacylglycerol content without affecting lipogenic enzymes in hamsters

Conjugated linoleic acid (CLA) refers to the positional and geometric dienoic isomers of linoleic acid. The dietary intake of CLA has been associated with changes in lipid metabolism. The aim of the present work was to assess the effects of the two main isomers of CLA on sterol regulatory element binding protein (SREBP)-1a and SREBP-1c mRNA levels, as well as on mRNA levels and the activities of several lipogenic enzymes in liver. For this purpose hamsters were fed an atherogenic diet supplemented with 5 g linoleic acid, cis-9,trans-11 or trans-10,cis-12 CLA/kg diet for 6 weeks. The trans-10,cis-12 isomer intake produced significantly greater liver weight, but also significantly decreased liver fat accumulation. No changes in mRNA levels of SREBP-1a, SREBP-1c and lipogenic enzymes, or in the activities of these enzymes, were observed. There was no effect of feeding cis-9,trans-11 CLA. These results suggest that increased fat accumulation in liver does not occur on the basis of liver enlargement produced by feeding the trans-10,cis-12 isomer of CLA in hamsters. The reduction in hepatic triacylglycerol content induced by this isomer was not attributable to changes in lipogenesis.     

Adipose depletion and apoptosis induced by trans-10, cis-12 conjugated linoleic Acid in mice

OBJECTIVE: To compare the effectiveness of a conjugated linoleic acid (CLA) isomer mixture (mCLA) with each main isomer [trans-10,cis-12 CLA (CLA10,12) and cis-9,trans-11 CLA (CLA9,11)] in causing body lipid loss and adipose tissue apoptosis. RESEARCH METHODS AND PROCEDURES: Mice selected over 16 generations for high (MH) or low (ML) energy expenditure and a control group (MC) were fed diets containing either soy oil or soy oil plus mCLA, CLA10,12, or CLA9,11 for 5 days in one study and 14 days in a second study. RESULTS: Mice fed mCLA or CLA10,12 had less body lipid (p < 0.05), smaller retroperitoneal fat pads (p < 0.05), and ate less (p < 0.01) than mice fed no CLA or CLA9,11 for 5 days. Mice consuming 1% mCLA or 0.5% CLA10,12 gained less weight (p < 0.01) and had less body lipid (p < 0.05) and smaller epididymal (p < 0.05) and retroperitoneal fat pads (p < 0.01) than mice consuming either control or 0.5% CLA9,11-containing diets for 14 days. Only mCLA and CLA10,12 increased apoptosis in retroperitoneal fat pads (p < 0.01). The effects of mCLA and CLA10,12 were independent of genetic line except for the effect on adipocyte apoptosis. Mice of the MH line were slightly less sensitive than MC or ML mice to CLA-induced adipose tissue apoptosis. DISCUSSION: CLA10,12, but not CLA9,11, can induce both body fat loss and adipose apoptosis. Although mice of a genotype with less body fat and greater metabolic rate and feed intake appear less sensitive, these CLA effects are robust for mice of varying metabolic background.     

Dietary trans-10, cis-12 and cis-9,trans-11 conjugated linoleic acids induce apoptosis in the colonic mucosa of rats treated with 1,2-dimethylhydrazine

We have previously shown that a diet containing a mixture of conjugated linoleic acid (CLA) isomers reduces the incidence of colon tumors in rats treated with 1,2-dimethylhydrazine (DMH). The present study examined which of the two main CLA isomers, trans-10,cis-12 CLA (t10c12) or cis-9,trans-11 CLA (c9t11), decreases colon tumor numbers and the mechanisms for this effect. Six-week-old, male Sprague-Dawley rats were intramuscularly injected with 15 mg/kg of DMH twice per week for 6 weeks and fed a control diet, 1% t10c12, or 1% c9t11 for 30 weeks. The experimental diets were initiated simultaneously with DMH injection. The tumor numbers were decreased and the apoptotic index was significantly increased in the colonic mucosa of the t10c12 and c9t11 groups, when the results were compared with those of the control group. The protein levels of Bcl-2 and cyclooxygenase-2 were significantly decreased, but Bax levels were increased in both of the CLA isomer groups. The thromboxane B(2) levels in colonic mucosa were substantially lower in the two CLA isomer groups than in the control group. However, there was no difference in these parameters between the CLA isomer groups. We have demonstrated that diets containing 1% t10c12 and c9t11 were equally effective in reducing tumor numbers and inducing apoptosis in the colonic mucosa of rats treated with DMH. These results indicate that Bcl-2 family protein levels are associated with CLA-induced apoptosis in the colonic mucosa of DMH-treated rats.     

Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans

BACKGROUND: Conjugated linoleic acid (CLA) is reported to have weight-reducing and antiatherogenic properties when fed to laboratory animals. However, the effects of CLA on human health and, in particular, the effects of individual CLA isomers are unclear. OBJECTIVE: This study investigated the effects of 3 doses of highly enriched cis-9,trans-11 (0.59, 1.19, and 2.38 g/d) or trans-10,cis-12 (0.63, 1.26, and 2.52 g/d) CLA preparations on body composition, blood lipid profile, and markers of insulin resistance in healthy men. DESIGN: Healthy men consumed 1, 2, and 4 capsules sequentially, containing either 80% cis-9,trans-11 CLA or 80% trans-10,cis-12 CLA for consecutive 8-wk periods. This phase was followed by a 6-wk washout and a crossover to the other isomer. RESULTS: Body composition was not significantly affected by either isomer of CLA. Mean plasma triacylglycerol concentration was higher during supplementation with trans-10,cis-12 CLA than during that with cis-9,trans-11 CLA, although there was no influence of dose. There were significant effects of both isomer and dose on plasma total cholesterol and LDL-cholesterol concentrations but not on HDL-cholesterol concentration. The ratios of LDL to HDL cholesterol and of total to HDL cholesterol were higher during supplementation with trans-10,cis-12 CLA than during that with cis-9,trans-11 CLA. CLA supplementation had no significant effect on plasma insulin concentration, homeostasis model for insulin resistance, or revised quantitative insulin sensitivity check index. CONCLUSION: Divergent effects of cis-9,trans-11 CLA and trans-10,cis-12 CLA appear on the blood lipid profile in healthy humans: trans-10,cis-12 CLA increases LDL:HDL cholesterol and total:HDL cholesterol, whereas cis-9,trans-11 CLA decreases them.     

Dietary conjugated linoleic acid differentially alters fatty acid composition and increases conjugated linoleic acid content in porcine adipose tissue

Conjugated linoleic acids (CLA) have been shown to decrease body fat content in pigs. It is possible that feeding pigs diets rich in CLA may increase carcass lipid CLA to levels that could provide health benefits when included as a part of a healthy diet. Therefore, the aim of the present study was to determine whether dietary CLA supplementation has any effect on the fatty acid composition of subcutaneous and intramuscular adipose tissue in pigs. Thirty-five female cross bred (Large White x Landrace) pigs (initial weight 57.2 kg and initial P2 back fat 11.5 mm) were used in the present study. Pigs were housed individually and randomly allocated to one of six dietary treatments (0.00, 1.25, 2.50, 5.00, 7.50 and 10.00 g CLA55 (55 g CLA isomers/100 g total fatty acids; Natural Lipids Ltd, Hovdebygda, Norway)/kg) and fed their respective diets for 8 weeks. Twelve CLA isomers in the diet and in pig tissue lipids were separated by Ag+-HPLC. CLA was incorporated at fivefold higher levels in subcutaneous fat as compared with intramuscular fat and in a dose-dependant manner. Overall, the transfer efficiency of CLA was maximized at 5.00 g CLA55/kg. However, there was clear selectivity in the uptake or incorporation of cis,trans-9,11 isomer over the trans,cis-10,12 isomer. In general, CLA supplementation produced significant changes in skeletal muscle and adipose tissue fatty acid composition, indicating that dietary CLA had a potent affect on lipid transport and metabolism in vivo. Significant increases in myristic, palmitic and palmitoleic acids and a reduction in arachidonic acid were observed, suggesting an alteration in activity of delta5-, delta6- and delta9-desaturases in pig adipose tissue. In conclusion, feeding pigs diets supplemented with CLA increases carcass lipid CLA, but also results in changes in the fatty acid profile in pig fat that could potentially outweigh the benefits of CLA.     

