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.     

Conjugated linoleic acid isomers and trans fatty acids inhibit fatty acid transport in hepatoma 7288CTC and inguinal fat pads in Buffalo rats

Conjugated linoleic acid (CLA) and some trans fatty acids (FA) decrease tumor growth and alter tumor and host lipid uptake and storage. The goal of this study was to test the hypothesis that the acute inhibitory effects of CLA isomers and trans FAs on FA transport in tumors and white adipose tissue are mediated via an inhibitory G-protein coupled (GPC), FFA receptor (FFAR). Experiments were performed in hepatoma 7288CTC and inguinal fat pads in Buffalo rats during perfusion in situ. CLA isomers and trans FAs (0.03-0.4 mmol/L, in plasma) were added to the arterial blood, and FA uptake or release was measured by arterial minus venous difference. In hepatoma 7288CTC, the CLA isomers, t10,c12-CLA > (+/-)-9-HODE [13-(S)-hydroxyoctadecadienoic acid] > t9,t11-CLA, and the trans FAs, linolelaidic = vaccenic > elaidic, decreased cAMP content and inhibited FA uptake, 13(S)-HODE release, extracellular signal-regulated kinase p44/p42 phosphorylation, and [(3)H]thymidine incorporation. Other CLA isomers, c9,t11-CLA, 13-(S)-HODE, c9,c11-CLA, and c11,t13-CLA, had no effect. In inguinal fat pads, FA transport was inhibited by t10,c12-CLA = linolelaidic acid > trans vaccenic acid, whereas c9,t11-CLA had no effect. In both hepatoma 7288CTC and inguinal fat pad, addition of either pertussis toxin or 8-Br-cAMP to the arterial blood reversed the inhibitions of FA transport. These results support the idea that an inhibitory GPC FFAR reduces cAMP and controls FA transport by CLA isomers and trans FAs. Ligand activity is conferred by the presence of a trans double bond proximal to the carboxyl group.     

市售牛奶中c9,t11-共轭亚油酸测定的气相色谱法研究

目的：用气相色谱内标法检测部分市售牛奶中c9，t11-共轭亚油酸含量（CLA），分析季节因素对牛奶中e9，t11-共轭亚油酸含量的影响。方法：采用气相色谱内标法，内标物为C17：00甲酯，程序升温，将样品提取、甲酯化后，测定并比较夏季和非夏季牛奶样品中c9，t11-共轭亚油酸的含量。结果：实验方法的回收率为83．67％，RSD=3．45％；精密度为RSD=2．09％。夏季和非夏季牛奶样品中c9，t11-共轭亚油酸含量均值范围分别为0～14．9me,／g脂肪和0～7．3mg／g脂肪。夏季牛奶样品中c9，t11-共轭亚油酸含量显著高于非夏季牛奶样品（P〈0．05）。结论：所建立的实验条件准确可靠，季节变化对牛奶样品中c9，t11-共轭亚油酸含量有显著影响。本研究对在国内开展共轭亚油酸强化乳制品的研究具有指导意义。     

Conjugated linoleic acid isomers and cancer

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.     

The conjugated linoleic acid (CLA) isomer,t10c12-CLA,is inversely associated with changes in body weight and serum leptin in subjects with type 2 diabetes mellitus

Isomers of conjugated linoleic acid (CLA) are found in beef, lamb and dairy products. Diets containing CLA reduce adipose mass in various depots of experimental animals. In addition, CLA delays the onset of diabetes in the ZDF rat model for obesity-linked type 2 diabetes mellitus. We hypothesize that there would be an inverse association of CLA with body weight and serum leptin in subjects with type 2 diabetes mellitus. In this double-blind study, subjects with type 2 diabetes mellitus were randomized into one of two groups receiving either a supplement containing mixed CLA isomers (CLA-mix; 8.0 g daily, 76% pure CLA; n = 12) or a supplement containing safflower oil (placebo; 8.0 g daily safflower oil, n = 9) for 8 wk. The isomers of CLA in the CLA-mix supplement were primarily c9t11-CLA ( approximately 37%) and t10c12-CLA ( approximately 39%) in free fatty acid form. Plasma levels of CLA were inversely associated with body weight (P < 0.05) and serum leptin levels (P < 0.05). When levels of plasma t10c12-CLA isomer were correlated with changes in body weight or serum leptin, t10c12-CLA, but not c9t11-CLA, was inversely associated with body weights (P < 0.05) and serum leptin (P < 0.02). These findings strongly suggest that the t10c12-CLA isomer may be the bioactive isomer of CLA to influence the body weight changes observed in subjects with type 2 diabetes. Future studies are needed to determine a causal relationship, if any, of t10c12-CLA or c9t11-CLA to modulate body weight and composition in subjects with type 2 diabetes. Furthermore, determining the ability of CLA isomers to influence glucose and lipid metabolism as well as markers of insulin sensitivity is imperative to understanding the role of CLA to aid in the management of type 2 diabetes and other related conditions of insulin resistance.     

