Conjugated linoleic acids: are they beneficial or detrimental to health?

Conjugated linoleic acids (CLAs) comprise a family of positional and geometric isomers of linoleic acid (18:2n − 6; LA) that are formed by biohydrogenation and oxidation processes in nature. The major dietary sources of these unusual fatty acids are foods derived from ruminant animals, in particular dairy products. The main form of CLA, cis-9, trans-11-18:2, can be produced directly by bacterial hydrogenation in the rumen or by delta-9 desaturation of the co-product vaccenic acid (trans-11-18:1) in most mammalian tissues including man. The second most abundant isomer of CLA is the trans-10, cis-12-18:2 form. Initially identified in grilled beef as a potential anti-carcinogen a surprising number of health benefits have subsequently been attributed to CLA mixtures and more recently to the main individual isoforms. It is also clear from recent studies that the two main isoforms can have different effects on metabolism and cell functions and can act through different cell signalling pathways. The majority of studies on body compositional effects (i.e. fat loss, lean gain), on cancer and cardiovascular disease attenuation, on insulin sensitivity and diabetes and on immune function have been conducted with a variety of animal models. Observations clearly emphasise that differences exist between mammalian species in their response to CLAs with mice being the most sensitive. Recent studies indicate that some but not all of the effects observed in animals also pertain to human volunteers. Reports of detrimental effects of CLA intake appear to be largely in mice and due mainly to the trans-10, cis-12 isomer. Suggestions of possible deleterious effects in man due to an increase in oxidative lipid products (isoprostanes) with trans-10, cis-12 CLA ingestion require substantiation. Unresponsiveness to antioxidants of these non-enzymatic oxidation products casts some doubt on their physiological relevance. Recent reports, albeit in the minority, that CLAs, particularly the trans-10, cis-12 isomer, can elicit pro-carcinogenic effects in animal models of colon and prostate cancer and can increase prostaglandin production in cells also warrant further investigation and critical evaluation in relation to the many published anti-cancer and anti-prostaglandin effects of CLAs.     

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

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.     

Influence of different CLA isomers on insulin resistance and adipocytokines in pre-diabetic, middle-aged men with PPARγ2 Pro12Ala polymorphism

Conjugated linoleic acids (CLAs) are natural PPARγ ligands, which showed conflicting effects on metabolism in humans. We examined metabolic effects of different isomers of CLA in subjects with PPARγ2 Pro12Ala polymorphisms. A total of 35 men underwent four intervention periods in a crossover study design: subjects with either genotypes received c9, t11 CLA or t10, c12 CLA, a commercially available 1:1 mix of both isomers or reference oil (linoleic acid (LA)). Adipocytokines, insulin, glucose and triglycerides were assessed in the fasting state and after a standardized mixed meal. Across all genotypes, there was a significant (p = 0.025) CLA treatment effect upon postprandial (pp) HOMA-IR values, with c9, t11 CLA and CLA isomer mix improving, but t10, c12 CLA isomer worsening. In Ala12Ala subjects, the t10, c12 isomer caused weight gain (p = 0.03) and tended to increase postprandial insulin levels (p = 0.05). In Pro12Pro subjects, t10, c12 resulted in reduction in waist circumference (p = 0.03). The comparison of the different genotype groups revealed statistically different changes in fasting and postprandial insulin, HOMA-IR and leptin after intervention. c9, t11 CLA and the commercial CLA mix showed beneficial effects on insulin sensitivity compared with LA, while t10, c12 CLA adversely affects body weight and insulin sensitivity in different PPAR genotypes. CLA isomers have different effects on metabolism in Ala and Pro carriers.     

植物乳杆菌ZS2058在磷酸盐缓冲液体系中生物转化共轭亚油酸

植物乳杆菌ZS2058是从泡菜中筛选到一株具有转化共轭亚油酸能力的乳酸菌。该菌株在MRS培养基中经0.5mg/mL的亚油酸诱导培养后,所获得的菌体细胞具有较强的转化能力。文中就植物乳杆菌ZS2058水洗细胞在磷酸盐缓冲液体系中生物转化共轭亚油酸进行了深入研究。在非厌氧条件下,植物乳杆菌ZS2058在亚油酸浓度为1mg/mL,湿细胞质量浓度约为150mg/mL,120r/min、37℃的条件下反应24h后,能将亚油酸转化为共轭亚油酸和羟基脂肪酸,其中c9,t11-CLA占所产生的CLA总量的96.4%,产量可高达312.4μg/mL,说明该菌株有很强的专一性。随着反应进一步进行,反应至36h时,c9,t11-CLA含量逐渐减少,伴随着大量羟基脂肪酸的产生;并且,以CLA(c9,t11-CLA和t10,c12-CLA的混合样品)为底物进行反应时,c9,t11-CLA被转化为羟基脂肪酸。由此可知,c9,t11-CLA可能是该菌株生物转化LA过程中的一个中间产物。     