Conjugated linoleic acid differentially modifies fatty acid composition in subcellular fractions of muscle and adipose tissue but not adiposity of postweaning pigs

This study examined the interaction between conjugated linoleic acid (CLA) and dietary fat type on the enrichment of subcellular fractions, the Delta(9) desaturase index and adiposity in pigs. Early weaned piglets (n = 6/group) were fed for 35 d diets supplemented with 15 g/100 g diet beef tallow or corn oil, or 12 g/100 g tallow or corn oil plus 3 g CLA. There were no effects of dietary fat or CLA on the mass of dissected skin, bone, muscle or adipose tissue of the 7th to 9th thoracic rib sections. Medial subcutaneous adipose tissue of pigs fed tallow had smaller adipocytes than that of pigs fed corn oil. The lateral subcutaneous site was unaffected by dietary fat type. Microsomes accumulated <50% the concentration of trans-10,cis-12, cis-11,trans-13, and cis-9,trans-11 CLA as membrane and nonmembrane fractions of adipose tissue and longissimus muscle. There was no evidence of preferential incorporation of any CLA isomer into any of the subcellular fractions. Addition of CLA to the diets reduced adipose tissue nonmembrane monounsaturated fatty acids (MUFA; g/100 g total fatty acids) by 15% in corn oil-fed pigs and by 19% in tallow-fed pigs. Total saturated fatty acids (SFA) were increased by CLA commensurately in this lipid fraction. This resulted in a reduced Delta(9) desaturase index [MUFA/(SFA + MUFA)] in the nonmembrane lipid fraction of pigs fed either the corn oil or tallow diets. Thus, in spite of marked effects on fatty acid composition and the Delta(9) desaturase index, CLA had no effect on adiposity in early weaned piglets fed high fat diets.     

Trans-10, cis-12, but not cis-9, trans-11, conjugated linoleic acid attenuates lipogenesis in primary cultures of stromal vascular cells from human adipose tissue

We have previously shown that both a commercially available mixture of conjugated linoleic acid (CLA) isomers and the trans-10, cis-12 isomer of CLA reduced the triglyceride (TG) content and induced apoptosis in differentiating cultures of murine 3T3-L1 preadipocytes. However, the influence of CLA isomers on differentiating human (pre)adipocytes is unknown. Therefore, we conducted a series of studies using primary cultures of stromal vascular cells isolated from human adipose tissue to determine: 1) the influence of seeding density and thiazolidinedione (TZD) concentration on TG content; 2) the chronic dose response of cis-9, trans-11 CLA vs. trans-10, cis-12 CLA on TG content; 3) whether chronic linoleic acid supplementation could rescue the TG content of CLA-treated cultures; and 4) whether trans-10, cis-12-mediated reduction in cellular TG was due to decreased lipogenesis and/or increased lipolysis. In expt. 1, the TG content [micromol/(L x 10(6) cells)] increased as both seeding density and TZD concentration increased. For example, cultures seeded at 4 x 10(4) cells/cm(2) and supplemented with 10 micromol/L BRL 49653 had 10-fold more TG than similarly seeded cultures without BRL 49653. In expt. 2, TG content decreased as the level of trans-10, cis-12 CLA increased from 1 to 10 micromol/L, whereas the TG content increased with increasing concentrations of either linoleic acid or cis-9, trans-11 CLA. In expt. 3, linoleic acid supplementation restored the TG content of cultures treated with trans-10, cis-12 CLA compared with cultures treated with CLA alone, suggesting that attenuation of TG content by CLA is reversible. In expt. 4, glucose incorporation into total lipid decreased with increasing levels of trans-10, cis-12 CLA, whereas neither CLA isomer acutely affected lipolysis. These data suggest that the reported antiobesity actions of a supplement containing a crude mixture of CLA isomers given to humans may be due to inhibition of lipogenesis by the trans-10, cis-12 isomer.     

Effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on immune cell function in healthy humans

BACKGROUND: Animal studies have suggested that conjugated linoleic acid (CLA), a natural component of ruminant meat and dairy products, may confer beneficial effects on health. However, little information on the effects of CLA on immune function is available, especially in humans. Furthermore, the effects of individual isomers of CLA have not been adequately investigated. OBJECTIVE: This study investigated the effects of supplementing the diet with 3 doses of highly enriched cis-9,trans-11 CLA (0.59, 1.19, and 2.38 g/d) or trans-10,cis-12 CLA (0.63, 1.26, and 2.52 g/d) on immune outcomes in healthy humans. DESIGN: The study had a randomized, double-blind, crossover design. Healthy men consumed 1, 2, and 4 capsules sequentially that contained 80% of either cis-9,trans-11 CLA or trans-10,cis-12 CLA for consecutive 8-wk periods. This regimen was followed by a 6-wk washout and a crossover to the other isomer. RESULTS: Both CLA isomers decreased mitogen-induced T lymphocyte activation in a dose-dependent manner. There was a significant negative correlation between mitogen-induced T lymphocyte activation and the proportions of both cis-9,trans-11 CLA and trans-10,cis-12 CLA in peripheral blood mononuclear cell lipids. However, CLA did not affect lymphocyte subpopulations or serum concentrations of C-reactive protein and did not have any consistent effects on ex vivo cytokine production. CONCLUSION: CLA supplementation results in a dose-dependent reduction in the mitogen-induced activation of T lymphocytes. The effects of cis-9,trans-11 CLA and trans-10,cis-12 CLA were similar, and there was a negative correlation between mitogen-induced T lymphocyte activation and the cis-9,trans-11 CLA and trans-10,cis-12 CLA contents of mononuclear cells.     

Daily intake of conjugated linoleic acid-enriched yoghurts: effects on energy metabolism and adipose tissue gene expression in healthy subjects

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. The present study was designed to determine whether 14-week CLA supplementation as triacylglycerols (3.76 g) with a 50 : 50 combination of the two main isomers (35 % cis-9, trans-11 and 35 % trans-10, cis-12) added to flavoured yoghurt-like products was able to alter body composition in healthy subjects and to alter the expression of several key adipose tissue genes (PPAR gamma, lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and uncoupling protein 2 (UCP-2)). Forty-four healthy subjects were randomly assigned to consume daily either a CLA-supplemented yoghurt-like product or a placebo yoghurt for 98 d. There were no significant effects of CLA supplementation on body weight, fat mass or free fat mass. Basal energy expenditure expressed as kg free fat mass increased significantly in the CLA group (123.3 (SEM 2.5) kJ/kg free fat mass per d on day 98 v. 118.7 (SEM 2.3) kJ/kg free fat mass per d on day 0, P = 0.03). PPAR gamma mRNA gene expression increased significantly with CLA supplementation (53 (SEM 20) %, P < 0.01) and a significant reduction in mRNA levels of HSL was observed ( - 42 (SEM 7) %, P = 0.01). The levels of UCP-2 and LPL mRNA were not affected. The present results suggest that a 98 d supplementation diet with a 50 : 50 mixture of the two CLA isomers cis-9, trans-11 and trans-10, cis-12 in a dairy product was unable to alter body composition, although a significant increase in the RMR has been induced. Moreover, changes in mRNA PPAR gamma and HSL in adipose tissue were recorded.     

Duodenal and milk trans octadecenoic acid and conjugated linoleic acid (CLA) isomers indicate that postabsorptive synthesis is the predominant source of cis-9-containing CLA in lactating dairy cows

Duodenal and milk samples obtained from lactating cows in a previous study were analyzed to compare the content and isomer distribution of conjugated linoleic acids (CLA) and trans-18:1 fatty acids (tFA). Four diets containing either low [25 g/100 g dry matter (DM)] or high (60 g/100 g DM) forage were fed with or without 2% added buffer to four multiparous Holstein dairy cows in a 2 x 2 factorial, 4 x 4 Latin square design with 3-wk experimental periods. Duodenal flows of CLA were low (1.02-1.84 g/d), compared with that of tFA (57-120 g/d), regardless of diet. The greatest amounts of CLA and tFA, as well as the greatest proportions of trans-10-18:1 (P < 0.02), and cis-9, trans-11 (P < 0.01) and trans-10, cis-12 CLA (P < 0.01) were in the duodenal flow of cows fed the low forage unbuffered diet. In milk fat, tFA were increased by the low forage unbuffered diet and the trans-10-18:1 (P < 0.02) replaced trans-11-18:1 as the major 18:1 isomer. Milk CLA secretion (7.2-9.1 g/d) was greater (P < 0.001) than that in the duodenal flow with each diet. This was due to the increase in cis-9, trans-11-18:2 and trans-7, cis-9 CLA, resulting most likely from endogenous synthesis via Delta9-desaturation of ruminally derived tFA. For other CLA isomers, duodenal flow was always greater than milk secretion, suggesting that they essentially were produced in the rumen.     

