T11 Conjugated Linoleic Acid Isomer Research Articles

CLA and EPA inhibit LPS-induced prostaglandin release from bovine endometrial cells through an NF-κB-dependent signaling mechanism

Although their action in antagonizing arachidonic acid metabolism is a key antiinflammatory effect of conjugated linoleic acid (CLA) and omega-3 polyunsaturated fatty acids (n-3 PUFA), these molecules have other antiinflammatory effects that might occur upstream of altered eicosanoid production. We examined the effects of two CLA isomers (c9,t11 and t10,c12 isomers), n-3 PUFA (EPA and DHA), and κNF-κB inhibitor (ammonium pyrrolidine dithiocarbamate (PDTC)) on lipopolysaccharide (LPS)-induced secretion of prostaglandins (PGE 2 and PGF 2a ) by bovine endometrial (BEND) cells. LPS increased PGE 2 and PGF 2a concentrations in BEND cell- conditioned media in a concentration- and time-dependent manner. The c9,t11 CLA isomer and EPA decreased prostaglandin response to LPS. Addition of PDTC, alone or in combination with c9,t11 CLA or EPA, inhibited LPS-induced eicosanoid release into the culture medium. Results indicate that the c9,t11 CLA isomer and EPA inhibit the endometrial prostaglandin release in cattle and that these molecules may act through an NF-κB signaling mechanism.

Dietary CLA Combined with Palm Oil or Ovine Fat Differentially Influences Fatty Acid Deposition in Tissues of Obese Zucker Rats

The effect of dietary conjugated linoleic acid (CLA) supplementation in combination with fat from vegetable versus animal origin on the fatty acid deposition, including that of individual 18:1 and 18:2 (conjugated and non-conjugated) isomers, in the liver and muscle of obese rats was investigated. For this purpose, 32 male Zucker rats were randomly assigned to one of four diets containing palm oil or ovine fat, supplemented or not with 1% of 1:1 cis(c)9,trans(t)11 and t10,c12 CLA isomers mixture. Total fatty acid content decreased in the liver and muscle of CLA-fed rats. In the liver, CLA increased saturated fatty acids (SFA) in 11.9% and decreased monounsaturated fatty acids (MUFA) in 6.5%. n-3 Polyunsaturated fatty acids (PUFA) relative proportions were increased in 30.6% by CLA when supplemented to the ovine fat diet. In the muscle, CLA did not affect SFA but decreased MUFA and PUFA percentages. The estimation of Δ9-indices 16 and 18 suggested that CLA inhibited the stearoyl-CoA desaturase activity in the liver (a decrease of 13-38%), in particular when supplemented to the ovine fat diet. Concerning CLA supplementation, the t10,c12 isomer percentage was 60-80% higher in the muscle than in the liver. It is of relevance that rats fed ovine fat, containing bio-formed CLA, had more c9,t11 CLA isomer deposited in both tissues than rats fed palm oil plus synthetic CLA. These results highlight the importance to further clarify the biological effects of consuming foods naturally enriched in CLA, alternatively to CLA dietary supplementation.

The Role of Conjugated Linoleic Acid in Breast Cancer Growth and Development

Conjugated linoleic acid (CLA) consists of a group of naturally occurring and synthetic positional and geomet- ric (cis-trans) stereoisomers of the polyunsaturated fatty acid linoleic acid. The cis-9,trans-11 (c9,t11) CLA isomer (the most prevalent form found in ruminant-derived foods) and the trans-10,cis-12 (t10,c12) CLA isomer (present in commer- cial preparations) are the two most widely studied CLA isomers in breast cancer. Studies using both animal and cell cul- ture models indicate that these CLA isomers, when added to the diet or included in the cell culture medium, inhibit mam- mary tumour initiation, promotion and progression in rodents, and alter tumour cell viability in vitro. The mechanism of CLA's anticancer effect is not well understood, but may involve interference with the cell cycle, induction of apoptosis, modulation of gene expression via the activation of peroxisome proliferator-activated receptors, lipid peroxidation, modu- lation of the tumour microenvironment, changes to the structure and/or function of the cell membrane, and interference with growth factor receptor signaling. A greater understanding of the mechanism of action of CLA will support the devel- opment of clinical trials to evaluate the potential effectiveness of CLA in the treatment of breast cancer.

