trans-10-cis-12-conjugated-linoleic-acid and 9-11-linoleic-acid

Conjugated linoleic acid (CLA) is a popular supplement believed to enhance immune function, body composition and insulin sensitivity, but results of scientific studies investigating its effects are conflicting. The isomer- and tissue-specific effects of CLA may explain these conflicting results. Therefore, this study quantified the incorporation of the c9t11 and t10c12 CLA isomers into adipose tissue and skeletal muscle in response to supplementation in healthy, regularly-exercising, non-obese persons. The CLA group (n = 14) ingested 3.9 g per day CLA (50:50 t9c11:c10t12) and the placebo group (n = 11) 3.9 g per day high-oleic-acid sunflower oil for 12 weeks. Following supplementation, the t10c12 isomer was incorporated into adipose tissue triacylglycerol (P < 0.001), and the c9t11 isomer tended to increase in skeletal muscle phospholipids (P = 0.056). Therefore, human adipose tissue and skeletal muscle are enriched with CLA in an isomer-specific manner.

Topics: Adipose Tissue; Adult; Double-Blind Method; Female; Humans; Linoleic Acids, Conjugated; Male; Middle Aged; Muscle, Skeletal

Two conjugated linoleic acid (CLA) isomers, cis-9, trans-11 (CLAc9t11) and trans-10, cis-12 (CLAt10c12), reduce inflammation in a number of animal models, including collagen-induced arthritis (CA). However, little is known about the ability of individual CLA isomers to prevent autoimmune disease onset. Evidence that mixed isomer CLA drives T helper cell (Th) 1 responses suggests that CLA, or a specific isomer, exacerbates onset of Th1 autoimmune diseases. In two experiments, we examined if prior dietary exposure to CLAt10c12 (experiment 1) or CLAc9t11 (experiment 2) affected the incidence or severity of CA. DBA/1 mice were fed a semi purified diet with either 6% corn oil (CO, w/w), 5.75% CO plus 0.25% CLAt10c12, or 5.5% CO plus 0.5% CLAc9t11 prior to arthritis development. Arthritis incidence and severity, anti-collagen antibodies, paw cytokines, and hepatic fatty acids were measured. CLAt10c12 had no effect on arthritis incidence but increased arthritic severity (42%, P = 0.02); however, CLAc9t11 decreased arthritis incidence 39% compared to CO fed mice (P = 0.01), but had no effect on disease severity. CLAt10c12-induced increase in anti-collagen type II IgG antibodies may be a mechanism by which this isomer increased arthritic severity, and CLAc9t11-induced increase in Th2 paw cytokines (IL-4 and IL-10, P ≤ 0.04) may explain how CLAc9t11 reduced the arthritis incidence. While both isomers are well known to reduce inflammation in arthritic mice, these new data suggest isomer differences when fed prior to autoimmune disease.

Topics: Animals; Arthritis, Experimental; Corn Oil; Cytokines; Dietary Fats; Drug Therapy, Combination; Linoleic Acids, Conjugated; Mice; Mice, Inbred DBA; Random Allocation; Severity of Illness Index; Treatment Outcome

High-density lipoproteins (HDLs) are atheroprotective because of their role in reverse cholesterol transport. The intestine is involved in this process because it synthesizes HDL, removes cholesterol from plasma and excretes it into the lumen. We investigated the role of selected dietary fatty acids on intestinal cholesterol uptake and HDL functionality. Caco-2 monolayers grown on Transwells were supplemented with either palmitic, palmitoleic, oleic, linoleic, docosahexaenoic, eicosapentaenoic, arachidonic or conjugated linoleic acids (CLAs): c9,t11-CLA; t9,t11-CLA; c10,t12-CLA. Cells synthesized HDL in the basolateral compartment for 24 h in the absence or presence of an antibody to SR-BI (aSR-BI), which inhibits its interaction with HDL. Free cholesterol (FC) accumulated to a greater extent in the presence than in the absence of aSR-BI, indicating net uptake of FC by SR-BI. Uptake's efficiency was significantly decreased when cells were treated with c9,t11-CLA relative to the other fatty acids. These differences were associated with lower HDL functionality, since neither SR-BI protein expression nor expression and alternative splicing of other genes involved lipid metabolism were affected. Only INSIG2 expression was decreased, with no increase of its target genes. Increasing pre-β-HDL synthesis, by inducing ABCA1 and adding APOA1, resulted in reduced uptake of FC by SR-BI after c9,t11-CLA treatment, indicating reduced functionality of pre-β-HDL. Conversely, treatment with c9,t11-CLA resulted in a greater uptake of FC and esterified cholesterol from mature HDL. Therefore, Caco-2 monolayers administered c9,t11-CLA produced a nonfunctional pre-β-HDL but took up cholesterol more efficiently via SR-BI from mature HDL.

