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PubMed2005

Short-term feeding of conjugated linoleic acid does not induce hepatic steatosis in C57BL/6J mice.

We investigated the effect of short-term feeding of conjugated linoleic acid (CLA) on adipose tissue weights, liver weight, hepatic lipid metabolism, and serum lipoprotein profiles in C57BL/6J mice. Mice were fed semi-synthetic diets containing either 6%, high-linoleic safflower oil (HL-SAF) or 4% HL-SAF+2% CLA for 1 wk. Short-term feeding of CLA showed an anti-obesity effect without inducing hepatomegaly in mice. In addition to the decline of hepatic triglyceride concentration, significant inhibition of A9 desaturation of fatty acid in the total liver lipids was found in CLA-fed mice. The CLA diet significantly increased the activities of peroxisomal beta-oxidation and decreased the activities of diacylglycerol acyltransferase, a triglyceride synthesis-related enzyme, in the liver. Moreover, serum lipoprotein profiles of CLA-fed mice showed preferable changes in the atherogenic indices. However, serum leptin and adiponectin were drastically decreased by CLA feeding, suggesting that prolonged administration of CLA would induce further decrease of serum adipocytokine levels, which may be a cause of lipodystrophy in mice. These results show that short-term feeding of CLA does not induce adverse effect in C57BL/6J mice.

Adipose Tissue↗
PubMed2003

Formation of conjugated linoleic acids in soybean oil during hydrogenation with a nickel catalyst as affected by sulfur addition.

The effects of sulfur addition on the formation of conjugated linoleic acid (CLA) isomers were studied during the hydrogenation of soybean oil with a nonselective type nickel catalyst. Sulfur addition greatly promoted CLA formation in soybean oil during hydrogenation. As the amount of sulfur increased to a certain level, the maximal quantity of CLA in soybean oil during hydrogenation increased greatly. However, further increase in sulfur addition above the certain level decreased CLA formation. The optimal sulfur level for the promotion of CLA formation differed greatly with the amount of nickel used. It was of great interest to find that the optimal ratio of sulfur to nickel for the promotion of CLA formation was always 0.06:1, regardless of the nickel amount used. At the same ratio of sulfur to nickel, higher nickel content induced significantly higher production of CLA (p < 0.05). At the optimal sulfur to nickel ratio, an increase in the nickel amount from 0.05 to 0.15% produced approximately 1.5 times higher levels of CLA during hydrogenation under the tested conditions. The CLA isomer compositions were greatly affected by both sulfur addition and amounts of nickel used for treatment. This is the first report of the possibility that the total quantity of CLA and their isomer composition could be manipulated during hydrogenation by controlling the amounts of sulfur and nickel.

Catalysis↗
PubMed2000

Dietary conjugated linoleic acid reduces rat adipose tissue cell size rather than cell number.

We investigated the basis for the reduction in fat pad size in rats fed conjugated linoleic acid (CLA). In the first study, growing female Sprague-Dawley rats (initial weight150 g) were fed diets containing 0, 0.25 and 0.5 g/100 g diet of a purified (97% CLA) and 0.5% of a feed-grade (55% CLA) source of CLA for 5 wk to determine the effects on growth performance and fat mass. There was no effect of CLA on growth rate or food intake. Dietary CLA reduced retroperitoneal fat pad weight 13, 25 and 32% in rats fed 0.25 and 0. 5% of the pure CLA and 0.5% of the feed-grade CLA, respectively (P < 0.05). Similar effects were observed in the parametrial fat pad. The reduced pad size was due to smaller adipocyte size rather than a reduced cell number. Relative to the control group, mean cell volume was 15, 28 and 29% lower in tissue from rats fed 0.25 and 0.5% of the pure CLA and 0.5% of the feed-grade CLA, respectively (P < 0.01). In the second study, rats were fed CLA (0 vs. 0.5%) for 7 or 49 d. Reductions in fat pad weight were observed within 7 d. In addition, the effects of CLA on energy metabolism were studied in the chronically fed rats. There were no significant effects of CLA on oxygen consumption, CO(2) or heat production. During wk 4 of feeding, but not at other times, there was a 5% lower respiratory quotient in CLA-fed rats (P < 0.05). There was a time-dependent accumulation of CLA in adipose tissue and a decrease in monounsaturated fatty acids. These results suggest that the reduction in fat mass in rats fed CLA can be accounted for by a reduction in cell size rather than a change in cell number.

