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1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Conjugated linoleic acid evokes de-lipidation through the regulation of genes controlling lipid metabolism in adipose and liver tissue. Dietary conjugated linoleic acid increases endurance capacity and fat oxidation in mice during exercise Role of the conjugated linoleic acid in the prevention of cancer Conjugated linoleic acid suppresses the secretion of atherogenic lipoproteins from human HepG2 liver cells Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans Trans-10,cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated proteins: role of mTOR and ERK signaling Interaction of fish oil and conjugated linoleic acid in affecting hepatic activity of lipogenic enzymes and gene expression in liver and adipose tissue Isomers of conjugated linoleic acid decrease plasma lipids and stimulate adipose tissue lipogenesis without changing adipose weight in post-prandial adult sedentary or trained Wistar rat Prolonged feeding of mice with conjugated linoleic acid increases hepatic fatty acid synthesis relative to oxidation Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans Conjugated linoleic acid improves insulin sensitivity in young, sedentary humans Influence of conjugated linoleic acid on body composition and target gene expression in peroxisome proliferator-activated receptor alpha-null mice Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity Efficacy and safety of dietary supplements containing conjugated linoleic acid (CLA) for the treatment of obesity-evidence from animal and human studies Dietary conjugated linoleic acid in health: physiological effects and mechanisms of action. Conjugated linoleic acid (CLA), body fat, and apoptosis Obes Rev. 2005 Aug;6(3):247-58. Related Articles, Links Conjugated linoleic acid evokes de-lipidation through the regulation of genes controlling lipid metabolism in adipose and liver tissue. House RL, Cassady JP, Eisen EJ, McIntosh MK, Odle J. Department of Animal Science & Functional Genomics Program, North Carolina State University, Raleigh, NC 27695, USA. Conjugated linoleic acid (CLA) is a unique lipid that elicits dramatic reductions in adiposity in several animal models when included at < or = 1% of the diet. Despite a flurry of investigations, the precise mechanisms by which conjugated linoleic acid elicits its dramatic effects in adipose tissue and liver are still largely unknown. In vivo and in vitro analyses of physiological modifications imparted by conjugated linoleic acid on protein and gene expression suggest that conjugated linoleic acid exerts its de-lipidating effects by modulating energy expenditure, apoptosis, fatty acid oxidation, lipolysis, stromal vascular cell differentiation and lipogenesis. The purpose of this review shall be to examine the recent advances and insights into conjugated linoleic acid's effects on obesity and lipid metabolism, specifically focused on changes in gene expression and physiology of liver and adipose tissue. PMID: 16045640 [PubMed - in process] Lipids. 2005 Mar;40(3):265-71. Related Articles, Links Dietary conjugated linoleic acid increases endurance capacity and fat oxidation in mice during exercise. Mizunoya W, Haramizu S, Shibakusa T, Okabe Y, Fushiki T. Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. Ingestion of CLA activates beta-oxidation and causes loss of body fat in rodents. We investigated the effects of dietary CLA on endurance capacity and energy metabolism during exercise in mice. Five-week-old male BALB/c mice were fed a control diet containing 1.0% linoleic acid or a diet containing 0.5% CLA that replaced an equivalent amount of linoleic acid for 1 wk. The maximum swimming time until fatigue was significantly higher in the CLA-fed group than in the control group. During treadmill running, the respiratory exchange ratio was significantly lower in the CLA-fed group, but oxygen consumption did not differ significantly between groups, suggesting that FA contributed more as an energy substrate in the CLA-fed mice. The muscle lipoprotein lipase activity was significantly higher in the CLA-fed group than in the control group. These results suggest that CLA ingestion increases endurance exercise capacity by promoting fat oxidation during exercise. PMID: 15957252 [PubMed - in process] Crit Rev Food Sci Nutr. 2005;45(2):135-44. Related Articles, Links Role of the conjugated linoleic acid in the prevention