t10,c12 Conjugated linoleic acid induces compensatory growth after immune challenge

Previous work demonstrated that feeding commercial preparations of conjugated linoleic acid (CLA) [a 50:50 mixture of c9,t11 and t10,c12 CLA (cCLA)] partially overcame lipopolysaccharide (LPS)-induced growth depression. The objective of this study was to determine which CLA isomer was responsible for the reduction of LPS-induced growth depression. Dietary cCLA supplementation for 3 weeks protected mice from LPS-induced weight loss 24 h after injection compared to mice fed isocaloric and isonitrogenous control diets supplemented with either corn oil (CO) or a mixture of CO and olive oil. Dietary c9,t11 or t10,c12 CLA led to body weight loss intermediate to controls and cCLA. After LPS-induced weight loss, the t10,c12 CLA fed mice regained weight faster than the control or c9,t11 CLA fed mice. Dietary t10,c12 CLA and cCLA reduced plasma tumor necrosis factor 2 h after LPS stimulation. While neither c9,t11 nor t10,c12 CLA isomers alone protected from immune-induced weight loss, the t10,c12 CLA isomer induced compensatory gain.     

t10c12-CLA maintains higher bone mineral density during aging by modulating osteoclastogenesis and bone marrow adiposity

Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism. Earlier, we showed that CLA (equal mixture of c9t11-CLA and t10c12-CLA) could protect age-associated bone loss by modulating inflammatory markers and osteoclastogenesis. Since, c9t11-CLA and t10c12-CLA isomers differentially regulate functional parameters and gene expression in different cell types, we examined the efficacy of individual CLA isomers against age-associated bone loss using 12 months old C57BL/6 female mice fed for 6 months with 10% corn oil (CO), 9.5% CO + 0.5% c9t11-CLA, 9.5% CO + 0.5% t10c12-CLA or 9.5% CO + 0.25% c9t11-CLA + 0.25% t10c12-CLA. Mice fed a t10c12-CLA diet maintained a significantly higher bone mineral density (BMD) in femoral, tibial and lumbar regions than those fed CO and c9t11-CLA diets as measured by dual-energy-X-ray absorptiometry (DXA). The increased BMD was accompanied by a decreased production of osteoclastogenic factors, that is, RANKL, TRAP5b, TNF-alpha and IL-6 in serum. Moreover, a significant reduction of high fat diet-induced bone marrow adiposity was observed in t10c12-CLA fed mice as compared to that of CO and c9t11-CLA fed mice, as measured by Oil-Red-O staining of bone marrow sections. In addition, a significant reduction of osteoclast differentiation and bone resorbing pit formation was observed in t10c12-CLA treated RAW 264.7 cell culture stimulated with RANKL as compared to that of c9t11-CLA and linoleic acid treated cultures. In conclusion, these findings suggest that t10c12-CLA is the most potent CLA isomer and it exerts its anti-osteoporotic effect by modulating osteoclastogenesis and bone marrow adiposity.     

Effect of monensin, fish oil or their combination on in vitro fermentation and conjugated linoleic acid (CLA) production by ruminal bacteria