Adipose Tissue↗
PubMed2005

Conjugated linoleic acid attenuates the production and gene expression of proinflammatory cytokines in weaned pigs challenged with lipopolysaccharide.

We investigated the anti-inflammatory role of conjugated linoleic acid (CLA) in inflammation-challenged weaned pigs and in in vitro cultured peripheral blood mononuclear cells (PBMCs). To test the hypothesis that inflammation responses can be attenuated by dietary CLA supplementation, we used an acute inflammation model in which pigs were injected with lipopolysaccharide (LPS). After 14 d of dietary supplementation with either 2% soybean oil or 2% CLA, half of the pigs in each diet group were challenged with LPS. Dietary CLA alleviated growth depression and prevented the elevations in production and mRNA expression of proinflammatory cytokines [i.e., interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha] induced by the LPS challenge. CLA enhanced the expression of interleukin-10 (IL-10) and peroxisome proliferator-activated receptor-gamma (PPARgamma) in spleen and thymus. To further elucidate the inhibitory effects and the mechanism of action of CLA on cytokine profiles (i.e., IL-1beta, IL-6, and TNF-alpha), PBMCs were isolated from weaned pigs and cultured in media containing cis-9, trans-11 (9c,11t) CLA and trans-10, cis-12 (10t,12c) CLA. Each CLA isomer suppressed the production and expression of IL-1beta, IL-6, and TNF-alpha, and enhanced PPARgamma activation and gene expression in cultured PBMCs. At the molecular level, the inhibitory actions of CLA on IL-1beta, IL-6, and TNF-alpha are attributable mainly to 10t,12c-CLA and the anti-inflammatory properties of CLA are mediated, at least in part, through a PPARgamma-dependent mechanism.

Animals↗
PubMed2005

Hyperinsulinaemia triggered by dietary conjugated linoleic acid is associated with a decrease in leptin and adiponectin plasma levels and pancreatic beta cell hyperplasia in the mouse.

AIMS/HYPOTHESIS: Dietary supplementation with conjugated linoleic acids (CLA) has a fat-reducing effect in various species, but induces severe hyperinsulinaemia and hepatic steatosis in the mouse. This study aimed to determine the causes of the deleterious effects of CLA on insulin homeostasis. METHODS: The chronology of adipose and liver weight, hepatic triglyceride accumulation and selected blood parameters, including lipids, insulin, leptin and adiponectin, was determined in C57BL/6J female mice fed a 1% isomeric mixture of CLA for various periods of time ranging from 2 to 28 days. Insulin secretion was measured in 1-h static incubations of pancreatic islets, and pancreas morphometric parameters were determined in mice fed CLA for 28 days. RESULTS: Plasma levels of leptin and adiponectin sharply decreased after 2 days of CLA feeding, although adipose tissue mass only decreased after day 6. Hyperinsulinaemia developed at day 6 and consistently worsened up to day 28, in parallel with increases in hepatic lipid content. Islets from CLA-fed mice displayed three- to four-fold increased rates of glucose-stimulated insulin secretion, both in the absence and presence of isobutyl methylxanthine or carbachol. The increased insulin-releasing capacity of islets from CLA-fed mice was explained by an increase in beta cell mass and number. CONCLUSIONS/INTERPRETATION: The data suggest that CLA supplementation induces a profound reduction of leptinaemia and adiponectinaemia, followed by hyperinsulinaemia due to the increased secretory capacity of pancreatic islets, leading, in turn, to liver steatosis. These observations cast doubt on the safety of dietary supplements containing CLA.

Adiponectin↗
PubMed2002

Effects of dietary fat and conjugated linoleic acid on plasma metabolite concentrations and metabolic responses to homeostatic signals in pigs.