Effects of Conjugated Linoleic Acid on Myogenic and Inflammatory Responses in a Human Primary Muscle and Tumor Coculture Model

The antiproliferative and anti-inflammatory properties of conjugated linoleic acid (CLA) make it a potentially novel treatment in chronic inflammatory muscle wasting disease, particularly cancer cachexia. Human primary muscle cells were grown in coculture with MIA PaCa-2 pancreatic tumor cells and exposed to varying concentrations of c9,t11 and t10,c12 CLA. Expression of myogenic (Myf5, MyoD, myogenin, and myostatin) and inflammatory genes (CCL-2, COX-2, IL-8, and TNF-α) were measured by real-time PCR. The t10,c12 CLA isomer, but not the c9,t11 isomer, significantly decreased MIA PaCa-2 proliferation by between 15% and 19%. There was a marked decrease in muscle MyoD and myogenin expression (78% and 62%, respectively), but no change in either Myf5 or myostatin, in myotubes grown in coculture with MIA PaCa-2 cells. CLA had limited influence on these responses. A similar pattern of myogenic gene expression changes was observed in myotubes treated with TNF-α alone. Several-fold significant increases in CCL-2, COX-2, IL-8, and TNF-α expression in myotubes were observed with MIA PaCa-2 coculture. The c9,t11 CLA isomer significantly decreased basal expression of TNF-α in myotubes and could ameliorate its tumor-induced rise. The study provides insight into the anti-inflammatory and antiproliferative actions of CLA and its application as a therapeutic agent in inflammatory disease states.

Optimization of a reconstituted skim milk based medium for enhanced CLA production by bifidobacteria

To determine the effect of a range of supplements on the bioconversion of linoleic acid to conjugated linoleic acid (CLA) by Bifidobacterium breve NCIMB 702258 in reconstituted skim milk (RSM). Seven supplements (yeast extract, casein hydrolysate, tryptone, l-cysteine hydrochloride, sodium acetate, sodium butyrate and sodium propionate) were identified as increasing the bioconversion of linoleic acid to c9, t11 CLA. Using these supplements, the percentage bioconversion of linoleic acid (0.35 mg ml(-l)) to the c9, t11 CLA isomer was elevated from 15.5 +/- 1.1% in 20% RSM (w/v) to 48.1 +/- 2.2% in the supplemented RSM. Through additional supplementation of 20 mg m1(-1) inulin and optimization of inoculum and linoleic acid concentration, the percentage bioconversion to c9, t11 CLA was increased to 55.0 + 3.2%. Through supplementation, the concentration of CLA produced by bifidobacteria in RSM can be increased to levels comparable to those observed in the synthetic medium cys-MRS. The impact of 22 supplements on the production of the c9, t11 CLA isomer by the strain B. breve NCIMB 702258 in milk has been determined. The results provide an understanding of the factors, which influence CLA production by bifidobacteria in RSM.

Diet supplementation with the cis-9,trans-11 conjugated linoleic acid isomer affects the size of adipocytes in Wistar rats

Previous reports have demonstrated that conjugated linoleic acid (CLA) acts on body fat accumulation in a variety of animal models. The aim of the present study was to investigate the effect of cis (c)-9,trans (t)-11 and t10,c12 CLA isomers on the number and size of adipocytes from the inguinal and retroperitoneal fats in Wistar male rats. A 5.1% palm oil-based diet was supplemented with CLA isomers as follows: 0.6% of c9,t11, 0.6% of t10,c12, 1.3% of c9,t11 and t10,c12 isomers in mixture, and a control nonsupplemented group for comparative purposes. Fat tissues were prepared on microscope slides for histologic examination using an image-analysis software to count the number of adipocytes and measure cell sizes. The results showed that CLA isomers did not affect (P > .05) either final body and fat depot weights or serum lipids (with the exception of triacylglycerols) and adipocytokines (leptin and adiponectin). Animals fed the c9,t11 CLA isomer diet showed larger adipocytes when compared to other groups. Independently of the CLA dietary treatment, retroperitoneal fat showed larger adipocytes (3319 microm(2)) and therefore a smaller number of adipocytes per unit of area, compared to inguinal fat (3055 microm(2)). Taken together, the data suggest that a palm oil-based diet supplemented with the c9,t11 CLA isomer in Wistar rats, in contrast to the t10,c12 isomer and the mixture of both isomers, increases adipocyte dimensions in inguinal and retroperitoneal fat depots, while having a minor effect in serum lipids and adipocytokines.