An in vitro study was conducted to examine the effect of adding monensin, fish oil, or their combination on rumen fermentation and conjugated linoleic acid (CLA) production by mixed ruminal bacteria when incubated with safflower oil. Concentrate (1 g/100 ml) with safflower oil (0.2 g/100 ml) was added to a mixed solution (600 ml) of strained rumen fluid and buffer (control). Monensin (10 ppm), fish oil (0.02 g/100 ml), or monensin plus fish oil was also added into control mixture. All the culture solutions prepared were incubated anaerobically at 39 °C for 12 h. A higher pH and ammonia concentration were observed from the culture solution containing monensin at 12 h of incubation than those from the control or the culture containing fish oil. Monensin increased (P < 0.007) the C₃ content over all the collection times of culture solution while reducing the C₄ content at 6 h (P < 0.018) and 12 h (P < 0.001) of incubations. Supplementation of monensin, fish oil or their combination changed the content of C₁₈-fatty acids of ruminal culture. Monensin alone reduced (P < 0.021) the content of cis-9, trans-11 CLA compared to fish oil at all sampling times, but increased (P < 0.041) the trans-10, cis-12 CLA production compared to fish oil addition and the control which were similar at incubation for 12 h. The combination of monensin and fish oil increased the content of cis-9, trans-11 CLA (P < 0.023) and transvaccenic acid (TVA, P < 0.018) significantly compared to the control or monensin alone at incubation for 12 h.     

Potent inhibitory effect of trans9, trans11 isomer of conjugated linoleic acid on the growth of human colon cancer cells

This study compared the growth inhibitory effects of pure conjugated linoleic acid (CLA) isomers [cis(c)9,c11-CLA, c9,trans(t)11-CLA, t9,t11-CLA, and t10,c12-CLA] on human colon cancer cell lines (Caco-2, HT-29 and DLD-1). When Caco-2 cells were incubated up to 72 h with 200 μM, each isomer, even in the presence of 10% fetal bovine serum (FBS), cell proliferation was inhibited by all CLA isomers in a time-dependent manner. The strongest inhibitory effect was shown by t9,t11-CLA, followed by t10,c12-CLA, c9,c11-CLA and c9,t11-CLA, respectively. The strongest effect of t9,t11-CLA was also observed in other colon cancer cell lines (HT-29 and DLD-1). The order of the inhibitory effect of CLA isomer was confirmed in the presence of 1% FBS. CLA isomers supplemented in the culture medium were readily incorporated into the cellular lipids of Caco-2 and changed their fatty acid composition. The CLA contents in cellular lipids were 26.2±2.7% for t9,t11-CLA, 35.9±0.3% for c9,t11-CLA and 46.3±0.8% for t10,c12-CLA, respectively. DNA fragmentation was clearly recognized in Caco-2 cells treated with t9,t11-CLA. This apoptotic effect of t9,t11-CLA was dose- and time-dependent. DNA fragmentation was also induced by 9c,11t-CLA and t10,c12-CLA. However, fragmentation levels with both isomers were much lower than that with t9,t11-CLA. t9t11-CLA treatment of Caco-2 cells decreased Bcl-2 levels in association with apoptosis, whereas Bax levels remained unchanged. These results suggest that decreased expression of Bcl-2 by t9t11-CLA might increase the sensitivity of cells to lipid peroxidation and to programmed cell death, apoptosis.     

Effects of conjugated linoleic acid on body fat accumulation and serum lipids in hamsters fed an atherogenic diet

Conjugated linoleic acid (CLA) refers to a mixture of naturally occurring positional and geometric isomers of linoleic acid that exist in dairy products and meat. The aim of the present work was to study the effects of c-9,t-11 and t-10,c-12 CLA isomers on body fat accumulation and serum lipids in hamsters fed an atherogenic diet. Hamsters were divided in four groups: one group was fed a chow diet (control) and the other three groups were given semi-purified atherogenic diets with 0.5% linoleic acid (LA), c-9,t-11 or t-10,c-12 CLA. Body weight and food intake were measured daily. After 6 weeks, adipose tissues from different anatomical locations and liver were dissected and weighed. Serum glucose, total cholesterol, HDL-c, LDL-c and triacylglycerol levels, as well as total and free cholesterol, triacylglycerol and phospholipid content in liver were determined by enzymatic methods. No differences in either energy intake or final body weight were found. The addition of t-10,c-12 CLA reduced fat accumulation and led to lower serum cholesterol, as compared with LA group. Nevertheless the level remained higher than in the control animals. The reduction in serum cholesterol was limited to LDL-c. This isomer also reduced triacylglycerol content in liver but did not modify serum triacylglycerol level. In summary, the present study demonstrates that t-10,c-12 CLA is the biologically active agent when anti-obesity and hypocholesterolaemic properties of CLA are considered. In contrast, the isomer c-9,t-11 has no effect on lipid metabolism in hamsters.     

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.     