Topics: Alternative Splicing; Biological Transport; Caco-2 Cells; CD36 Antigens; Cell Polarity; Cholesterol Esters; Cholesterol, Dietary; Cholesterol, HDL; Enterocytes; Enterohepatic Circulation; Gene Expression Regulation; High-Density Lipoproteins, Pre-beta; Humans; Intestinal Absorption; Intracellular Signaling Peptides and Proteins; Kinetics; Linoleic Acids, Conjugated; Lipoproteins, HDL; Membrane Proteins; Stereoisomerism

Conjugated linoleic acid (CLA) is thought to have anti-proliferative and anti-inflammatory properties, but its effect on cancer cachexia is unknown. Two effects were here investigated: that of CLA on inflammatory mediator production in human lung cancer cells, and that of reduced mediators on the myogenic differentiation of murine muscle C2C12 cells. The latter cells were grown in medium conditioned by human lung cancer A427 cells, with or without CLA, to mimic only the effect of molecules released from the tumor "in vivo", excluding the effect of host-produced cachectic factors. The results obtained show that CLA was found to reduce the production of tumor necrosis factor-α, interleukin (IL)-1β and prostaglandin E2 (PGE2), but had no effect on IL-6 production. The mechanisms underlying the effect of CLA on cytokine or PGE2 release in A427 cells are probably mediated by activation of peroxisome proliferator-activated receptor (PPAR)α, which increased at 24 h CLA treatment. In turn, the reduced content of inflammatory mediators in medium conditioned by A427 cells, in the presence of CLA, allowed muscle cells to proliferate, again by inducing PPAR. The involvement of PPARα was demonstrated by treatment with the antagonist MK-886. The findings demonstrate the anti-inflammatory and myogenic action of CLA and point to its possible application as a novel dietary supplement and therapeutic agent in inflammatory disease states, such as cachexia.

Topics: Animals; Anticarcinogenic Agents; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Culture Media, Conditioned; Dinoprostone; Horses; Indoles; Inflammation Mediators; Interleukin-1; Interleukin-6; Linoleic Acids, Conjugated; Lung; Lung Neoplasms; Mice; Muscle Cells; Peroxisome Proliferator-Activated Receptors

Conjugated linoleic acid (CLA) has been shown to have a variety of biological activities. However, the effects of CLA on the proliferation of neural progenitor cells (NPCs) are not clear. The objective of this study was to determine the effects of cis-9 trans-11 CLA and trans-10 cis-12 CLA, the predominant individual isomers, on the proliferative activity of NPCs in vitro. Cell counts showed that treatment of NPCs with cis-9 trans-11 CLA increased the cell number in a dose- and time- dependent manner while significant inhibition effect of trans-10 cis-12 CLA was observed. Western blot analysis revealed the elevated expression of cyclin D1 induced by cis-9 trans-11 CLA treatment and the decreased expression of cyclin D1 by trans-10 cis-12 CLA treatment in NPCs. Cyclin D1-siRNA transfection significantly inhibited the promotion of cell proliferation by cis-9 trans-11 CLA. In addition, trans-10 cis-12 CLA inhibited the phosphorylation of protein kinase B (PKB/Akt), while cis-9 trans-11 CLA had no effect on phospho Akt levels. Furthermore, immunofluorescence assay showed that after CLA treatment, the cells retained their functional characteristics of neural progenitors. These results indicated that cis-9 trans-11 CLA can effectively enhance the proliferation of hADSCs. The effect of cis-9 trans-11 CLA may be associated with the up-regulation of cyclin D1 expression.

Topics: Animals; Cell Proliferation; Cells, Cultured; Cyclin D1; Isomerism; Linoleic Acids, Conjugated; Neural Stem Cells; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; RNA Interference; RNA, Small Interfering

