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Conjugated Linoleic Acid
Conjugated linoleic acid supplementation modified the body composition and serum leptin levels in weaning rats
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Prais Botelho A, Santos-Zago LF, Costa de Oliveira A.
Laboratory of Lipids, Department of Food and Nutrition, College of Food Engineering, State University of Campinas, Brasil.
Dietary supplementation with conjugated linoleic acid (CLA) may reduce body fat mass and increase lean body mass in various species. The objective of this study was to study the effects of conjugated linoleic acid (CLA) supplementation on body composition, serum leptin and triacylglycerol levels in Wistar rats. Rats received linoleic acid (group C) or conjugated linoleic acid (group AE, supplemented with AdvantEdge CLA, and group CO, supplemented with CLA One) in the concentrations of 2% of daily feed consumption. Serum leptin and triacylglycerol levels of rats were measured by means of commercial kits. After 42 days of supplementation, rats in the control group exhibited body fat contents of 53.94 +/- 6.80 g, and those in groups AE and CO had 45.43 +/- 4.86 g and 43.75 +/- 1.93 g, respectively, corresponding to a mean body fat reduction of 18%. Water, whole body protein and ash contents of rats supplemented with CLA were statistically higher relative to control group content (corresponding to a mean increasing of 7.65%; 6.5% and 12.35%, respectively). Experimental groups AE and CO, which received CLA supplementation, had statistically lower serum leptin levels (3.45 +/- 0.46 ng/mL and 3.08 +/- 0.19 ng/mL, respectively) relative to the control group (4.21 +/- 0.22 ng/mL) which received linoleic acid. Triacylglycerol levels did not change after CLA supplementation (p > 0.05). Supplementation with conjugated linoleic acid in the concentration of 2% of mean daily feed consumption was able to change body composition of rats after 42 days of experimentation.
Cosupplementation of dietary calcium and conjugated linoleic acid (CLA) improves bone mass in mice.
Park Y, Pariza MW, Park Y.
Dept of Food Science, Univ of Massachusetts Amherst, Amherst, MA 01002, USA. ypark@foodsci.umass.edu
Conjugated linoleic acid (CLA) has shown a variety of biologically beneficial effects, such as anticancer, antiatherosclerosis, antidiabetic, immunomodulating, and antiobesity effects. Its effects on reduction of body fat occur with enhancement of lean body mass and body ash; the effects of CLA on bone mass are inconsistent in mice and human studies. We hypothesized that the inconsistency of CLA's effect on ash may be linked to interaction between CLA and dietary calcium levels. We reanalyzed our previous studies, which used mice fed 0.5% CLA-containing diet with regular calcium content (0.5%) or enhanced calcium level (0.66%). Extra calcium in the diet improved CLA's effects on bone mass, particularly in male mice (P= 0.0194); without extra dietary calcium there was no effect of CLA on bone mass. This finding may help improve the efficacy of CLA to be used as a dietary supplement to be used as part of an osteoporosis prevention strategy. Further studies are needed to confirm this observation.
Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol.
Kennedy A, Overman A, Lapoint K, Hopkins R, West T, Chuang CC, Martinez K, Bell D, McIntosh MK.
Inflammation plays a role in trans-10, cis-12 (10,12) conjugated linoleic acid (CLA)-mediated delipidation and insulin resistance in adipocytes. Given the anti-inflammatory role of resveratrol (RSV), we hypothesized that RSV would attenuate inflammation and insulin resistance caused by 10,12 CLA in human adipocytes. RSV blocked 10,12 CLA induction of the inflammatory response by preventing activation of extracellular signal related kinase (ERK) and induction of inflammatory gene expression (i.e., IL-6, IL-8, IL-1ss) within 12 h. Similarly, RSV suppressed 10,12 CLA-mediated activation of the inflammatory prostaglandin (PG) pathway involving phospholipase A2, cyclooxygenase-2 (COX-2), and PGF2a. In addition, RSV attenuated 10,12 CLA increase of intracellular calcium and reactive oxygen species (ROS) associated with cellular stress, and activation of stress-related proteins (i.e., ATF3, JNK) within 12 h. 10,12 CLA-mediated insulin resistance and suppression of fatty acid uptake and triglyceride content were attenuated by RSV. Lastly, 10,12 CLA-mediated decrease of peroxisome proliferator activated receptor (PPAR) protein levels and activation of a peroxisome proliferator response element (PPRE) reporter were prevented by RSV. RSV increased the basal activity of the PPRE, suggesting RSV increases PPAR activity. Collectively, these data demonstrate for the first time that RSV prevents 10,12 CLA-mediated insulin resistance and delipidation in human adipocytes by attenuating inflammation and cellular stress and increasing PPAR activity.
Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue.
Wang LS, Huang YW, Liu S, Yan P, Lin YC.Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA. wang.774@osu.edu
BACKGROUND: Conjugated linoleic acid (CLA), a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems. In human breast cancer, the overall duration of estrogen exposure is the most important risk factor for developing estrogen-responsive breast cancer. Accordingly, it has been suggested that estrogen exposure reduces apoptosis through the up-regulation of the anti-apoptosis protein, Bcl-2. Bcl-2, an anti-apoptotic protein, regulates apoptosis and plays a crucial role in the development and growth regulation of normal and cancerous cells. Our research interest is to examine the effects of CLA on the induction of apoptosis in human breast tissues.