Antiproliferative effects of conjugated linoleic acid on human colon adenocarcinoma cell line Caco-2

Conjugated linoleic acid (CLA) reduces body fat reserves, and reduces atherogenesis and type II diabetes in animal experiments. It has been reported that CLA have isomeric-specificity, such as c9, t11 CLA with anticancer activity. The antiproliferative effects of two isomers of CLA (c9, t11-CLA, t9, t11-CLA) and their mixture on the human colon adenocarcinoma cell line Caco-2 were investigated in this paper. Caco-2 were incubated in serum-free medium. The antiproliferative effects of different concentrations (0, 25, 50, 100, 200 micromol/L) of linoleic acid (LA), c9, t11-CLA, t9, t11-CLA (the purity of LA and CLA was 96%) and a mixture of c9, t11-CLA and t9, t11- CLA (1:1 v/v) on caco-2 in various action time (1d, 2d, 3d, 4d) were tested in the present study. The antiproliferative effects of four substances in the same concentration and with the same action time were compared. All substances tested could inhibit Caco-2 cell proliferation. The higher anti-proliferation activity in the four materials is the mixture of CLA, then is t9,t11-CLA, c9,t11-CLA, and linoleic acid respectively. The activity is closely related to treatment time and concentration. The isomer t9, t11-CLA itself was found to have antiproliferative activity.     

Chronic but not acute treatment with conjugated linoleic acid (CLA) isomers (trans-10, cis-12 CLA and cis-9, trans-11 CLA) affects lipid metabolism in Caco-2 cells

Conjugated linoleic acid (CLA) has profound effects on hepatic and adipocyte lipid metabolism, but little is known about its effects on intestinal lipid metabolism. We investigated the acute (22 h) and acute-after-chronic (22 h after 19 d) effects of trans-10, cis-12 CLA (t10,c12-CLA) and cis-9, trans-11 CLA (c9, t11-CLA) on triacylglycerol (TAG)-rich lipoprotein (TRL) metabolism, de novo TAG, phospholipid (PL) ((14)C-glycerol) and apolipoprotein B (apoB) ((35)S-methionine) synthesis and secretion, in the colon carcinoma (Caco-2) cell model of intestinal lipoprotein metabolism. Acute treatment with either CLA isomer did not affect TRL metabolism. However, chronic t10,c12-CLA and c9,t11-CLA supplementation followed by acute palmitic acid (PA) treatment increased the ratio of cellular to secreted de novo TAG (cTAG/sTAG) (P < or = 0.03) as a result of increased cellular de novo TAG levels. Chronic Caco-2 cell t10,c12-CLA supplementation, prior to the acute oleic acid (OA) treatment, significantly increased (P = 0.005) the ratio of cellular de novo TAG to de novo PL (cTAG/cPL), to a greater extent than that following chronic linoleic acid (LA) (P = 0.001) or c9,t11-CLA supplementation (P = 0.005). Again, this effect was attributed to increased cellular de novo TAG synthesis. Neither CLA isomer affected the ratio of secreted de novo TAG to de novo PL (sTAG/sPL). No effects on Caco-2 cell apoB synthesis and secretion were observed after acute or chronic CLA treatments. In conclusion, chronic t10,c12-CLA supplementation modulated intestinal TRL metabolism, by increasing cellular de novo TAG synthesis but had no effect on de novo TAG secretion in Caco-2 cells.     

