Effects of conjugated linoleic acid on skeletal muscle triacylglycerol metabolism in hamsters

OBJECTIVE: The present work evaluated the effects of conjugated linoleic acid (CLA) on various aspects of triacylglycerol metabolism in skeletal muscle to determine the potential involvement of this tissue in the effect of CLA to decrease body fat. METHODS: Animals were randomized to three groups that were fed atherogenic diets that provided different amounts of trans-10,cis-12 CLA (0%, 0.5%, or 1%) for 6 wk. Muscle triacylglycerol, protein, water, glycogen, and DNA contents and fatty acid profile in triacylglycerols were analyzed. Lipoprotein lipase and carnitine palmitoyltransferase-I (CPT-I) activities were assessed. Triacylglycerol, glucose, and insulin concentrations were evaluated in serum. RESULTS: The high dose of CLA increased food efficiency and gastrocnemius muscle weight. CLA feeding resulted in decreased muscle triacylglycerol content without changes in protein, water, glycogen, and DNA contents or in cell size (protein/DNA ratio) and produced decreased lipoprotein lipase activity and increased CPT-I activity. No differences were found between CLA doses. CLA feeding led to the saturation of stored triacylglycerols. CONCLUSIONS: Decreased fatty acid uptake and increased fatty acid oxidation can contribute to the decreased muscle triacylglycerol content observed in hamsters fed the CLA diets. The increase in muscle fatty acid beta-oxidation might ultimately prevent storage of triacylglycerols in adipose tissue. Nevertheless, the lack of matching of lipoprotein lipase and CPT-I modifications makes it difficult to ensure that skeletal muscle is responsible, at least in part, for the effect of CLA on decreasing body fat; thus, further research is needed.     

共轭亚油酸对肿瘤细胞亚油酸代谢途径中限速酶的影响

目的采用体外细胞培养方法,研究不同浓度c9,t11-共轭亚油酸(c9,t11-CLA)对人胃腺癌细胞(SGC-7901)中亚油酸代谢途径的限速酶的影响。方法用200、100、50和25μmol／L浓度的c9,t11-CLA处理SGC-7901细胞24h,四甲基偶氮唑盐实验检测c9,t11-CLA对SGC-7901细胞增殖的抑制作用,采用逆转录聚合酶链反应检测c9,t11-CLA对SGC-7901细胞中亚油酸代谢途径的Δ6-脱氢酶、△5-脱氢酶、环氧合酶(COX)-1、COX-2和5-脂氧合酶(5-LOX)mRNA表达的影响。结果在200、100、50和25μmol／L浓度时,c9,t11-CLA对SGC-7901增殖的抑制率分别为54．3％、20．5％、10．5％、2．93％;均可下调COX-2mRNA的表达,上调Δ6-脱氢酶、COX-1mRNA的表达,但对Δ5-脱氢酶和5-LOXmRNA表达的影响不显著。结论c9,t11-CLA可通过调节Δ6-脱氢酶和COX的表达抑制肿瘤细胞的增殖,说明c9,t11-CLA通过影响亚油酸代谢途径中限速酶的基因表达而改变类二十碳烷酸的形成,推测c9,t11-CLA影响肿瘤细胞中亚油酸代谢途径的限速酶是其发挥抗癌活性的另一作用机制。     

Conjugated linolenic acid is slowly absorbed in rat intestine, but quickly converted to conjugated linoleic acid

We showed previously that alpha-eleostearic acid (alpha-ESA; 9Z11E13E-18:3) is converted to 9Z11E-conjugated linoleic acid (CLA) in rats through a Delta13-saturation reaction. To investigate this further, we examined the absorption and metabolism of alpha-ESA in rat intestine using a lipid absorption assay in lymph from the thoracic duct. In this study, we used 4 test oils [tung oil, perilla oil, CLA-triacylglycerol (TG), and pomegranate seed oil, containing alpha-ESA, alpha-linolenic acid (LnA; 9Z12Z15Z-18:3), CLA, and punicic acid (PA; 9Z11E13Z-18:3), respectively]. Emulsions containing the test oils were administered to rats, and lymph from the thoracic duct was collected over 24 h. The positional and geometrical isomerism of CLA produced by PA metabolism was determined using GC-electron impact (EI)-MS and (13)C-NMR, respectively; the product was confirmed to be 9Z11E-CLA. A part of alpha-ESA and PA was converted to 9Z11E-CLA 1 h after administration; therefore the lymphatic recoveries of alpha-ESA and PA were modified by the amount of recovered CLA. Cumulative recovery of CLA, alpha-ESA, and PA was lower than that of LnA only during h 1 (P < 0.05), and cumulative recovery of alpha-ESA and PA was significantly lower than that of LnA and CLA for 8 h (P < 0.05). Therefore, the absorption rate was LnA > CLA > alpha-ESA = PA. The conversion ratio of alpha-ESA to 9Z11E-CLA was higher than that of PA to 9Z11E-CLA over 24 h (P < 0.05). These results indicated that alpha-ESA and PA are slowly absorbed in rat intestine, and a portion of these fatty acids is quickly converted to 9Z11E-CLA.     