Conjugated linoleic acid in combination with supplemental dietary fat alters pork fat quality

Interest in fortification of human foods, including pork, with conjugated linoleic acid (CLA) is growing and may provide benefits as a neutraceutical based on research evaluating CLA as an anticarcinogen, immune modulator, antiatherogenic agent and a body composition modulator. This study evaluated the combined effects of dietary CLA and supplemental fat source on growth, fatty acid composition and belly quality of lean genotype gilts (n = 144). Pigs (49.3 kg) were randomly assigned to six diets (3 x 2 factorial) varying in supplemental fat (none, 4 g/100 g yellow grease or 4 g/100 g tallow) and linoleic acid [1 g/100 g corn oil (CO) or 1 g/100 g CLA (CLA-60)] for 47 d. Both the cis-9, trans-11 and the trans-10, cis-12 isomers of CLA were increased in belly and longissimus fat depots from pigs fed CLA, and that increase was up to 92% greater when CLA was fed with 4 g/100 g supplemental fat (fat source x linoleic acid interaction, P < 0.05). Pigs fed CLA had a greater concentration of 18:0 and less 18:1 cis-9 (P < 0.01) in various fat depots, suggesting a reduction in Delta(9) desaturase activity. The iodine value of belly fat from pigs consuming tallow and CLA combined was reduced to 62.0 from an initial value of 70.4. CLA supplementation also increased belly weights (P < 0.05). CLA did not affect longissimus muscle area, backfat depth and the percentage of fat-free lean (P > 0.10), but it increased the subjective intramuscular fat score by 18.8% (P < 0.01). In conclusion, CLA enrichment of pork products may be enhanced when combined with additional supplemental dietary fat, and together with tallow can be used to increase the saturated fatty acid content of pork.     

Adenoma growth stimulation by the trans-10, cis-12 isomer of conjugated linoleic acid (CLA) is associated with changes in mucosal NF-kappaB and cyclin D1 protein levels in the Min mouse

Conjugated linoleic acid (CLA) is a term used to describe the different conjugated isomers of linoleic acid. CLA has been found to be anticarcinogenic in mammary cancer, but its effects on colon carcinogenesis are still inconclusive. In this study, the isomer-specific effects of the cis-9, trans-11 and trans-10, cis-12 CLA isomers were investigated in the Min mouse model for intestinal carcinogenesis. The Min mice (n = 10/group) were fed either an AIN-93G control diet or a diet containing 1 g/100 g cis-9, trans-11 or trans-10, cis-12 CLA for 8 wk. The number and size of adenomas were measured and the proteins from the small intestinal tissues extracted for immunoblotting analysis. The number of adenomas did not differ, but the size of the adenomas was greater in the distal part of the small intestine in mice fed the trans-10, cis-12 isomer than in controls (1.19 +/- 0.16 vs. 0.94 +/- 0.21 mm, mean +/- SD, P < 0.01). The same isomer caused an increase in lipid peroxidation, measured as urinary 8-iso-prostaglandin (PG)F(2alpha). Nuclear p65 protein of the mucosal tissue was not detectable in the trans-10, cis-12 group, which differed (P < 0.05) from the control group. Cyclin D1, a target for the nuclear factor (NF)-kappaB pathway, was elevated in the trans-10, cis-12 group compared with the control group (P < 0.01), but cyclooxygenase-2 levels were not higher. There was no difference in beta-catenin protein levels between the groups. The results indicate that the trans-10, cis-12 isomer of CLA can act as a cancer promoter in colon carcinogenesis possibly through pathways affecting NF-kappaB and cyclin D1.     