反刍动物体内共轭亚油酸生物合成途径研究进展

共轭亚油酸是一组共轭双键具有不同位置和几何构象的亚油酸异构体,主要存在于反刍动物的肉及乳中。本文就其中2种具有重要生理功能的共轭亚油酸(c-9,t-11CLA和t-10,c-12CLA)的生物合成途径的研究进行综述,以期了解共轭亚油酸代谢途径及其调控路径,为今后利用合成生物学指导共轭亚油酸的合成奠定基础。     

Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse

Conjugated linoleic acids (CLA) are a class of positional, geometric, conjugated dienoic isomers of linoleic acid (LA). Dietary CLA supplementation results in a dramatic decrease in body fat mass in mice, but also causes considerable liver steatosis. However, little is known of the molecular mechanisms leading to hepatomegaly. Although c9,t11- and t10,c12-CLA isomers are found in similar proportions in commercial preparations, the respective roles of these two molecules in liver enlargement has not been studied. We show here that mice fed a diet enriched in t10,c12-CLA (0.4% w/w) for 4 weeks developed lipoatrophy, hyperinsulinemia, and fatty liver, whereas diets enriched in c9,t11-CLA and LA had no significant effect. In the liver, dietary t10,c12-CLA triggered the ectopic production of peroxisome proliferator-activated receptor gamma (PPARgamma), adipocyte lipid-binding protein and fatty acid transporter mRNAs and induced expression of the sterol responsive element-binding protein-1a and fatty acid synthase genes. In vitro transactivation assays demonstrated that t10,c12- and c9,t11-CLA were equally efficient at activating PPARalpha, beta/delta, and gamma and inhibiting liver-X-receptor. Thus, the specific effect of t10,c12-CLA is unlikely to result from direct interaction with these nuclear receptors. Instead, t10,c12-CLA-induced hyperinsulinemia may trigger liver steatosis, by inducing both fatty acid uptake and lipogenesis.     

Conjugated linoleic acids promote human fat cell apoptosis.

Conjugated linoleic acids (CLAs) are conjugated dienoic isomers of linoleic acid. Some isomers have been shown to reduce fat mass in animal and cell culture models. However, controversial results were obtained in studies of supplementation of CLAs in human subjects. In order to get more insights into the direct effects of CLAs on human fat cells, we have studied the influence of cis-9, trans-11 CLA and trans-10, cis-12 CLA on the biology of human SGBS preadipocytes and adipocytes. Both CLA isomers equally inhibited the proliferation of preadipocytes in a dose-dependent manner. Continuous treatment with 1-10 microM trans-10, cis-12 CLA, and to a weaker extent cis-9, trans-11 CLA, inhibited accumulation of lipids during adipogenic differentiation. Treatment with higher doses of CLA induced apoptosis in preadipocytes, in differentiating cells, and adipocytes. The trans-10, cis-12 isomer had a higher apoptotic potency in adipocytes than cis-9, trans-11 CLA. Taken together, the treatment of human preadipocytes and adipocytes with physiological relevant concentrations of CLAs resulted in an impairment of proliferation and differentiation and induction of apoptosis. The trans-10, cis-12 isomer was more potent than the cis-9, trans-11 isomer. Further clinical studies are needed to evaluate the effects of CLAs on human fat mass and metabolism in vivo.     

Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARgamma modulator

A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis9, trans11 (c 9,t11) and trans10, cis12 (t10,c12) CLA. A crude mixture of these isomers has been shown in animal studies to alter body composition by a reduction in body fat mass as well as an increase in lean body mass, with the t10,c12 isomer having the most pronounced effect. The objective of this study was to establish the molecular mechanisms by which t10,c12 CLA affects lipid accumulation in adipocytes. We have shown that t10,c12 CLA prevents lipid accumulation in human and mouse adipocytes at concentrations as low as 5 microM and 25 microM, respectively. t10,c12 CLA fails to activate peroxisome proliferator-activated receptor gamma (PPARgamma) but selectively inhibits thiazolidinedione-induced PPARgamma activation in 3T3-L1 adipocytes. Treatment of mature adipocytes with t10,c12 CLA alone or in combination with Darglitazone down-regulates the mRNA expression of PPARgamma as well as its target genes, fatty acid binding protein (aP2) and liver X receptor alpha (LXRalpha). Taken together, our results suggest that the trans10, cis12 CLA isomer prevents lipid accumulation in adipocytes by acting as a PPARgamma modulator.     