of cancer. Lee KW, Lee HJ, Cho HY, Kim YJ. Department of Food Science and Technology, School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea. There are multiple lines of evidence that a variety of natural fatty acids are effective in health promotion. Among these fatty acids, conjugated linoleic acid (CLA)--a collective term referring to a mixture of positional and geometric isomers of linoleic acid (LA, cis-9, cis-12-octadecadienoic acid)--is currently under intensive investigation due to its health-promotion potential. The antitumor activity of CLA is of special interest, since it shows inhibitory effects against multistage carcinogenesis at relatively low dietary levels. Many studies using in vivo and in vitro models have shown that CLA suppresses the development of multistage carcinogenesis at different sites. The research to date on CLA has provided a vast amount of information about the mechanism on how CLA functions in the prevention of cancer. This article discusses characteristics of CLA in the prevention of cancer in both in vivo and in vitro studies and the possible underlying chemoprevention mechanisms. PMID: 15941017 [PubMed - in process] Clin Chem Lab Med. 2005;43(3):269-74. Related Articles, Links Conjugated linoleic acid suppresses the secretion of atherogenic lipoproteins from human HepG2 liver cells. Pal S, Takechi R, Ho SS. Department of Nutrition, Dietetics and Food Science, Curtin University of Technology, Perth, Western Australia, Australia. [email protected] 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. J Nutr. 2005 Apr;135(4):778-84. Related Articles, Links Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans. Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O. Scandinavian Clinical Research AS, NO-2027 Kjeller, Norway. [email protected] After 12 mo in a randomized, double-blind, placebo-controlled trial of conjugated linoleic acid (CLA) supplementation (2 groups received CLA as part of a triglyceride or as the free fatty acid, and 1 group received olive oil as placebo), 134 of the 157 participants who concluded the study were included in an open study for another 12 mo. The goals of the extension study were to evaluate the safety [with clinical chemistry analyses and reported adverse events (AEs)] and assess the effects of CLA on body composition [body fat mass (BFM), lean body mass (LBM), bone mineral mass (BMM)], body weight, and BMI. All subjects were supplemented with 3.4g CLA/d in the triglyceride form. Circulating lipoprotein(a) and thrombocytes increased in all groups. There was no change in fasting blood glucose. Aspartate amino transferase, but not alanine amino transferase, increased significantly. Plasma total cholesterol and LDL cholesterol were reduced, whereas HDL cholesterol and triglycerides were unchanged. The AE rate decreased compared with the first 12 mo of the study. Body weight and BFM were reduced in the subjects administered the placebo during the initial 12 mo study (-1.6 +/- 3.2 and -1.7 +/- 2.8 kg, respectively). No fat or body weight changes occurred in the 2 groups given CLA during the initial 12 mo. LBM and BMM were not affected in any of the groups. Changes in body composition were not related to diet and/or training. In conclusion, this study shows that CLA supplementation for 24 mo in healthy, overweight adults was well tolerated. It confirms also that CLA decreases BFM in overweight humans, and may help maintain initial reductions in BFM and weight in the long term. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 15795434 [PubMed - indexed for MEDLINE] J Lipid Res. 2005 May;46(5):885-95. Epub 2005 Feb 16. Related Articles, Links Trans-10,cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated proteins: role of mTOR and ERK signaling. Chung S, Brown JM, Sandberg MB, McIntosh M. Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 274026170, USA. Lipid droplet-associated proteins play an important role in adipocyte triglyceride (TG) metabolism. Here, we show that trans-10,cis-12 conjugated linoleic acid (CLA), but not cis9,trans-11 CLA, increased lipolysis and altered human adipocyte lipid droplet morphology. Before this change in morphology, there was a rapid trans-10,cis-12 CLA-induced increase in the accumulation of perilipin A in the cytosol, followed by the disappearance of perilipin A protein. In contrast, protein levels of adipose differentiation-related protein (ADRP) were increased in cultures treated with trans-10,cis-12 CLA. Immunostaining revealed that ADRP localized to the surface of small lipid droplets, displacing perilipin. Intriguingly, trans-10,cis-12 CLA increased ADRP protein expression to a much greater extent than ADRP mRNA without affecting stability, suggesting translational control of ADRP. To this end, we found that trans-10,cis-12 CLA increased activation of the mammalian target of rapamycin/p70 S6 ribosomal protein kinase/S6 ribosomal protein (mTOR/p70S6K/S6) pathway. Collectively, these data demonstrate that the trans-10,cis-12 CLA-mediated reduction of human adipocyte TG content is associated with the differential localization and expression of lipid droplet-associated proteins. This process involves both the translational control of ADRP through the activation of mTOR/p70S6K/S6 signaling and transcriptional control of perilipin A. PMID: 15716587 [PubMed - in process] Diabetes. 2005 Feb;54(2):412-23. Related Articles, Links Interaction of fish oil and conjugated linoleic acid in affecting hepatic activity of lipogenic enzymes and gene expression in liver and adipose tissue. Ide T. Laboratory of Nutritional Biochemistry, National Food Research Institute, 2-1-12 Kannondai, Tsukuba Science City 305-8642, Japan. [email protected] The interaction of dietary fish oil and conjugated linoleic acid (CLA) in affecting the activity of hepatic lipogenic enzymes and gene expression in liver and adipose tissue was examined in mice. A diet containing 1.0% CLA, mainly composed of 9cis,11trans- and 10trans,12cis- octadecadienoic acids at equivalent amounts, greatly decreased adipose tissue weight and serum concentrations of leptin and adiponectin and was accompanied by a downregulation of the expression of various adipocyte-abundant genes in epididymal adipose tissue. However, CLA increased the serum insulin concentration fourfold, and it caused hepatomegaly, with huge increases in the triacylglycerol level and the activity and mRNA levels of hepatic lipogenic enzymes. Different amounts (1.5, 3, and 6%) of fish oil added to CLA-containing diets dosedependently downregulated parameters of lipogenesis and were accompanied by a parallel decrease in the triacylglycerol level in the liver. The supplementation of CLA-containing diets with fish oil was also associated with an increase in fat pad mass and mRNA levels of many adipocyte-abundant genes in epididymal adipose tissue along with a normalization of serum concentrations of leptin and adiponectin in a dose-dependent manner. However, in mice fed a diet containing 1.5% fish oil and CLA in whom fat pad mass was still low and comparable to that in the animals fed CLA alone, the serum insulin concentration greatly exceeded (twofold) the value observed in mice fed CLA alone, indicating an aggravation of insulin resistance. This hyperinsulinemia was ameliorated with increasing amounts of fish oil in the diets. Apparently, many of the physiological effects of CLA can be reversed by fish oil. PMID: 15677499 [PubMed - indexed for MEDLINE] J Nutr Biochem. 2004 Dec;15(12):741-8. Related Articles, Links Isomers of conjugated linoleic acid decrease plasma lipids and stimulate adipose tissue lipogenesis without changing adipose weight in post-prandial adult sedentary or trained Wistar rat. Faulconnier Y, Arnal MA, Patureau Mirand P, Chardigny JM, Chilliard Y. Herbivore Research Unit, Adipose Tissue and Milk Lipids Group, National Institute for Agricultural Research-Theix, 63122 Saint-Genes Champanelle, France. The respective effects and interactions of supplementation with two conjugated linoleic acid (CLA) isomers and exercise on plasma metabolic profile, activity of lipogenic enzymes and cellularity in two adipose tissue sites, those of the liver and heart, were examined in adult Wistar rats. Rats that were either sedentary or exercise-trained by treadmill running were fed one of four diets: a diet without CLA; a diet with either 1% cis 9, trans 11 CLA or 1% trans 10, cis 12 CLA; or a mixture of both isomers (1% of each) for 6 weeks. We observed that the exercise decreased lipogenic enzyme activities in epididymal and perirenal adipose tissue. Plasma cholesterol, insulin, and leptin concentrations were lower in exercise-trained rats than in sedentary rats. The ingestion of either CLA mixture or the trans 10, cis 12 CLA increased lipogenic enzyme activities in epididymal tissue and more markedly in perirenal adipose tissue, especially in sedentary rats, and without affecting adipose