Conjugated linoleic acid (CLA) has been shown to reduce body fat mass in various experimental animals. It is valuable to identify its influence on enzymes involved in energy expenditure, apoptosis, fatty acid oxidation and lipolysis. We investigated isomer-specific effects of high dose, long treatment of CLA (75.4 μmol/L, 8 days) on protein and gene expression of these enzymes in cultured 3T3-L1 cells. Proteomics identified significant up- or down-regulation of 52 proteins by either CLA isomer. Protein and gene expression of uncoupling protein (UCP) 1, UCP3, perilipin and peroxisome proliferator-activated receptor (PPAR) α increased whereas UCP2 reduced for both CLA isomers. And eight-day treatment of trans-10,cis-12 CLA, but not cis-9,trans-11 CLA, significantly up-regulated protein and mRNA levels of PKA (P<.05), CPT-1 and TNF-α (P<.01). Compared to protein expression, both isomers did not significantly influence the mRNA expression of HSL, ATGL, ACO and leptin. In conclusion, high-dose, long treatment of cis-9,trans-11 CLA did not promote apoptosis, fatty acid oxidation and lipolysis in adipocytes, but may induce an increase in energy expenditure. trans-10,cis-12 CLA exhibited greater influence on lipid metabolism, stimulated adipocyte energy expenditure, apoptosis and fatty acid oxidation, but its effect on lipolysis was not obvious.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Carrier Proteins; Down-Regulation; Ion Channels; Leptin; Linoleic Acids, Conjugated; Lipid Metabolism; Lipolysis; Mice; Mitochondrial Proteins; Oxidation-Reduction; Perilipin-1; Phosphoproteins; PPAR alpha; Proteomics; RNA, Messenger; Uncoupling Protein 1; Uncoupling Protein 3; Up-Regulation

Dietary supplementation with conjugated linoleic acid (CLA) has been shown to reduce body fat mass. To investigate the effects of individual CLA isomers on the fatty acid profiles of lipogenic (liver and white adipose) and lipid sensitive (erythrocyte) tissues, BALB/c mice were fed with 1 of 2 diets supplemented with either a c9,t11-CLA-enriched and t10,c12-CLA-free or a CLA-mixture containing both isomers in equal amounts (1% w/w of the diet) for 5 weeks. A control group was fed with a diet enriched in sunflower oil to energy balance the CLA. Compared to the t10,c12-CLA-free and the control diets, we observed a significant reduction of adipose tissue accompanied by fatty livers in the CLA-mix-fed group. These alterations in body fat distribution entailed a conspicuous shift of the fatty acid profiles of adipose tissue and livers. Liver enlargement was mainly caused by accumulation of C18 monoenes that accounted for 67 ± 1% of total fatty acid methyl esters. The significant reduction of the 18:0/18:1 desaturation index in the liver upon CLA-mix diet indicated high stearoyl-CoA desaturase activity. In contrast, reduction in white adipose tissue was largely driven by percental reduction of monounsaturated fatty acids (p ≤ 0.001). 16:0/ 16:1 and 18:0/18:1 desaturation indices for white adipose tissue significantly increased, suggesting an inhibition of stearoyl-CoA desaturase upon CLA-mix diet. The fatty acid profile of the erythrocytes widely reflected that of livers, depending on the supplemented diet. These profound changes in fatty acid composition of lipogenic organs due to t10,c12-CLA intake may be the consequence of functional alterations of lipid metabolism.

Topics: Adipose Tissue, White; Animals; Dietary Fats; Dietary Supplements; Erythrocytes; Fatty Liver; Female; Humans; Linoleic Acids, Conjugated; Lipid Metabolism; Lipodystrophy; Liver; Mice; Mice, Inbred BALB C; Random Allocation; Stearoyl-CoA Desaturase

Growing female obese Zucker (fa/fa) rats were treated (via intragastric gavage) for 21 d with either a (i) vehicle [corn oil; 0.9 g/kg body weight (BW)], (ii) CLA mixture [50:50; trans-10, cis-12 and cis-9, trans-11 CLA], (iii) cis-9,trans-11 CLA, or (iv) trans- 10, cis-12 CLA (CLA treatments at 1.5 g CLA/kg BW). Compared with controls, average daily gain (g/d) was reduced 24 and 44% by the CLA mixture and trans-10, cis-12 CLA, respectively. There was no treatment effect on average whole-body (minus heart and liver) composition (dry matter basis): fat (70.2%), protein (21.0%), and ash (4.3%). Compared with animals treated with cis-9,trans-11 CLA, obese Zucker rats treated with trans-10, cis-12 and the CLA mixture had 7.8% more carcass water. Treatment had no effect on heart or liver weights or on heart or liver weights as a percentage of body weight, but compared with the other treatments trans-10, cis-12 CLA increased liver lipid content by 33%. Hepatic lipid ratios of 16:1/16:0 and 18:1/18:0 (a proxy for delta9-desaturase capability) were not affected by treatment (0.1 and 0.6, respectively). Similar to previous reports, CLA increased hepatic lipid content and altered both liver and carcass FA composition (i.e., reduced arachidonic acid content), but the ability of CLA to manipulate body composition in obese Zucker rats remains questionable.

Topics: Adipose Tissue; Animals; Body Composition; Diet; Fatty Acids; Female; Growth; Isomerism; Linoleic Acids, Conjugated; Obesity; Organ Size; Rats; Rats, Zucker