Effects of ruminant trans fatty acids on cardiovascular disease and cancer: a comprehensive review of epidemiological, clinical, and mechanistic studies

There are 2 predominant sources of dietary trans fatty acids (TFA) in the food supply, those formed during the industrial partial hydrogenation of vegetable oils (iTFA) and those formed by biohydrogenation in ruminants (rTFA), including vaccenic acid (VA) and the naturally occurring isomer of conjugated linoleic acid, cis-9, trans-11 CLA (c9,t11-CLA). The objective of this review is to evaluate the evidence base from epidemiological and clinical studies to determine whether intake of rTFA isomers, specifically VA and c9,t11-CLA, differentially affects risk of cardiovascular disease (CVD) and cancer compared with iTFA. In addition, animal and cell culture studies are reviewed to explore potential pro- and antiatherogenic mechanisms of VA and c9,t11-CLA. Some epidemiological studies suggest that a positive association with coronary heart disease risk exists between only iTFA isomers and not rTFA isomers. Small clinical studies have been conducted to establish cause-and-effect relationships between these different sources of TFA and biomarkers or risk factors of CVD with inconclusive results. The lack of detection of treatment effects reported in some studies may be due to insufficient statistical power. Many studies have used doses of rTFA that are not realistically attainable via diet; thus, further clinical studies are warranted. Associations between iTFA intake and cancer have been inconsistent, and associations between rTFA intake and cancer have not been well studied. Clinical studies have not been conducted investigating the cause-and-effect relationship between iTFA and rTFA intake and risk for cancers. Further research is needed to determine the health effects of VA and c9,t11-CLA in humans.     

Immunological and metabolic effects of cis-9, trans-11-conjugated linoleic acid in subjects with birch pollen allergy

Animal studies suggest that conjugated linoleic acid (CLA) may modulate the immune response, while studies in healthy human subjects have shown little effect and results are controversial. However, the effects of CLA may be more prominent in situations of immune imbalance, such as allergy. We studied the effects of the natural CLA isomer, cis-9, trans-11-CLA, on allergy symptoms and immunological parameters in subjects with birch pollen allergy. In a randomised, placebo-controlled study, forty subjects (20-46 years) with diagnosed birch pollen allergy received 2 g CLA/d in capsules, which contained 65.3 % cis-9, trans-11-CLA and 8.5 % trans-10, cis-12-CLA (n 20), or placebo (high-oleic acid sunflower-seed oil) (n 20) for 12 weeks. The supplementation began 8 weeks before the birch pollen season and continued throughout the season. Allergy symptoms and use of medication were recorded daily. Lymphocyte subsets, cytokine production, immunoglobulins, C-reactive protein, lipid and glucose metabolism and lipid peroxidation were assessed before and after supplementation. The CLA group reported a better overall feeling of wellbeing (P < 0.05) and less sneezing (P < 0.05) during the pollen season. CLA supplementation decreased the in vitro production of TNF-alpha (P < 0.01), interferon-gamma (P < 0.05) and IL-5 (P < 0.05). Total plasma IgE and birch-specific IgE concentrations did not differ between groups, whereas plasma IgA (P < 0.05), granulocyte macrophage colony-stimulating factor (P < 0.05) and eosinophil-derived neurotoxin (P < 0.05) concentrations were lower after CLA supplementation. Urinary excretion of 8-iso-PGF2alpha, a major F2-isoprostane (P < 0.01), and 15-keto-dihydro-PGF2alpha, a primary PGF2alpha metabolite (P < 0.05), increased in the CLA group. The results suggest that cis-9, trans-11-CLA has modest anti-inflammatory effects in allergic subjects.     

Trans-10, cis-12- and cis-9, trans-11-conjugated linoleic acid isomers selectively modify HDL-apolipoprotein composition in apolipoprotein E knockout mice