Influence of slaughter season and muscle type on fatty acid composition, conjugated linoleic acid isomeric distribution and nutritional quality of intramuscular fat in Arouquesa-PDO veal

The effects of the slaughter season and muscle type on lipid and conjugated linoleic acid (CLA) contents, fatty acid composition and isomeric profile of CLA in Arouquesa veal, from calves reared according to the specifications of the protected designation of origin (PDO), were assessed. Arouquesa purebred calves ( n = 31) were raised in a traditional production system, slaughtered in early autumn (October) or late spring (June), and the longissimus dorsi and semitendinosus muscles were sampled for analysis. Arouquesa-PDO veal only showed seasonal differences in the levels of some minor fatty acids (16:1c9, 17:1c9, 18:1t, 18:3 n − 3, 20:0 and 22:4 n − 6) and CLA isomers (t12,t14, t9,t11 and c11,t13). Furthermore, significant interactions between the slaughter season and muscle type were obtained for several fatty acids and CLA isomers, total lipids and CLA, and the PUFA/SFA ratio. In both seasons, veal-PDO depicts values of pasture-fed cattle. From a human nutritional perspective, veal-PDO in both slaughter seasons has relatively high CLA contents and percentages of the c9,t11 CLA isomer, which is favourable, while the n − 6/ n − 3 ratios are within the recommended values for the human diet. In conclusion, the results suggest that intramuscular fat in Arouquesa-PDO veal has high nutritional value throughout the year.

The effects of t10,c12 CLA isomer compared with c9,t11 CLA isomer on lipid metabolism and body composition in hamsters

The objective of the present study was to examine the effects of two different isomers of conjugated linoleic acid (CLA), c9,t11 CLA and t10,c12 CLA, compared with linoleic acid (LA) used as control, on body composition, lipoprotein profile, hepatic lipids and fecal fat content in hamsters. Animals were assigned to the three diet groups ( n=15) during 28 days. The diet was composed of 2% of the experimental fat, and throughout the experimental protocol, the hamsters experienced similar food intake. No significant differences were noted in body weight gain among the three diet groups. However, the t10,c12 CLA-fed animals showed higher low-density lipoprotein cholesterol (LDL-C) concentrations (0.9±0.1 mmol/L) than those who ingested either LA (0.6±0.1 mmol/L) or c9,t11 CLA isomer (0.7±0.1 mmol/L), although the t10,c12 CLA consumption decreased hepatic cholesterol and triglycerides and increased fecal fat content compared with the other two groups. Under the present experimental conditions, the dietary c9,t11 CLA isomer showed no positive beneficial effect on plasma lipids. Furthermore, the t10,c12 CLA isomer induced undesirable higher LDL-C, although it reduced hepatic lipids and fat digestibility in hamsters.

Effects of cis-9,trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men

We recently showed that trans-10,cis-12 (t10,c12) conjugated linoleic acid (CLA) causes insulin resistance in obese men. However, metabolic effects of the c9,t11 CLA isomer are still unknown in obese men. Because c9,t11 CLA is the predominant CLA isomer in foods and is included in dietary weight-loss products, it is important to conduct randomized controlled studies that use c9,t11 CLA preparations. We investigated the effects of c9,t11 CLA supplementation on insulin sensitivity, body composition, and lipid peroxidation in a group at high risk for cardiovascular disease. In a randomized, double-blind, placebo-controlled study, 25 abdominally obese men received 3 g c9,t11 CLA/d or placebo (olive oil). Before and after 3 mo of supplementation, we assessed insulin sensitivity (hyperinsulinemic euglycemic clamp), lipid metabolism, body composition, and urinary 8-iso-prostaglandin F(2alpha) (a major F(2)-isoprostane) and 15-keto-dihydro-prostaglandin F(2alpha), markers of in vivo oxidative stress and inflammation, respectively. All subjects completed the study. Compared with placebo, c9,t11 CLA decreased insulin sensitivity by 15% (P < 0.05) and increased 8-iso-prostaglandin F(2alpha) and 15-keto-dihydro-prostaglandin F(2alpha) excretion by 50% (P < 0.01) and 15% (P < 0.05), respectively. The decreased insulin sensitivity was independent of changes in serum lipids, glycemia, body mass index, and body fat but was abolished after adjustment for changes in 8-iso-prostaglandin F(2alpha) concentrations. There were no differences between groups in body composition. A CLA preparation containing the purified c9,t11 CLA isomer increased insulin resistance and lipid peroxidation compared with placebo in obese men. Because c9,t11 CLA occurs in commercial supplements as well as in the diet, the present results should be confirmed in larger studies that also include women.