Sixteen female cross-bred (Large White x Landrace) pigs (initial weight 65 kg) with venous catheters were randomly allocated to four treatment groups in a factorial design. The respective factors were dietary fat (25 or 100 g/kg) and dietary conjugated linoleic acid (CLA; 0 or 10 g CLA-55/kg). Pigs were fed every 3 h (close to ad libitum digestible energy intake) for 8 d and were bled frequently. Plasma glucose and non-esterified fatty acid (NEFA) responses to insulin and adrenaline challenges were determined on day 8. Plasma concentrations of NEFA were significantly increased (10.5 and 5.4 % for low- and high-fat diets respectively, P=0.015) throughout the experiment, suggesting that there was a possible increase in fat mobilisation. The increase in lipolysis, an indicator of ss-adrenergic stimulated lipolysis, was also evident in the NEFA response to adrenaline. However, the increase in plasma triacylglycerol (11.0 and 7.1 % for low- and high-fat diets respectively, P=0.008) indicated that CLA could have reduced fat accretion via decreased adipose tissue triacylglycerol synthesis from preformed fatty acids, possibly through reduced lipoprotein lipase activity. Plasma glucose, the primary substrate for de novo lipid synthesis, and plasma insulin levels were unaffected by dietary CLA suggesting that de novo lipid synthesis was largely unaffected (P=0.24 and P=0.30 respectively). In addition, the dietary CLA had no effect upon the ability of insulin to stimulate glucose removal.

Analysis of Variance↗
PubMed2004

Isomer-specific effects of conjugated linoleic acid on lipid peroxidation in humans: regulation by alpha-tocopherol and cyclo-oxygenase-2 inhibitor.

We have found previously that supplementation with conjugated linoleic acid (CLA) induces lipid peroxidation and inflammation in humans as indicated by an increase of 8-iso-prostaglandin F2alpha (PGF2alpha) and 15-keto-dihydro-PGF2alpha respectively. The present study was undertaken firstly to study the regulatory mechanisms behind these effects, and secondly to see if these effects are specific to different isomers of CLA. Sixty healthy men and women, divided into six groups, were given a cyclo-oxygenase (COX)-2 inhibitor (rofecoxib; 12 mg/day), alpha-tocopherol (200 mg/day) or neither treatment (control group) over a period of 6 weeks. During the last 4 weeks, three groups were given a CLA preparation (3.5 g/day) mainly containing the isomers cis-9, trans-11 and trans-10, cis-12 (CLA mix), and the three other groups a CLA preparation mainly containing the isomer trans-10, cis-12 (CLA 1012; 4.0 g/day). Treatment with alpha-tocopherol or COX-2 inhibitor did not alter the basal urinary levels of either 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha. Both CLA preparations induced an increase in 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha in the urine, with a larger increase being found in the CLA 1012 group. Treatment with the COX-2 inhibitor suppressed the increase in urinary 15-keto-dihydro-PGF2alpha in the CLA 1012 group, but not in the CLA mix group. Neither the COX-2 inhibitor nor alpha-tocopherol had any effect on 8-iso-PGF2alpha levels after supplementation with CLA. The CLA-induced production of PGF2alpha metabolites is probably partially mediated by COX-2. Levels of the induced lipid peroxidation may be dependent on the isomeric property of CLA.

Adult↗
PubMed1970

The enzymic conversion of linoleic acid hydroperoxide by flax-seed hydroperoxide isomerase.

1. The mode of action of flax-seed hydroperoxide isomerase was studied in vitro by using as substrates linoleic acid hydroperoxides formed by soya-bean lipoxygenase. 2. The enzyme converts only 13-hydroperoxyoctadeca-cis-9-trans-11-dienoic acid, whereas the 9-hydroperoxy isomer does not react. 3. The isomerization product was identified by chemical and spectroscopic methods as 13-hydroxy-12-oxo-octadec-cis-9-enoic acid. 4. 12,13-Epoxyoleic acid isomers do not act as intermediates in the isomerization reaction. 5. Suggestions for a functional relationship between hydroperoxide isomerase and lipoxygenase are discussed.

Ethers, Cyclic↗
PubMed2004

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.

Administration, Oral↗
PubMed2003

trans-10, cis-12 conjugated linoleic acid reduces insulin-like growth factor-II secretion in HT-29 human colon cancer cells.