tissue weight or cellularity. A similar effect of trans 10, cis 12 CLA was observed in regard to malic enzyme activity in the liver. In addition, this isomer decreased plasma lipid and urea concentrations and increased plasma 3-hydroxybutyrate levels. The ingestion of cis 9, trans 11 CLA increased fatty acid synthase activity in perirenal adipose tissue in sedentary rats and decreased plasma cholesterol and leptin concentrations. These results show that isomers of CLA decrease plasma lipids and stimulate adipose tissue lipogenesis without changing adipose weight in adult sedentary or exercise-trained rat, thus suggesting a stimulation of adipose tissue turnover. PMID: 15607647 [PubMed - indexed for MEDLINE] J Nutr Biochem. 2004 Nov;15(11):680-7. Related Articles, Links Prolonged feeding of mice with conjugated linoleic acid increases hepatic fatty acid synthesis relative to oxidation. Javadi M, Beynen AC, Hovenier R, Lankhorst A, Lemmens AG, Terpstra AH, Geelen MJ. Department of Nutrition, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 16, P.O. Box 80.152, 3508 TD Utrecht, The Netherlands. Feeding mice conjugated linoleic acid (9 cis,11 trans/9 trans,11 cis-and 10 trans,12 cis-CLA in equal amounts) resulted in triacylglycerol accumulation in the liver. The objective of this study was to examine whether this steatosis is associated with changes in hepatic fatty acid synthesis and oxidation. Therefore, we measured the activities of key enzymes of fatty acid synthesis, i.e., acetyl-CoA carboxylase and fatty acid synthase and of fatty acid oxidation, i.e., 3-hydroxy-acylCoA dehydrogenase and citrate synthase in livers of mice fed a diet with 0.5% (w/w) CLA. CLA (a 1:1 mixture of the 10 trans, 12 cis and 9 cis, 11 trans isomers of octadecadenoic acid) was administered for 3 and 12 weeks with high-oleic sunflower oil fed as control. The proportion of body fat was significantly lower on the CLA than on the control diet and this effect was already significant after 3 weeks. The specific activites of 3-hydroxy-acyl-CoA dehydrogenase and citrate synthase were unaffected by CLA both after 3 and 12 weeks. The specific activity of fatty acid synthase was nonsignificantly raised (by 12%) after 3 weeks on the CLA diet but had increased significantly (by 34%) after 12 weeks of feeding. The specific activity of acetyl-CoA carboxylase had also increased both after 3 weeks (by 53%) and 12 weeks (by 23%) on the CLA diet, but this effect did not reach statistical significance. Due to CLA-induced hepatomegaly, the overall capacity for both fatty acid oxidation and synthesis-as evidenced by the total hepatic activities of 3-hydroxy-acyl-CoA dehydrogenase, citrate synthase, acetyl-CoA carboxylase, and fatty acid synthase-was significantly greater in the CLA-fed group after 12 weeks, although the overall capacity for fatty acid synthesis had increased more than that for fatty acid oxidation. Thus, this study indicates that prolonged, but not short-term, feeding mice with CLA increased hepatic fatty acid synthesis relative to oxidation, despite the decrease in body fat and the increase in liver weight seen earlier. It is concluded that the observed CLA-induced changes in hepatic fatty acid synthesis and oxidation are the result, rather than the cause, of the lowering of body fat. PMID: 15590272 [PubMed - indexed for MEDLINE] Am J Clin Nutr. 2004 Jun;79(6):1118-25. Related Articles, Links Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O. Scandinavian Clinical Research AS, Kjeller, Norway. [email protected] BACKGROUND: Short-term trials showed that conjugated linoleic acid (CLA) may reduce body fat mass (BFM) and increase lean body mass (LBM), but the long-term effect of CLA was not examined. OBJECTIVE: The objective of the study was to ascertain the 1-y effect of CLA on body composition and safety in healthy overweight adults consuming an ad libitum diet. DESIGN: Male and female volunteers (n = 180) with body mass indexes (in kg/m(2)) of 25-30 were included in a double-blind, placebo-controlled study. Subjects were randomly assigned to 3 groups: CLA-free fatty acid (FFA), CLA-triacylglycerol, or placebo (olive oil). Change in BFM, as measured by dual-energy X-ray absorptiometry, was the primary outcome. Secondary outcomes included the effects of CLA on LBM, adverse events, and safety variables. RESULTS: Mean (+/SD) BFM in the CLA-triacylglycerol and CLA-FFA groups was 8.7 +/- 9.1% and 6.9 +/- 9.1%, respectively, lower than that