Milk fat synthesis in dairy cows is progressively reduced by increasing supplemental amounts of trans-10, cis-12 conjugated linoleic acid (CLA)

Conjugated linoleic acid (CLA) supplements containing a variety of isomers reduce milk fat yield. We have recently identified trans-10, cis-12 CLA as the isomer responsible for inhibiting milk fat synthesis in dairy cows. Our objectives were to determine milk fat yield and fatty acid composition responses to different doses of trans-10, cis-12 CLA. Multiparous Holstein cows (n = 4) were used in a 4 x 4 Latin square design. Treatments consisted of a 5-d abomasal infusion of four doses of trans-10, cis-12 CLA, i.e., 0.0, 3.5, 7.0 and 14.0 g/d. Milk fat yield was decreased 25, 33, and 50%, and milk fat concentration was reduced 24, 37 and 46% when cows received 3.5, 7.0 and 14.0 g/d of trans-10, cis-12 CLA, respectively. Feed intake, milk yield, and milk protein content and yield were unaffected by treatment. Milk fatty acid composition revealed that de novo synthesized fatty acids (short and medium chain) were extensively reduced when cows received the two highest doses, but at the low dose (3.5 g/d), decreases in de novo synthesized fatty acids and preformed fatty acids were similar. Changes in milk fatty acid composition also demonstrated that (9)-desaturase activity was inhibited at the two high doses of trans-10, cis-12 CLA, but was unaffected by the low dose. Results indicate minimal quantities of trans-10, cis-12 CLA (0.016% of dietary dry matter) markedly inhibited milk fat synthesis (25% reduction) and that a curvilinear reduction in milk fat yield occurred with increasing quantities of trans-10, cis-12 CLA.     

Effects of milk supplementation with conjugated linoleic acid (isomers cis-9, trans-11 and trans-10, cis-12) on body composition and metabolic syndrome components

The effects of conjugated linoleic acid (CLA) on body weight and body composition in man are controversial. The aim of this study was to investigate the effects of milk supplementation with CLA on body composition and on the biochemical parameters of the metabolic syndrome. This was a randomised, double-blind, placebo-controlled trial. Subjects were randomised to a daily intake of 500 ml milk supplemented with 3 g CLA (using a mixture of the bioactive isomers cis-9, trans-11 and trans-10, cis-12, marketed as Tonalin, Naturlinea; Central Lechera Asturiana) or placebo for 12 weeks. Sixty healthy men and women (aged 35-65 years) with signs of the metabolic syndrome participated (BMI 25-35 kg/m2). Dual-energy X-ray absorptiometry was used to measure body composition (week 0 baseline and week 12). Total fat mass in the CLA-milk subgroup with a BMI < or = 30 kg/m2 decreased significantly while no changes were detected in the placebo group (approximately 2 %, P = 0.01). Trunk fat mass showed a trend towards reduction (approximately 3 %, P = 0.05). CLA supplementation had no significant effect on the parameters of the metabolic syndrome, nor was it associated with changes in haematological parameters or renal function. The supplementation of milk with 3 g CLA over 12 weeks results in a significant reduction of fat mass in overweight but not in obese subjects. CLA supplementation was not associated with any adverse effects or biological changes.     

Conjugated linoleic acid induces mast cell recruitment during mouse mammary gland stromal remodeling

Conjugated linoleic acid (CLA) is a dietary chemopreventive agent that induces apoptosis in the mammary adipose vascular endothelium and decreases mammary brown adipose tissue (BAT) and white adipose tissue (WAT). To determine onset and extent of stromal remodeling, we fed CD2F1/Cr mice diets supplemented with 1 or 2 g/100 g mixed CLA isomers for 1-7 wk. BAT loss, collagen deposition, and leukocyte recruitment occurred in the mouse mammary fat pad, coincident with an increase in parenchymal-associated mast cells in mice fed both levels of CLA. Feeding experiments with purified isomers (0.5 g/100 g diet) demonstrated that these changes were induced by trans-10, cis-12 CLA (10,12-CLA), but not by cis-9, trans-11 CLA (9,11-CLA). This stromal remodeling did not require tumor necrosis factor (TNF)-alpha, a major cytokine in mast cells, as TNF-alpha null mice demonstrated collagen deposition, increased leukocytes, and BAT loss in the mammary fat pad in response to 10,12-CLA. To test the hypothesis that mast cells recruited in response to 10,12-CLA were required for stromal remodeling, Steel mice (WBB6F1/J-kit(W)/kit(W-V)), which lack functional mast cells, were examined for their stromal response to 10,12-CLA. Both wild-type and Steel mice showed a significantly increased leukocytic adipose infiltrate, collagen deposition, and decreased adipocyte size, although BAT was maintained in Steel mice. These results demonstrate that 10,12-CLA induces an inflammatory and fibrotic phenotype in the mouse mammary gland stroma that is independent of TNF-alpha or mast cells and suggest caution in the use of 10,12-CLA for breast cancer chemoprevention.     