We previously demonstrated that a mixture of conjugated linoleic acid (CLA) isomers decreases colon cancer incidence in rats treated with 1,2-dimethylhydrazine. Our in vitro studies have also shown that CLA inhibits the growth of HT-29 cells, a human colon cancer cell line. When we compared the individual potencies of the two main isomers found in the mixture of CLA isomers (e.g., cis-9, trans-11 [c9t11] and trans-10, cis-12 [t10c12]), t10c12 CLA decreased viable cell numbers in a dose-dependent manner. By contrast, c9t11 CLA had no effect. Therefore, the present study examined whether the decreased cell growth is related to changes in secretion of insulin-like growth factor (IGF)-II and/or IGF-binding proteins (IGFBPs) that have been shown to regulate HT-29 cell proliferation. Cells were incubated in serum-free medium with various concentrations of the individual CLA isomers, and immunoblot analysis of 24-hour, serum-free, conditioned media using a monoclonal anti-IGF-II antibody was performed. HT-29 cells secreted both mature 7,500 apparent molecular weight (M(r)) and higher-M(r) forms of IGF-II. t10c12 CLA decreased the levels of the higher-M(r) and the mature form of IGF-II in a dose-dependent manner, whereas c9t11 CLA had no effect. Ligand blot analysis of conditioned medium using (125)I-IGF-II revealed that the production of IGFBP-2 and IGFBP-4 was also decreased by t10c12 CLA, whereas c9t11 CLA had no effect. Exogenous IGF-II abrogated the growth inhibition induced by t10c12 CLA. These results indicate that inhibition of HT-29 cell growth by t10c12 CLA may be mediated by decreasing IGF-II secretion in these cells.

Cell Division↗
PubMed2000

Conjugated linoleic acid persistently increases total energy expenditure in AKR/J mice without increasing uncoupling protein gene expression.

AKR/J mice fed a high fat diet were treated with a 1% (1 g/100 g) admixture of conjugated linoleic acids (CLA) for 5 wk and compared with control mice. Body weights, energy intakes and energy expenditure (EE) determined by indirect calorimetry were measured weekly. CLA treatment reduced adipose depot weights by approximately 50% but had no significant effects on either body weight or energy intake. CLA increased EE persistently by an average of 7.7% throughout the 5-wk experiment. This greater EE, despite no difference in energy intake, was sufficient to account for the lower body fat stores in the CLA-treated mice. De novo fatty acid biosynthesis in adipose tissue, measured by incorporation of deuterium-labeled water, was not decreased by CLA treatment and therefore did not explain the lower adipose lipid in these mice. Expression of uncoupling protein (UCP) in skeletal muscle, white adipose tissue and kidney was not affected by CLA treatment. In brown adipose tissue, UCP1 expression was not affected by CLA treatment. However, UCP2 expression, although quite low, was significantly greater in CLA-fed mice. We conclude that CLA acts to reduce body fat stores by chronically increasing metabolic rate. This effect on metabolic rate is likely not due to increased UCP gene expression. Furthermore, the reduced body fat is not due to decreased de novo fatty acid synthesis in white adipose tissue.

Adipose Tissue↗
PubMed1999

Effect of dietary conjugated linoleic acid on the quality characteristics of chicken eggs during refrigerated storage.

Twenty-four, 79-wk-old White Leghorn hens were assigned randomly to three diets containing 0, 2.5, or 5.0% conjugated linoleic acid (CLA). The diets were fed for 4 wk to determine the effect of dietary CLA on quality characteristics of eggs. Eggs were collected daily and stored at 4 C for 1, 7, 21, or 49 d. At the designated times, the eggs were processed to evaluate water content, fatty acid composition, color, proportions and pH of yolk and albumen. Firmness of yolk after the eggs were hard-cooked was also determined. The proportions of myristic, palmitic, stearic, CLA (9-cis, 11-trans CLA and 10-trans, 12-cis CLA isomers), and unidentified fatty acids in egg yolk lipids were increased as dietary CLA increased, but those of palmitoleic, oleic, linoleic, linolenic, arachidonic, and docosahexaenoic acid were decreased. Duration of refrigeration increased the proportion of egg yolk but decreased the contents of albumen and yolk lipids after 21 d or longer of storage. Egg yolk pH increased as refrigeration time increased, regardless of dietary treatment, but the increase was greater in the eggs produced by hens fed the CLA diets. Albumen pH increased significantly after 7 d of storage but remained unchanged until 21 d and then decreased by 49 d. Dietary CLA had no effect on the pH of albumen until 49 d of storage. After 49 d storage, egg albumen pH from hens fed CLA diets was lower than that of albumen from hens fed the control diet. Yolk color was not influenced by the dietary CLA and storage, but the egg yolk surface from hens fed CLA diets sometimes had relatively dark color with light spots. Dietary CLA and storage of CLA eggs increased the firmness of hard-cooked egg yolk. The texture of yolks from hard-cooked CLA eggs was rubbery and elastic, and the yolks were more difficult to break using an Instron. It was speculated that the quality changes of CLA eggs were related to the increase of yolk water content, the movement of ions between yolk and albumen through yolk membrane, and the changes of egg yolk pH during storage.