in the placebo group (P < 0.001). Subjects receiving CLA-FFA had 1.8 +/- 4.3% greater LBM than did subjects receiving placebo (P = 0.002). These changes were not associated with diet or exercise. LDL increased in the CLA-FFA group (P = 0.008), HDL decreased in the CLA-triacylglycerol group (P = 0.003), and lipoprotein(a) increased in both CLA groups (P < 0.001) compared with month 0. Fasting blood glucose concentrations remained unchanged in all 3 groups. Glycated hemoglobin rose in all groups from month 0 concentrations, but there was no significant difference between groups. Adverse events did not differ significantly between groups. CONCLUSION: Long-term supplementation with CLA-FFA or CLAtriacylglycerol reduces BFM in healthy overweight adults. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 15159244 [PubMed - indexed for MEDLINE] Med Sci Sports Exerc. 2004 May;36(5):814-20. Related Articles, Links Conjugated linoleic acid improves insulin sensitivity in young, sedentary humans. Eyjolfson V, Spriet LL, Dyck DJ. Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada. BACKGROUND: Preliminary evidence in obese diabetic rats suggests that conjugated linoleic acid (CLA) may have antidiabetic properties, based on reductions in fasting glucose and insulin concentrations. However, in lean rats, CLA causes hyperinsulinemia. Furthermore, experiments in humans also suggest that CLA may worsen insulin sensitivity. OBJECTIVES: The present study examined whether CLA supplementation can improve insulin sensitivity in humans. DESIGN:: Sixteen young sedentary individuals (age, 21.5 +/- 0.4 yr (mean +/- SEM); body mass, 77.6 +/- 3.4 kg) participated in this study. Ten subjects received 4 g x d of mixed CLA isomers (35.5%cis-9, trans-11; 36.8%trans-10, cis-12) for 8 wk, whereas six subjects received placebo (safflower oil). Oral glucose tolerance tests were performed at baseline (0), 4 and 8 wk of supplementation. RESULTS:: After 8 wk of CLA supplementation, insulin sensitivity index (ISI) increased (14.4 +/- 1.0, 8 wk vs 11.3 +/- 1.3, 0 wk; P < 0.05), which corresponded to a decrease in fasting insulin concentrations. Six of the 10 subjects showed large increases in their ISI (range, +27 to 90%), whereas two demonstrated essential no change (+3 to 5%), and two had a decrease in insulin sensitivity (-12 to -13%). ISI was unchanged over 8 wk in the placebo group. CONCLUSIONS: Our results indicate that a common dosage of a commercially available CLA supplement can improve ISI in young, sedentary individuals. However, there is considerable individual variability in the response. Additional studies are required to identify underlying metabolic changes in human skeletal muscle. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 15126715 [PubMed - indexed for MEDLINE] Biochim Biophys Acta. 2001 Oct 31;1533(3):233-42. Related Articles, Links Influence of conjugated linoleic acid on body composition and target gene expression in peroxisome proliferator-activated receptor alphanull mice. Peters JM, Park Y, Gonzalez FJ, Pariza MW. Department of Veterinary Science and Center for Molecular Toxicology, Pennsylvania State University, University Park, PA 16802, USA. [email protected] The mechanisms underlying the beneficial effects of conjugated linoleic acid (CLA) are unknown, but one hypothesis is that they are mediated by the nuclear receptor, peroxisome proliferatoractivated receptor (PPARalpha). In this work, the effect of dietary CLA on body weight gain, body composition, serum lipids and tissue specific PPAR target gene expression was examined in PPARalpha-null mice. Male wild-type or PPARalpha-null mice were fed either a control diet or one containing 0.5% CLA for a period of 4 weeks. Weight gain in wild-type and PPARalpha-null mice fed CLA was similar, and significantly less than controls. Whole body fat content was lower in wild-type and PPARalpha-null mice while whole body protein content was increased in both genotypes fed CLA compared to controls. Serum triglycerides were lowered in both genotypes as a result of dietary CLA. While CLA feeding resulted in specific activation of PPARalpha in liver, alterations in liver, adipose and muscle mRNAs were also found that were independent of PPARalpha genotype including those encoding uncoupling proteins (UCPs), mitochondrial fatty acid oxidizing enzymes, and fatty acid transporter. These results demonstrate that despite specific activation of PPARalpha-dependent gene expression, the