Dietary conjugated linoleic acid alters hepatic lipid content and fatty acid composition in broiler chickens

We examined the effect of dietary conjugated linoleic acid (CLA) on growth performance and liver composition in broiler chickens. Day-old male broiler chicks were assigned to receive a diet supplemented with corn oil (5%; n = 48) or CLA (5%; n = 48) for 21 d. Broilers fed CLA weighed less and grew at slower rates than broilers fed corn oil. Feed intake and feed conversion were higher for the corn-oil group than for the CLA dietary group. Hepatic lipid and triacylglycerol concentrations were significantly reduced by dietary CLA. The proportions of saturated fatty acids (SFA) in liver lipids increased, whereas those of monounsaturated fatty acids (MUFA) decreased with CLA supplementation. Although the total concentration of polyunsaturated fatty acids (PUFA) did not change with dietary treatment, the concentration of linoleic acid as a percentage of total methylated fatty acids decreased, and that of linolenic add increased in broilers fed CLA. The concentration of CLA isomers in liver lipids increased substantially with CLA feeding. The relative proportion of the c9,t11 CLA isomer in hepatic lipids was much higher than that of the t10,c12 or t9,t11 CLA isomers. These studies provide evidence that feeding CLA to broilers results in substantial reduction in liver fat accumulation and promotes CLA incorporation into hepatic lipid pools.

Conjugated linoleic acid biosynthesis by human-derived Bifidobacterium species.

To assess strains of Lactobacillus, Lactococcus, Pediococcus and Bifidobacterium for their ability to produce the health-promoting fatty acid conjugated linoleic acid (CLA) from free linoleic acid. In this study, strains of Lactobacillus, Lactococcus, Pediococcus and Bifidobacterium were grown in medium containing free linoleic acid. Growth of the bacteria in linoleic acid and conversion of the linoleic acid to CLA was assessed. Of the bacteria assessed, nine strains of Bifidobacterium produced the c9, t11 CLA isomer from free linoleic acid. The t9, t11 CLA isomer was also produced by some strains, but at much lower concentrations. The production of CLA by bifidobacteria exhibited considerable interspecies variation. Bifidobacterium breve and B. dentium were the most efficient CLA producers among the range of strains tested, with B. breve converting up to 65% linoleic acid to c9, t11 CLA when grown in 0.55 mg ml(-1) linoleic acid. Strains also varied considerably with respect to their sensitivity to linoleic acid. The production of CLA by probiotic bifidobacteria offers a possible mechanism for some health-enhancing properties of bifidobacteria and provides novel opportunities for the development of functional foods.

Creep-fatigue interaction in T11 boiler tube steel: Miller, G.A., Marder, A.R., Holt, S.D. and Voorhees, H.R. ASTM J. Test. Eval.19 6 (Nov 1991) 485–492

The objective of the present study was to examine the effects of two different isomers of conjugated linoleic acid (CLA), c9,t11 CLA and t10,c12 CLA, compared with linoleic acid (LA) used as control, on body composition, lipoprotein profile, hepatic lipids and fecal fat content in hamsters. Animals were assigned to the three diet groups (n=15) during 28 days. The diet was composed of 2% of the experimental fat, and throughout the experimental protocol, the hamsters experienced similar food intake. No significant differences were noted in body weight gain among the three diet groups. However, the t10,c12 CLA-fed animals showed higher low-density lipoprotein cholesterol (LDL-C) concentrations (0.9±0.1 mmol/L) than those who ingested either LA (0.6±0.1 mmol/L) or c9,t11 CLA isomer (0.7±0.1 mmol/L), although the t10,c12 CLA consumption decreased hepatic cholesterol and triglycerides and increased fecal fat content compared with the other two groups. Under the present experimental conditions, the dietary c9,t11 CLA isomer showed no positive beneficial effect on plasma lipids. Furthermore, the t10,c12 CLA isomer induced undesirable higher LDL-C, although it reduced hepatic lipids and fat digestibility in hamsters.