METHODS: The localization of Bcl-2 in both normal and cancerous human breast tissues was determined by immunohistochemical staining and the Bcl-2 protein expression was tested by western blot analysis. Co-culture of epithelial cells and stromal cells was carried out in the presence or absence of CLA to evaluate apoptosis in the context of a cell-cell interaction.
RESULTS: The results showed that both normal and cancerous breast tissues were positive for Bcl-2 staining, which was higher overall in mammary ducts but very low in the surrounding stromal compartment. Interestingly, by quantifying the western blot data, basal Bcl-2 protein levels were higher in normal breast epithelial cells than in cancerous epithelial cells. Furthermore, treatment with 17beta-estradiol (E2) stimulated growth and up-regulated Bcl-2 expression in estrogen responsive breast epithelial cells; however, these carcinogenic effects were diminished by either CLA or 4-Hydroxytamoxifen (Tam) and were suppressed further by the combination of CLA and Tam. In both one cell type cultured and co-culture systems, CLA induced cell apoptosis in ERalpha transfected MDA-MB-231 cells but not in the wild type MDA-MB-231 cells.
CONCLUSION: These data, therefore, demonstrate that ERalpha plays important roles in CLA induced apoptosis in human breast tissues.
Growth inhibition of osteosarcoma cell MG-63 by a mixture of trans,trans conjugated linoleic acid isomers: possible mechanistic actions.
Kim YS, Cerbo RM, Hah CK, Bahn KN, Kim JO, Ha YL.
Division of Applied Life Sciences, Graduated School, and Institute of Agriculture & Life Science, Gyeongsang National University, Jinju 660-701, Korea.
The growth inhibitory effect of a mixture of t,t conjugated linoleic acid isomers (t,t CLA) was investigated in the human osteosarcoma cell MG-63, with references to c9,t11 and t10,c12 CLA isomers. The t,t CLA effectively induced a cytotoxic effect in a time-dependent (0 to 6 d) and concentration-dependent (0 to 40 microM) manner, as compared to the reference and control treatments. The apoptosis and cell cycle related parameters were measured on the cells treated with 40 microM t,t CLA for 4 d. Flow cytometric analysis revealed that the t,t CLA treatment effectively increased the proportion of apoptotic cells with a low DNA content (sub G0/G1) and a marked loss of cells from the G0/G1 phase of the cell cycle, relative to other treatments. The occurrence of the characteristic morphological changes and DNA fragmentation confirmed the apoptosis. The level of Bax protein was increased, whereas the Bcl-2 expression was reduced. In addition, cytochrome c was released from the mitochondria into the cytosol, and the activation of caspase-3 led to the cleavage of poly (ADP-ribose) polymerase (PARP). Moreover, the composition of linoleic and arachidonic acids in membrane was decreased by increase in t,t CLA. These findings suggest that t,t CLA incorporation in membrane activates a mitochondria-mediated apoptosis pathway that can enhance the antiproliferative effect of t,t CLA in the osteosarcoma cells.
Conjugated linoleic acid isomers and cancer.
Kelley NS, Hubbard NE, Erickson KL.
Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, CA 95616-8643, USA.
We reviewed the literature regarding the effects of conjugated linoleic acid (CLA) preparations enriched in specific isomers, cis9, trans11-CLA (c9, t11-CLA) or trans10, cis12-CLA (t10, c12-CLA), on tumorigenesis in vivo and growth of tumor cell lines in vitro. We also examined the potential mechanisms by which CLA isomers may alter the incidence of cancer.
We found no published reports that examined the effects of purified CLA isomers on human cancer in vivo. Incidence of rat mammary tumors induced by methylnitrosourea was decreased by c9, t11-CLA in all studies and by t10, c12-CLA in just a few that included it. Those 2 isomers decreased the incidence of forestomach tumors induced by benzo (a) pyrene in mice. Both isomers reduced breast and forestomach tumorigenesis.
The c9, t11-CLA isomer did not affect the development of spontaneous tumors of the intestine or mammary gland, whereas t10, c12-CLA increased development of genetically induced mammary and intestinal tumors. In vitro, t10, c12-CLA inhibited the growth of mammary, colon, colorectal, gastric, prostate, and hepatoma cell lines. These 2 CLA isomers may regulate tumor growth through different mechanisms, because they have markedly different effects on lipid metabolism and regulation of oncogenes. In addition, c9, t11-CLA inhibited the cyclooxygenase-2 pathway and t10, c12-CLA inhibited the lipooxygenase pathway.
The t10, c12-CLA isomer induced the expression of apoptotic genes, whereas c9, t11-CLA did not increase apoptosis in most of the studies that assessed it. Several minor isomers including t9, t11-CLA; c11, t13-CLA; c9, c11-CLA; and t7, c11-CLA were more effective than c9, t11-CLA or t10, c12-CLA in inhibiting cell growth in vitro. Additional studies with purified isomers are needed to establish the health benefit and risk ratios of each isomer in humans.
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