influence of CLA on body composition appears to be independent of PPARalpha. Further, CLA causes increased levels of mRNAs encoding lipid metabolizing and mitochondrial uncoupling proteins that likely contribute to the mechanisms underlying reduced fat/increased lean body mass resulting from consumption of dietary CLA. PMID: 11731333 [PubMed - indexed for MEDLINE] J Biol Chem. 2004 Jun 18;279(25):26735-47. Epub 2004 Apr 2. Related Articles, Links Conjugated linoleic acid induces human adipocyte delipidation: autocrine/paracrine regulation of MEK/ERK signaling by adipocytokines. Brown JM, Boysen MS, Chung S, Fabiyi O, Morrison RF, Mandrup S, McIntosh MK. Department of Nutrition, University of North Carolina at Greensboro, Greensboro, North Carolina 27402-6170, USA. Dietary conjugated linoleic acid (CLA) reduces body fat in animals and some humans. Here we show that trans-10, cis-12 CLA, but not cis-9, trans-11 CLA, when added to cultures of stromal vascular cells containing newly differentiated human adipocytes, caused a time-dependent decrease in triglyceride content, insulin-stimulated glucose and fatty acid uptake, incorporation into lipid, and oxidation compared with controls. In parallel, gene expression of peroxisome proliferator-activated receptor-gamma and many of its downstream targets were diminished by trans-10, cis-12 CLA, whereas leptin gene expression was increased. Prior to changes in gene expression and metabolism, trans-10, cis-12 CLA caused a robust and sustained activation of mitogen-activated protein kinase kinase/extracellular signal-related kinase (MEK/ERK) signaling. Furthermore, the trans-10, cis-12 CLA-mediated activation of MEK/ERK could be attenuated by pretreatment with U0126 and pertussis toxin. In parallel, pretreatment with U0126 blocked the ability of trans-10, cis-12 CLA to alter gene expression and attenuate glucose and fatty acid uptake of the cultures. Intriguingly, the induction by CLA of MEK/ERK signaling was linked to hypersecretion of adipocytokines interleukin-6 and interleukin-8. Collectively, these data demonstrate for the first time that trans-10, cis-12 CLA decreases the triglyceride content of newly differentiated human adipocytes by inducing MEK/ERK signaling through the autocrine/paracrine actions of interleukins-6 and 8. PMID: 15067015 [PubMed - indexed for MEDLINE] J Nutr. 2003 Oct;133(10):3041-6. Related Articles, Links Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity. Brown JM, McIntosh MK. Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 274026170, USA. 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, trans11 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. Publication Types: Review Review, Tutorial PMID: 14519781 [PubMed - indexed for MEDLINE] J Lipid Res. 2003 Dec;44(12):2234-41. Epub 2003 Aug 16. Related Articles, Links Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. Larsen TM, Toubro S, Astrup A. Department of Human Nutrition, Center for Advanced Food Studies, The Royal Veterinary and Agricultural University, DK-1958 Frederiksberg C, Denmark. [email protected] Dietary supplements containing conjugated linoleic acid (CLA) are widely promoted as weight loss agents available over the counter and via the Internet. In this review, we evaluate the efficacy and safety of CLA supplementation based on peer-reviewed published results from randomized, placebo-controlled, human intervention trials lasting more than 4 weeks. We also review findings from experimental studies in animals and studies performed in vitro. CLA appears to produce loss of fat mass and increase of lean tissue mass in rodents, but the results from 13 randomized, controlled, short-term (<6 months) trials in humans find little evidence to support that CLA reduces body weight or promotes repartitioning of body fat and fat-free mass in man. However, there is increasing evidence from mice and human studies that the CLA isomer trans-10, cis-12 may produce liver hypertrophy and insulin resistance via a redistribution of fat deposition that resembles lipodystrophy. CLA also decreases the fat content of both human and bovine milk. In conclusion, although CLA appears to attenuate increases in body weight and body fat in several animal models, CLA isomers sold as dietary supplements are not effective as weight loss agents in humans and may actually have adverse effects on human health. Publication Types: Review Review, Tutorial PMID: 12923219 [PubMed - indexed for MEDLINE]