The change in conjugated linoleic acid concentration in blood of Japanese fed a conjugated linoleic acid diet

Conjugated linoleic acid (CLA) is a collective term used for fatty acids with a conjugated double bond that are geometrical and positional isomers of linoleic acid. Anti-obesity and anti-cancer properties, an immunopotentiation effect, and promotion of bone formation by CLA have been shown in cell culture and animal studies. A mixture of 9c11t- and 10t12c-CLA is now used as a health food supplement after testing in clinical trials. These trials focused on improvement of lipid metabolism by CLA, whereas few studies have examined absorption and metabolism of CLA in humans. In addition, there is no report concerning absorption and metabolism of CLA in Japanese. This study was designed to examine CLA concentration in blood, the elimination rate of CLA, and metabolic differences between 9c11t-CLA and 10t12c-CLA in blood in Japanese who ingested CLA (about 2 g/d, equal weights of 9c11t-CLA and 10t12c-CLA) for 3 wk. Blood samples were collected 1 wk before the 3-wk period, on the first and last days of the period, and 1 wk after the end of the period, and the CLA concentration and distribution in blood were investigated. The CLA concentration in blood was significantly increased by CLA ingestion and reached 36 μmol/L. The CLA concentration in blood one week after the intake period was significantly lower than that at the end of CLA intake. The 10t12c-CLA level in plasma decreased faster than that of 9c11t-CLA. This suggests faster metabolism (fatty acid β oxidation) of 10t12c-CLA compared with 9c11t-CLA.     

Dietary conjugated linoleic acid differentially alters fatty acid composition and increases conjugated linoleic acid content in porcine adipose tissue

Conjugated linoleic acids (CLA) have been shown to decrease body fat content in pigs. It is possible that feeding pigs diets rich in CLA may increase carcass lipid CLA to levels that could provide health benefits when included as a part of a healthy diet. Therefore, the aim of the present study was to determine whether dietary CLA supplementation has any effect on the fatty acid composition of subcutaneous and intramuscular adipose tissue in pigs. Thirty-five female cross bred (Large White x Landrace) pigs (initial weight 57.2 kg and initial P2 back fat 11.5 mm) were used in the present study. Pigs were housed individually and randomly allocated to one of six dietary treatments (0.00, 1.25, 2.50, 5.00, 7.50 and 10.00 g CLA55 (55 g CLA isomers/100 g total fatty acids; Natural Lipids Ltd, Hovdebygda, Norway)/kg) and fed their respective diets for 8 weeks. Twelve CLA isomers in the diet and in pig tissue lipids were separated by Ag+-HPLC. CLA was incorporated at fivefold higher levels in subcutaneous fat as compared with intramuscular fat and in a dose-dependant manner. Overall, the transfer efficiency of CLA was maximized at 5.00 g CLA55/kg. However, there was clear selectivity in the uptake or incorporation of cis,trans-9,11 isomer over the trans,cis-10,12 isomer. In general, CLA supplementation produced significant changes in skeletal muscle and adipose tissue fatty acid composition, indicating that dietary CLA had a potent affect on lipid transport and metabolism in vivo. Significant increases in myristic, palmitic and palmitoleic acids and a reduction in arachidonic acid were observed, suggesting an alteration in activity of delta5-, delta6- and delta9-desaturases in pig adipose tissue. In conclusion, feeding pigs diets supplemented with CLA increases carcass lipid CLA, but also results in changes in the fatty acid profile in pig fat that could potentially outweigh the benefits of CLA.     