Effects of conjugated linoleic acid (CLA) isomers on lipid levels and peroxisome proliferation in the hamster

Effects of the conjugated linoleic acid (CLA) isomers cis-9, trans-11 (c9,t11 CLA) and trans-10, cis-12 (t10,c12 CLA) on lipid metabolism and markers of peroxisome proliferation were investigated in hamsters fed on purified diets containing 30% energy as fat and 0.1 g cholesterol/kg for 8 weeks. Four groups (n 32 each) received diets without CLA (control), with a mixture of equal amounts of c9,t11 and t10,c12 CLA (CLA mix), with c9,t11 CLA, and with t10,c12 CLA. The total amount of CLA isomers was 1.5% energy of 6.6g/ kg diet. CLA was incorporated into glycerides and exchanged for linoleic acid in the diet. Compared with the control, the CLA mix and t10,c12 CLA decreased fasting values of LDL- (21 and 18% respectively) and HDL-cholesterol (8 and 11%), increased VLDL-triacylglycerol (80 and 61%, and decreased epididymal fat pad weights (9 and 16%), whereas c9,t11 CLA had no significant effects. All CLA preparations increased liver weight, but not liver lipids. However, the increase in liver weight was much less in the c9,t11 CLA group (8%) than in the other two groups (25%) and might have been caused by the small amount of t10,c12 CLA present in the c9,t11 CLA preparation. Liver histology revealed that increased weight was due to hypertrophy. Markers of peroxisome proliferation, such as cyanide-insensitive palmitoyl CoA oxidase (EC 1.3.3.6) and carnitine acetyl transferase (EC 2.3.1.7) activities, were not increased by CLA. Both c9,t11 CLA and t10,c12 CLA were incorporated into phospholipids and triacylglycerols, but t10,c12 CLA only about half as much as c9,t11 CLA. In addition, linoleic acid and linolenic acid concentrations were lower in lipids of the t10,c12 CLA group compared with the c9,t11 CLA group. These data suggest that t10,c12 CLA stimulated the oxidation of all C18 polyunsaturated fatty acids. The results indicate that the t10,c12 CLA isomer, and not the so-called natural CLA isomer (c9,t11), is the active isomer affecting lipid levels in hamsters.     

Effects of trans-10, cis-12 conjugated linoleic acid on the expression of uncoupling proteins in hamsters fed an atherogenic diet

It is known that conjugated linoleic acid (CLA) feeding decreases body adiposity but the mechanisms involved are not clear. The aim of this study was to analyse whether alterations in uncoupling protein (UCP) expression in white and brown adipose tissues (WAT and BAT, respectively) and in skeletal muscle may be responsible for the effect of trans-10, cis-12 CLA on the size of body fat depots in hamsters. Animals were divided into three groups and fed an atherogenic diet with different amounts of trans-10, cis-12 CLA (0 control, 0.5, or 1 g/100 g diet) for 6 weeks. CLA feeding reduced adipose depot weights, but had no effect on body weight. Leptin mRNA expression decreased in both subcutaneous and perirenal WAT depots, in accordance with lower adiposity, whereas resistin mRNA expression was not changed. Animals fed CLA had lower UCP1 mRNA levels in BAT (both doses of CLA) and in perirenal WAT (the low dose), and lower UCP3 mRNA levels in subcutaneous WAT (the high dose). UCP2 mRNA expression in WAT was not significantly affected by CLA feeding. Animals fed the high dose of CLA showed increased UCP3 and carnitine palmitoyl transferase-I (CPT-I) mRNA expression levels in skeletal muscle. In summary, induction of UCP1 or UCP2 in WAT and BAT is not likely to be responsible for the fat-reduction action of CLA, but the increased expression of UCP3 in skeletal muscle, together with a higher expression of CPT-I, may explain the previously reported effects of dietary CLA in lowering adiposity and increasing fatty acid oxidation by skeletal muscle.