Differential effects of conjugated linoleic acid isomers in insulin-resistant female C57Bl/6J mice

Obesity is associated with a high risk of developing diabetes and cardiovascular disease. Therefore, management of body weight to prevent obesity remains as an important priority. The present investigation addresses the effects of conjugated linoleic acid (CLA) isomers on body weight and composition of body fat in female C57Bl/6J mice. To investigate the differential effects of individual CLA isomers and their mixture on changes in lean mass, fat mass, glucose and insulin, 6-month-old female C57BL/6J mice were fed with 10% corn oil (CO) as a dietary fat source and either supplemented with purified cis 9,trans 11 (c9t11) CLA (0.5%) or trans 10,cis 12 (t10c12) CLA (0.5%) and/or their mixture (50:50) for 6 months. As a result of 6 months' dietary intervention, both the t10c12-CLA and CLA mix showed increased lean mass and reduced fat mass compared to the CO and c9t11-CLA groups. Insulin resistance was, however, increased in t10c12-CLA and CLA mix-fed groups based on the results of homeostasis model assessment (HOMA), the revised quantitative insulin-sensitivity check index (R-QUICKI) and also with intravenous glucose tolerance test (IVGTT). In conclusion, long-term feeding of the major CLA isomers in 12-month-old C57Bl/6J mice revealed a contrasting effect on fat mass, glucose and insulin metabolism. The t10c12 isomer is found to reduce the fat mass and increase the lean mass but significantly contributed to increase insulin resistance and liver steatosis, whereas c9t11 isomer prevented the insulin resistance.     

The 10trans,12cis isomer of conjugated linoleic acid suppresses the development of hypertension in Otsuka Long-Evans Tokushima fatty rats

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid found in beef, lamb, and dairy products. CLA has attracted considerable attention over the past several decades because of its potentially beneficial biological effects, including protective effects against several cancers, atherosclerosis, and obesity. Here we provide the first evidence that the 10trans,12cis-CLA isomer is able to suppress increases in blood pressure during the onset of obesity in OLETF rats. After 3 weeks of feeding with 10t,12c-CLA, systolic blood pressure was significantly lowered compared with rats fed linoleic acid or 9c,11t-CLA. Abdominal adipose tissue weight was also significantly lowered in rats fed 10t,12c-CLA, but not in those which were fed 9c,11t-CLA. In addition, we found that the relative mRNA expressions of angiotensinogen and leptin were suppressed by 10t,12c-CLA in adipose tissue. We speculate that the antihypertensive effect of 10t,12c-CLA can be attributed to the lowered secretion of hypertensive adipocytokines from abdominal adipose tissues.     

Antiplatelet effects of conjugated linoleic acid isomers

Conjugated diene isomers of linoleic acid (CLA) are normal constituents of certain foods and exhibit anticarcinogenic and antiatherogenic properties. In the present study, the effects of several CLA isomers on human platelet aggregation and arachidonic acid metabolism were examined. It was found that 9c,11t-CLA, 10t, 12c-CLA and 13-hydroxy-9c,11t-octadecadienoic acid (13-HODE) inhibited arachidonic acid- and collagen-induced platelet aggregation with I50s in the 5-7 microM range. The nonconjugated 9c, 12c-LA was about 300% and 50%, respectively, less potent an inhibitor with these aggregating agents. Using either thrombin or the calcium ionophore A23187 as aggregating agents, a CLA isomer mix was also found to be more inhibitory than 9c,12c-LA. The 9c,11t- and 10t,12c-CLA isomers as well as the CLA isomer mix inhibited formation of the proaggregatory cyclooxygenase-catalyzed product TXA2, as measured by decreased production of its inactive metabolite [14C]TXB2 from exogenously added [14C]arachidonic acid (I50s=9-16 microM). None of the CLA isomers tested inhibited production of the platelet lipoxygenase metabolite [14C]12-HETE. The additional presence of a hydroxyl group gave opposite results: 13-HODE (I50=3 microM) was about 4-fold more potent a cyclooxygenase inhibitor than the 9c,11t-CLA isomer but 9-HODE was 2- to 3-fold less effective an inhibitor (I50=34 microM) of [14C]TXB2 formation than the corresponding 10t,12c-CLA. In both the aggregation and arachidonic acid metabolism experiments, the inhibitory effects of CLA on platelets were reversible and dependent on the time of addition of either the aggregating agent or the [14C]arachidonic acid substrate. These studies suggest that CLA isomers may also possess antithrombotic properties.     