Recent advances in conjugated linoleic acid research

New results on the physiological properties of conjugated linoleic acid have been published by several working groups, especially showing the effects of single conjugated linoleic acid isomers on carcinogenesis and body composition. Recently, other studies have shown that conjugated linoleic acid has an influence on diabetes mellitus, platelet aggregation and the immune system. Conjugated linoleic acid was found to modify prostaglandin metabolism and delta9-desaturase activity and influence apoptosis. Furthermore, improved analytical methods using 13C nuclear magnetic resonance and silver ion high performance liquid chromatography are available to investigate the composition of conjugated linoleic acid mixtures and the exact structure of separated isomers. Also, the synthesis of isolated isomers is described, as published by different authors, in order to determine further the effects of each single conjugated linoleic acid isomer. In addition, new data on the contents of conjugated linoleic acid in foods, human adipose tissue and fluids are given in this review. More data need to be obtained using isolated isomers, with particular emphasis on studies in humans.     

Alpha-linolenic acid but not conjugated linolenic acid is hypocholesterolaemic in hamsters

Conjugated linolenic acid (CLN) refers to a group of octadecatrienoic acid isomers that have three double bonds in conjugation. Both pomegranate and tung seed oils are rich in CLN but the major isomer in the former is cis9,trans11,cis13 while in the latter it is cis9,trans11,trans13. The present study examined the effects of CLN, isolated from either pomegranate seed oil or tung seed oil, and alpha-linolenic acid (LN), isolated from flaxseed oil, on serum cholesterol levels in male hamsters (body weight 105 g; age 10 weeks) fed a 0.1% cholesterol and 10% lard diet, for a period of 6 weeks. All hamsters were allowed free access to food and fluid. The blood samples were taken by bleeding from the retro-orbital sinus into a heparinized capillary tube under light ether anaesthesia after overnight fasting at weeks 0, 2, 4 and 6. It was found that supplementation of CLN at levels of 12.2-12.7 g/kg diet exhibited no significant effect on serum cholesterol level while LN at a similar level of supplementation had serum cholesterol reduced by 17-21% compared with the control diet containing no LN and CLN. Supplementation of CLN and LN significantly decreased hepatic cholesterol but no effect was observed on heart and kidney cholesterol levels. It was concluded that LN possessed hypocholesterolaemic activity while CLN had no effect on blood cholesterol, at least in hamsters.     

Effect of dietary conjugated linoleic acid isomers on lipid metabolism in hamsters fed high-carbohydrate and high-fat diets

Dietary conjugated linoleic acids (CLA) have been reported to have a number of isomer-dependent effects on lipid metabolism including reduction in adipose tissue deposition, changes in plasma lipoprotein concentrations and hepatic lipid accumulation. The aim of this study was to compare the effect of individual CLA isomers against lipogenic and high 'Western' fat background diets. Golden Syrian hamsters were fed a high-carbohydrate rodent chow or chow supplemented with 17.25 % fat formulated to represent the type and amount of fatty acids found in a typical 'Western' diet (including 0.2 % cholesterol). Diets were further supplemented with 0.25 % (w/w) rapeseed oil, cis9, trans11 (c9,t11)-CLA or trans10, cis12 (t10,c12)-CLA. Neither isomer had a significant impact on plasma lipid or lipoprotein concentrations. The t10,c12-CLA isomer significantly reduced perirenal adipose tissue depot mass. While adipose tissue acetyl CoA carboxylase and fatty acid synthase mRNA concentrations (as measured by quantitative PCR) were unaffected by CLA, lipoprotein lipase mRNA was specifically reduced by t10,c12-CLA, on both background diets (P < 0.001). This was associated with a specific reduction of sterol regulatory element binding protein 1c expression in perirenal adipose tissue (P = 0.018). The isomers appear to have divergent effects on liver TAG content with c9,t11-CLA producing lower concentrations than t10,c12-CLA. We conclude that t10,c12-CLA modestly reduces adipose tissue deposition in the Golden Syrian hamster independently of background diet and this may possibly result from reduced uptake of lipoprotein fatty acids, as a consequence of reduced lipoprotein lipase gene expression.     