Trans-10, cis-12-conjugated linoleic acid (CLA)-enriched diets promote atherosclerosis in mice despite increasing blood concentrations of HDL cholesterol. This suggests that under these conditions, the HDL apolipoproteins (apo) produced are abnormal. To test this hypothesis, apoE-deficient mice were fed a Western-type diet enriched with linoleic acid (control), cis-9, trans-11-CLA or trans-10, cis-12-CLA (1.0% wt/wt) for 12 wk, and the effects on HDL metabolism and apoC-III levels recorded. Compared with the control and cis-9, trans-11-CLA mice, those fed the trans-10, cis-12-CLA diet had significantly higher HDL cholesterol concentrations, and had a higher incidence of hypertriglyceridemia and hepatic steatosis. Plasma apoA-I and paraoxonase concentrations were significantly lower in the trans-10, cis-12-CLA group than in the cis-9, trans-11-CLA group. These reductions were associated with decreased hepatic expression of these proteins and a shift toward lipid-poor apolipoprotein particles. The plasma apoA-II concentration increased with its corresponding mRNA concentration in the liver, and was preferentially bound to HDL in the trans-10, cis-12-CLA mice, thus explaining the increased HDL cholesterol concentrations in this group. Significant, positive associations were found between apoA-II and C-III (r=0.883, P<0.001) and between apoA-II and atherosclerosis (r=0.68, P<0.001). These results indicate that trans-10, cis-12-CLA intake modifies HDL to form a proatherogenic apoA-II containing particle and promotes phenotypic changes compatible with metabolic syndrome. Cis-9, trans-11-CLA does not promote this detrimental effect.     

Conjugated linoleic acid (CLA)-enriched milk fat inhibits growth and modulates CLA-responsive biomarkers in MCF-7 and SW480 human cancer cell lines

Milk enriched in conjugated linoleic acid (CLA) was obtained from cows on pasture supplemented with full-fat rapeseeds (FFR; 2.26 g cis 9, trans 11 (c9,t11)-CLA/100 g fatty acid methyl esters) and full-fat soyabeans (1.83 g c9,t11-CLA100 g fatty acid methyl esters). A control milk fat (1.69 g c9,t11-CLA/100 g fatty acid methyl esters) was obtained from cows fed on pasture only. The present study assessed the potency of the CLA-enriched milk fats to modulate biomarkers that had previously been observed to respond to c9,t11-CLA in the MCF-7 and SW480 cell lines. Cell numbers decreased (P<0.05) by up to 61 and 58% following the incubation of MCF-7 and SW480 cells, respectively, for 4 d with milk fats (yielding CLA concentrations between 60.2 and 80.6 microM). The FFR milk fat, containing the highest CLA content, increased (P<0.05) [14C]arachidonic acid (AA) uptake into the monoacylglycerol fraction of MCF-7 and SW480 cells while it decreased (P<0.05) uptake into the phospholipid fraction of the latter. This milk fat also decreased (P<0.05) [14C]AA conversion to prostaglandin (PG) E2 while increasing conversion to PGF2alpha in both cell lines. All milk-fat samples increased (P<0.05) lipid peroxidation as measured by 8-epi-PGF2alpha in both cell lines. In SW480 cells the milk-fat samples decreased (P<0.05) bcl-2 and cytosolic glutathione levels while increasing (P<0.05) membrane-associated annexin V levels. All milk-fat samples decreased (P<0.05) the expression of ras in SW480 cells. These data suggest that milk-fat CLA was effective at modulating synthetic CLA-responsive biomarkers.     

Effects of conjugated linoleic acid on linoleic and linolenic acid metabolism in man

Evidence from animal studies suggests that conjugated linoleic acid (CLA) modulates plasma and tissue appearance of newly synthesized PUFA. The effects of a 1.2g (0.5 % energy) daily intake of the cis-9,trans-11 (c9,t11) isomer of CLA, trans-10,cis-12 (t10,c12) isomer of CLA or olive oil (placebo) on linoleic acid (LA) and linolenic acid (LNA) metabolism in healthy human volunteers was investigated. Fifteen subjects were fed an experimental diet and supplemented with c9,t11-CLA, t10,c12-CLA or placebo for 7 d before consuming a tracer dose of U-[(13)C]LA (50 mg) and U-[(13)C]LNA (50 mg). Blood samples were taken at 0, 2, 4, 6, 8, 24, 48, 72 and 168 h and analysed using high-precision MS. No differences between the groups in peak plasma [(13)C]LA (10.3-11.6 % of dose), [(13)C]LNA (2.5-2.9 % of dose), [(13)C]arachidonic acid (0.09-0.12 % of dose), [(13)C]EPA (0.04-0.06 % of dose) or [(13)C]DHA (0.06-0.10 % of dose) were detected. Concentration v. time curves (area under the curve) also showed no significant differences between groups. This suggests that, in healthy human subjects consuming a diet with adequate intake of essential fatty acids, CLA does not affect metabolism of LA or LNA.     