Animal Feed↗
PubMed2001

Influence of conjugated linoleic acid on body composition and target gene expression in peroxisome proliferator-activated receptor alpha-null mice.

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 proliferator-activated 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.

Animals↗
PubMed2005

Effects of conjugated linoleic acids on growth performance, serum lysozyme activity, lymphocyte proliferation, and antibody production in broiler chicks.

This study was conducted to investigate the effect of dietary conjugated linoleic acids (CLA) on growth performance and immune responses in broiler chicks. A total of 240 day-old Arbor Acre male broiler chicks were randomly allotted into four dietary treatments with different inclusion levels of CLA (0, 2.5, 5.0 or 10.0 g/kg) for six weeks. Growth performance, peripheral blood lymphocyte (PBL) proliferation, lysozyme activity, phagocytic activity (carbon clearance) and serum antibody titers against Newcastle disease virus (NDV) vaccine were examined. There were no significant differences in growth performance among treatments (p > 0.05). Chicks fed CLA diets produced more lysozyme activity in serum than the control group at 2 and 6 weeks of age (p < 0.05). Dietary CLA enhanced the PBL proliferation in response to concanavalin A (ConA) at the age of 42 d (p < 0.05). Phagocytic ability was also affected by dietary CLA and chicks fed CLA diets had faster carbon clearance rate (p < 0.05), but antibody titers to NDV was not influenced by dietary CLA. The results of the study suggested that dietary CLA could enhance innate and cellular immune response in broiler chicks, and not affect the growth performance.

Animal Feed↗
PubMed2004

Effect of conjugated linoleic acid on body composition and plasma lipids in humans: an overview of the literature.

Studies in mice have indicated that feeding diets containing 0.5-1% conjugated linoleic acid (CLA) considerably reduces body fat. These findings have attracted much interest because of the potential use of CLA as a tool to promote weight loss in humans. Several CLA studies in humans have now been published, and the objective of the present review was to give an overview of these experiments. Most of the studies were done in free-living subjects and were not strictly controlled for nutrient and energy intakes. None of the studies found a significant reduction in body weight, and only 2 studies showed a significant but relatively small body fat-lowering effect. Some studies suggested that CLA may have a tendency to increase lean body mass. Furthermore, there are indications from animal studies that CLA may have effects on plasma lipids. However, only one study in humans showed a significant HDL-cholesterol-lowering effect of CLA; in all the other studies, there were no significant effects on plasma total, LDL-, and HDL-cholesterol concentrations or on plasma triacylglycerol concentrations. Thus, the results of the studies in humans indicate that the effect of CLA on body fat is considerably less than that anticipated from mice studies and that CLA has no major effect on plasma lipids.

Adipose Tissue↗
PubMed1999

Biotechnology for the production of nutraceuticals enriched in conjugated linoleic acid: I. Uniresponse kinetics of the hydrolysis of corn oil by a pseudomonas sp. lipase immobilized in a hollow fiber reactor

The kinetics of the hydrolysis of corn oil in the presence of a lipase from Pseudomonas sp. immobilized within the walls of a hollow fiber reactor can be modeled in terms of a three-parameter rate expression. This rate expression consists of the product of a two-parameter rate expression for the hydrolysis reaction itself (which is of the general Michaelis-Menten form) and a first-order rate expression for deactivation of the enzyme. Optimum operating conditions correspond to 30 degrees C and buffer pH values of 7.0 during both immobilization of the enzyme and the hydrolysis reaction. Under these conditions, the total fatty acid concentration in the effluent oil stream for a fluid residence time of 4 h is approximately 1.6 M. This concentration corresponds to hydrolysis of approximately 50% of the glyceride bonds present in the feedstock corn oil. The fatty acid of primary interest in the effluent stream is linoleic acid. Copyright 1999 John Wiley & Sons, Inc.

Journal Article↗