共轭亚油酸抑制人胃腺癌细胞体外侵袭作用

目的 采用体外细胞培养技术，模拟体内肿瘤转移过程，研究c9，t11—共轭亚油酸(CLA)对肿瘤细胞侵袭及侵袭相关特性的影响。方法 用0，25，50，100和200μmol／LCLA处理SGC—7901人胃腺癌细胞24h后，分别进行重组基底膜侵袭试验、趋向性运动实验和粘附试验研究CLA对侵袭、运动和粘附能力的影响。结果 在200，100和50μmol／L浓度时，c9，t11—CLA对肿瘤细胞侵袭重组基底膜的抑制率分别为53．7％，40．9％和29．3％。同时，c9，t11—CLA处理后的肿瘤细胞与细胞外基质的粘附能力降低，但对肿瘤细胞趋化运动能力的影响不明显。结论 c9，t11—CLA可降低肿瘤细胞的体外侵袭能力，改变某些侵袭相关性质。     

Effects of dietary conjugated linoleic acid at high-fat levels on triacylglycerol regulation in mice

ObjectiveOur aim was to investigate the effects of dietary conjugated linoleic acid (CLA) at high-fat (HF) levels on parameters related to triacylglycerol (TG) regulation and some potential impacts on liver damage.MethodsGrowing mice were fed a control diet (7% corn oil), an HF diet containing 20% corn oil, or an HF diet containing 3% CLA (HF + CLA) for 30 d. Tissue and organ weights, plasma and tissue TG levels, and parameters related to their regulation were evaluated. Liver oxidative status was also assessed.ResultsDietary CLA showed detrimental and beneficial effects. CLA added to the HF diet caused hepatomegaly (+32%) and exacerbated the hepatic TG accumulation (+168%) observed with the HF diet without inducing liver damage; however, it significantly reduced plasma TG concentrations (?37%) and normalized muscular TG content. An increase in glutathione was associated with total normalization of liver lipid peroxidation. In addition, HF + CLA caused dystrophy of epididymal fat pads, even when the HF diet had increased the adipose tissue mass (30%). The biochemical mechanisms involved in the regulation of lipid levels were related to reduced (?20%) hepatic very low-density lipoprotein-TG secretion and decreased muscle (?35%) and adipose (?49%) tissue contributions to the removal of plasma TG by lipoprotein lipase enzymes.ConclusionExamination of CLA at HF levels showed hepatomegaly and exacerbation of lipid accretion as a negative impact; however, some positive aspects such as hypotriglyceridemia and protection against oxidative stress were also induced. Even the fat reduction is nutritionally important for weight control; the biochemical mechanisms whereby CLA mediates the potential effects could produce undesirable metabolic alterations.     

Colonic anti-inflammatory mechanisms of conjugated linoleic acid

Conjugated linoleic acid (CLA) is a mixture of positional (e.g. 7,9; 9,11; 10,12; 11,13) and geometric (cis or trans) isomers of octadecadienoic acid. This compound was first shown to prevent mammary carcinogenesis in murine models. Later investigations uncovered a number of additional health benefits, including decreasing atherosclerosis and inflammation while enhancing immune function. The mechanisms of action underlying these biological properties are not clearly understood. The aim of this review is to highlight recent advances in CLA research related to experimental inflammatory bowel disease. In addition, two possible mechanisms of action (i.e. endoplasmic and nuclear) were discussed in detail in the context of enteric inflammatory disorders. Conjugated linoleic acid was first implicated in down-regulating the generation of inducible eicosanoids (i.e. PGE(2) and LTB(4)) involved in early micro-inflammatory events (endoplasmic). More recently, CLA has been shown to modulate the expression of genes regulated by peroxisome proliferator-activated receptors (PPARs; nuclear). In pigs, prolonged dietary CLA treatment stimulated the expression of PPAR-gamma in the muscle. Thus, evidence supporting both mechanistic theories of CLA acting through eicosanoid synthesis and PPAR activity is available. The further understanding of the anti-inflammatory mechanisms of action of CLA may yield novel nutritional therapies for enteric inflammation.     

Bioconversion of vaccenic acid to conjugated linoleic acid in humans

BACKGROUND: Vaccenic acid (11-trans octadecenoic acid; VA), a major trans fatty acid in the fat of ruminants, is produced in the rumen and converted in tissues to rumenic acid (9-cis, 11-trans octadecenoic acid; RA), an isomer of conjugated linoleic acid, by Delta(9)-desaturase. There are indications that this conversion also occurs in humans. OBJECTIVE: The aim of this controlled intervention was to study the conversion of VA to RA in humans after consumption of diets with increasing amounts of VA. DESIGN: Thirty healthy subjects consumed a baseline diet rich in oleic acid for 2 wk. The subjects were then divided into 3 groups (n = 10 per group) and provided a diet containing 1.5, 3.0, or 4.5 g VA/d for 9 d. All diets contained equal amounts of macronutrients and differed only in their fatty acid compositions. The fats were mixed into conventional foods, and nearly all food was provided during the study. RESULTS: The proportion of VA in serum total fatty acids increased 94%, 307%, and 620% above baseline with the 1.5-, 3.0-, and 4.5-g diets, respectively. This was associated with a linear increase in the proportion of RA. The conversion rate was 19% on average, with significant interindividual differences with all 3 intakes of VA. The urinary excretion of 8-iso-prostaglandin F(2alpha) increased in all groups (P < 0.001). CONCLUSIONS: The results quantify the desaturation of VA to RA in humans. Conversion is likely to contribute significantly to the amount of RA available to the body, and dietary intakes of VA should thus be taken into account when predicting RA status.     