Different effects of conjugated linoleic acid isomers on lipoprotein lipase activity in 3T3-L1 adipocytes

Conjugated linoleic acids (CLAs) are the positional and geometric isomers of linoleic acid. In the present study the effects of cis-9, trans-11 CLA (c9,t11 CLA) and trans-10, cis-12 CLA (t10,c12 CLA ) on intracellular and heparin-releasable (HR-) lipoprotein lipase (LPL) activity in 3T3-L1 adipocytes were investigated. Cells were exposed to the two CLA isomers and linoleic acid, which were bound to bovine serum albumin (BSA). In the adipocytes insulin up-regulated and tumor necrosis factor alpha (TNFalpha) down-regulated HR-LPL activity, which corresponds with the findings in vivo. The experimental fatty acids at low concentrations (<30 μmol/L) moderately increased intracellular and HR-LPL activity. At a concentration of 100 μmol/L, c9,t11 CLA and t10,c12 CLA suppressed HR-LPL activity to 20 and 24% below the BSA control level, respectively, while linoleic acid had no effect unless its concentration was as high as 1000 μmol/L. Insulin abolished the inhibitory effect of c9,t11 CLA, but not of t10,c12 CLA. In the presence of insulin, t10,c12 CLA inhibited HR-LPL activity by 41% compared to BSA control. In contrast to TNFalpha, which suppressed both intracellular LPL and HR-LPL activity, CLAs suppressed HR-LPL activity without decreasing intracellular LPL activity. Additionally, t10,c12 CLA (100 μmol/L) partially prevented TNFalpha-induced decrease of intracellular LPL activity. These results indicate that CLAs differ from linoleic acid in regulating HR-LPL activity, and t10,c12 CLA appeared to be more effective than c9,t11 CLA.     

Hepatic retinol secretion and storage are altered by dietary CLA: common and distinct actions of CLA c9,t11 and t10,c12 isomers

Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid obtained from ruminant products. Previous studies in rats and pigs showed that a dietary equimolar mixture of c9,t11 and t10,c12 CLA isomers induces changes in serum and tissue levels of retinoids (vitamin A derivatives). However, the mechanism(s) responsible for these actions remain(s) unexplored. Given the numerous crucial biological functions regulated by retinoids, it is key to establish whether the perturbations in retinoid metabolism induced by dietary CLA mediate some of the beneficial effects associated with intake of this fatty acid or, rather, have adverse consequences on health. To address this important biological question, we began to explore the mechanisms through which dietary CLA alters retinoid metabolism. By using enriched preparations of CLA c9,t11 or CLA t10,c12, we uncoupled the effects of these two CLA isomers on retinoid metabolism. Specifically, we show that both isomers induce hepatic retinyl ester accumulation. However, only CLA t10,c12 enhances hepatic retinol secretion, resulting in increased serum levels of retinol and its specific carrier, retinol-binding protein (RBP). Dietary CLA t10,c12 also redistributes retinoids from the hepatic stores toward the adipose tissue and possibly stimulates hepatic retinoid oxidation. Using mice lacking RBP, we also demonstrate that this key protein in retinoid metabolism mediates hepatic retinol secretion and its redistribution toward fat tissue induced by CLA t10,c12 supplementation.     

Conjugated linoleic acids: all the same or to everyone its own function?

Conjugated linoleic acid (CLA) is a generic term referring to a mixture of geometrical and positional isomers of linoleic acid in which up to 16 members have been identified. Many potentially beneficial health effects have been ascribed to these fatty acids when consumed as a mixture, and where generally 2 isomers dominate, e.g. the 9c, 11t-isomer, the so-called rumenic acid, and the 10t, 12c-isomer: anti-carcinogenic, immune modulator, anti-atherosclerotic, and anti-obesity among the most spectacular. The question arises as to whether the pleiotropic biological activity is supported by one or several of the isomers. Recent studies using pure individual isomers have started to elucidate this issue, but many others are required to ascribe a respective role to each CLA isomer (the main ones as well as the minor ones), such as those occurring in some complex mixtures already commercially available, or even in foodstuff. The aim of the present study was to focus on the CLA-isomer specific effects depicted in the literature up to now.