Conjugated linoleic acid-enriched butter fat alters mammary gland morphogenesis and reduces cancer risk in rats

Conjugated linoleic acid (CLA) is a potent cancer preventive agent in animal models. To date, all of the in vivo work with CLA has been done with a commercial free fatty acid preparation containing a mixture of c9,t11-, t10,c12- and c11,t13-isomers, although CLA in food is predominantly (80-90%) the c9,t11-isomer present in triacylglycerols. The objective of this study was to determine whether a high CLA butter fat has biological activities similar to those of the mixture of free fatty acid CLA isomers. The following four different endpoints were evaluated in rat mammary gland: 1) digitized image analysis of epithelial mass in mammary whole mount; 2) terminal end bud (TEB) density; 3) proliferative activity of TEB cells as determined by proliferating cell nuclear antigen immunohistochemistry; and 4) mammary cancer prevention bioassay in the methylnitrosourea model. It should be noted that TEB cells are the target cells for mammary chemical carcinogenesis. Feeding butter fat CLA to rats during the time of pubescent mammary gland development reduced mammary epithelial mass by 22%, decreased the size of the TEB population by 30%, suppressed the proliferation of TEB cells by 30% and inhibited mammary tumor yield by 53% (P < 0.05). Furthermore, all of the above variables responded with the same magnitude of change to both butter fat CLA and the mixture of CLA isomers at the level of CLA (0.8%) present in the diet. Interestingly, there appeared to be some selectivity in the uptake or incorporation of c9,t11-CLA over t10,c12-CLA in the tissues of rats given the mixture of CLA isomers. Rats consuming the CLA-enriched butter fat also consistently accumulated more total CLA in the mammary gland and other tissues (four- to sixfold increases) compared with those consuming free fatty acid CLA (threefold increases) at the same dietary level of intake. We hypothesize that the availability of vaccenic acid (t11-18:1) in butter fat may serve as the precursor for the endogenous synthesis of CLA via the Delta9-desaturase reaction. Further studies will be conducted to investigate other attributes of this novel dairy product.     

共轭亚油酸对正常动物细胞和人体肿瘤细胞间通讯功能的影响

为探讨c9,t11-共轭亚油酸 (CLA)的抑癌作用可能机制 ,在促癌物 (TPA)存在下 ,对正常细胞(CHL)以及人体肿瘤细胞 (SGC 790 1细胞和MCF 7细胞 )的细胞间隙连接通讯功能 (GJIC)的影响 ,采用划痕标记染料示踪技术 (SLDT) ;c9,t11 CLA剂量为 2 5 (mol L ,5 0 (mol L ,10 0 (mol L和 2 0 0 (mol L ,阴性对照为乙醇。结果显示 ,c9,t11 CLA可明显地提高TPA对CHL细胞的GJIC的抑制效应 ,当c9,t11 CLA浓度为 2 0 0 (mol L作用 48h时 ,细胞间隙通讯功能基本上与阴性对照组相近 ;当用c9,t11 CLA作用SGC 790 1细胞和MCF 7细胞2 4h和 48h时 ,可见 (2 4h 10 0 μmol L的MCF 7细胞 ) 2 4h 2 0 0 μmol L和 48h 10 0、2 0 0 μmol L剂量组的肿瘤细胞有一定的细胞间隙通讯功能。提示c9,t11 CLA可提高SGC 790 1细胞和MCF 7细胞的GJIC的功能 ,并且不同程度的拮抗TPA对CHL细胞GJIC的抑制效应     