Effects of dietary conjugated linoleic acid on fatty acid composition and cholesterol content of hen egg yolks

The main objectives of the present study were to determine the effect of dietary conjugated linoleic acid (CLA) isomers on the fatty acid composition and cholesterol content of egg-yolk lipids. Forty-five 25-week-old laying hens were randomly distributed into five groups of nine hens each and maintained in individual laying cages, throughout 12 weeks of the experiment. They were assigned to the five treatments that consisted of commercial layer diets containing 0, 5, 10, 15 or 20 g pure CLA/kg. Feed intake of hens varied little and insignificantly. Egg mass was uniformly lower (P<0.05) in the hens fed the CLA-enriched diets. Feed conversion efficiency, when expressed per kg eggs, was impaired (P<0.05), although without obvious relation to the dietary CLA concentration. Feeding the CLA-enriched diets resulted in gradually increasing deposition of CLA isomers (P<0.01) in egg-yolk lipids. Saturated fatty acids were increased (P<0.01) and monounsaturated fatty acids decreased (P<0.01). Polyunsaturated fatty acids (PUFA), when expressed as non-CLA PUFA, were also significantly decreased (P<0.01). The most striking effects (P<0.01) were observed for palmitic (16 : 0) and stearic (18 : 0) acids, which increased from 23.6 to 34 % and from 7.8 to 18 %, respectively. On the other hand, oleic acid (18 : 1n-9) decreased from 45.8 to 24.3 %. Among non-CLA PUFA, linoleic (18 : 2n-6) and alpha-linolenic (18 : 3n-3) acids were strongly (P<0.01) decreased, from 14.2 to 7.7 % and from 1.3 to 0.3 %, respectively. The same was true for arachidonic (20:4n-6) and docosahexaenoic (22 : 6n-3) acids. The cholesterol content of egg yolks, when expressed in mg/g yolk, was not affected by the dietary CLA concentrations. In conclusion, unless the adverse effects of CLA feeding to laying hens on the fatty acid profile of egg yolks are eliminated, the CLA-enriched eggs cannot be considered functional food products.     

Changes in body composition with conjugated linoleic acid

Conjugated linoleic acid has been shown to reduce body fat accumulation in several animal models. We have conducted several studies in AKR/J mice showing that CLA reduces body fat accumulation whether animals are fed a high-fat or low-fat diet, with no effect on food intake. One mechanism by which CLA reduces body fat is by increased energy expenditure, which is observed within one week of CLA feeding and is sustained for at least six weeks. The increased energy expenditure is sufficient to account for the decreased fat accumulation. Increased uncoupling protein gene expression does not appear to be involved in the increased energy expenditure. We have observed increased fat oxidation but no decrease in de novo fat biosynthesis with CLA feeding. We have also observed increased liver weights and plasma insulin levels with higher doses of CLA. In all of the studies we have conducted to date we have used a CLA preparation that contains several isomers, primarily c9,t11 and t10,c12. It was assumed that the active form was c9,t11, as CLA was identified as an anticarcinogenic compound from cooked beef, of which the c9,t11 form accounts for 60% to 80% of the CLA. Most of the studies conducted so far must be repeated using the purified isomers in order to determine which isomers are responsible for each of the identified actions of CLA.     

共轭亚油酸对鼠黑色素瘤细胞转移特性的影响

:采用体外培养技术 ,模拟体内肿瘤转移过程 ,研究共轭亚油酸 (conjugated linoliec acid,CL A)对鼠黑色素瘤 B16 - MB高转移细胞系的转移特性 ,从而探讨 CL A预防肿瘤转移的可能途径。研究结果表明 ,剂量为 10 0 μmol/ L、2 0 0 μmol/ L 的 CL A可抑制肿瘤细胞增殖、恢复肿瘤细胞间通讯功能、抑制肿瘤细胞向细胞外基质成分 [层粘连蛋白 (fibronectin,FN)和纤维粘连蛋白 (laminin,L N) ]的黏附。