Effects of cis-9,trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men

BACKGROUND: We recently showed that trans-10,cis-12 (t10,c12) conjugated linoleic acid (CLA) causes insulin resistance in obese men. However, metabolic effects of the c9,t11 CLA isomer are still unknown in obese men. Because c9,t11 CLA is the predominant CLA isomer in foods and is included in dietary weight-loss products, it is important to conduct randomized controlled studies that use c9,t11 CLA preparations. OBJECTIVE: We investigated the effects of c9,t11 CLA supplementation on insulin sensitivity, body composition, and lipid peroxidation in a group at high risk for cardiovascular disease. DESIGN: In a randomized, double-blind, placebo-controlled study, 25 abdominally obese men received 3 g c9,t11 CLA/d or placebo (olive oil). Before and after 3 mo of supplementation, we assessed insulin sensitivity (hyperinsulinemic euglycemic clamp), lipid metabolism, body composition, and urinary 8-iso-prostaglandin F(2alpha) (a major F(2)-isoprostane) and 15-keto-dihydro-prostaglandin F(2alpha), markers of in vivo oxidative stress and inflammation, respectively. RESULTS: All subjects completed the study. Compared with placebo, c9,t11 CLA decreased insulin sensitivity by 15% (P < 0.05) and increased 8-iso-prostaglandin F(2alpha) and 15-keto-dihydro-prostaglandin F(2alpha) excretion by 50% (P < 0.01) and 15% (P < 0.05), respectively. The decreased insulin sensitivity was independent of changes in serum lipids, glycemia, body mass index, and body fat but was abolished after adjustment for changes in 8-iso-prostaglandin F(2alpha) concentrations. There were no differences between groups in body composition. CONCLUSIONS: A CLA preparation containing the purified c9,t11 CLA isomer increased insulin resistance and lipid peroxidation compared with placebo in obese men. Because c9,t11 CLA occurs in commercial supplements as well as in the diet, the present results should be confirmed in larger studies that also include women.     

An isomeric mixture of conjugated linoleic acids but not pure cis-9, trans-11-octadecadienoic acid affects body weight gain and plasma lipids in hamsters

We report the effect of an atherogenic diet supplemented with cis-9, trans-11-octadecadienoic acid (c9t11), linoleic acid (LA) or an isomeric mixture of conjugated linoleic acids (CLA) on plasma lipids, weight gain and food intake of male Golden Syrian hamsters. Animals were assigned to three diet groups (n = 10), and fed nonpurified diet, supplemented with 10% hydrogenated coconut oil and 0.05% cholesterol for 6 wk. The first diet group was further supplemented with 1% CLA (CLA group), the second diet group with 0.2% c9t11 (c9t11 group) and the third group with 0.2% LA (LA group). The diets were designed to have equivalent levels of c9t11 in the CLA and c9t11 groups. At 2 and 6 wk of feeding, the CLA group had significantly lower plasma triglyceride and total cholesterol concentrations than either the c9t11 or the LA groups. HDL-cholesterol did not differ among diet groups. The CLA group had significantly lower weight gain but greater food intake than either the c9t11 or the LA groups. There were no significant differences between the c9t11 and the LA groups in any of the variables measured. We conclude that under our experimental conditions of short-term feeding, c9t11, thought to be the active compound in CLA, does not produce the same effect as the isomer mixture.     

cis-9, trans-11 conjugated linoleic acid is synthesized directly from vaccenic acid in lactating dairy cattle

The utilization of (13)C-labeled vaccenic acid (VA) by lactating dairy cows to synthesize cis-9, trans-11 conjugated linoleic acid (CLA) was investigated. Primiparous ruminally cannulated Holstein cows (n = 3) were abomasally infused with 1.5 g of VA-1-(13)C. Blood and milk samples were taken frequently before and after VA infusion. Milk and plasma lipid were extracted using chloroform:methanol. Plasma lipid was separated into triacylglycerol (TG), cholesterol ester (CE), phospholipid (PL), nonesterified fatty acid (NEFA), and mono- and diacylglycerol (MDG) fractions. Lipid was methylated, converted to dimethyl disulfide and Diels-Alder adducts, and analyzed by GC-MS. Increased enrichment of (13)C was determined using a 2-sample t test for each sample time compared with -24 h, with significance declared at P < 0.05. Enrichment in milk fat VA was detected at 4 (3.0%), 8 (8.3%), 12 (4.1%), 16 (2.2%), and 20 h (0.8%). Enrichment in VA was also detected in plasma TG, NEFA, PL, and MDG. Enrichment in milk fat cis-9, trans-11 CLA, the Delta9-desaturase product of VA, was detected at 4 (2.6%), 8 (6.6%), 12 (3.4%), 16 (1.7%), and 24 h (0.7%). Enrichment was not detected in cis-9, trans-11 CLA for any plasma lipid fraction. Modeling of the data showed the exponential decay in (13)C enrichment over time for both VA and cis-9, trans-11 CLA in milk fat. Conversion of dietary VA to cis-9, trans-11 CLA endogenously was confirmed with the mammary gland being the primary site of Delta9-desaturase activity; approximately 80% of milk fat cis-9, trans-11 CLA originated from VA.