trans-10-cis-12-conjugated-linoleic-acid and Body-Weight

Conjugated linoleic acids (CLA) have been demonstrated to be a potent inhibitor of milk fat synthesis in ruminants, but effects on carcass composition and organ weight are unknown. Our objectives in this experiment were to determine the dose response of ruminally protected CLA on the performance, organ weight, and fatty acid (FA) composition of early lactation dairy ewes. Twenty-four multiparous dairy ewes were fed a basal diet for 10 wk that was supplemented with a lipid-encapsulated CLA at 1 of 3 levels: no CLA (control, CON), low CLA (L-CLA), or high CLA (H-CLA) to supply 0, 1.5, or 3.8 g/d, respectively, of both trans-10, cis-12 and cis-9, trans-11 CLA. Dry matter intake was not affected (P > 0.05) by dietary treatment. Ewes fed H-CLA had a 13% higher milk yield compared with those receiving either CON or L-CLA. Compared with CON, milk fat yield (g/d) was 14 and 24% lower in ewes fed L-CLA or H-CLA, respectively. Supplementing ewes with CLA did not affect carcass or organ weights, carcass composition, or organ FA content. Compared with ewes receiving the CON diet, CLA supplementation had little effect on the FA composition of the Longissimus dorsi, although cis-9, trans-11 and trans-10, cis-12 CLA were increased in ewes receiving H-CLA. The current findings are consistent with the view that the energy spared by the CLA reduction in milk fat content was mainly partitioned to milk yield and there was no evidence of organ hypertrophy or liver steatosis.

Topics: Adipose Tissue; Animals; Body Fat Distribution; Body Weight; Dairying; Diet; Dietary Fats; Fatty Acids; Female; Heart; Isomerism; Lactation; Linoleic Acids, Conjugated; Lung; Mammary Glands, Animal; Milk; Muscle, Skeletal; Myocardium; Organ Size; Sheep, Domestic; Time Factors

Diets containing high n-3 polyunsaturated fatty acids (PUFA) decrease inflammation and the incidence of chronic diseases including cardiovascular disease and nonalcoholic fatty liver disease while trans-fatty acids (TFA) intake increases the incidence of these conditions. Some health benefits of n-3 PUFA are mediated through the impact of their oxygenated metabolites, i.e. oxylipins. The TFA, trans-10, cis-12-conjugated linoleic acid (CLA; 18:2n-6) is associated with adipose tissue (AT) inflammation, oxidative stress, and wasting. We examined the impact of a 4-week feeding of 0, 0.5, and 1.5% docosahexaenoic acid (DHA; 22:6n-3) in the presence and absence of 0.5% CLA on AT oxylipin profiles in female C57BL/6N mice. Esterified oxylipins in AT derived from linoleic acid (LNA), alpha-linolenic acid (ALA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), DHA, and putative from CLA were quantified. CLA containing diets reduced AT mass by ~62%. Compared with the control diet, the DHA diet elevated concentrations of EPA-and DHA-derived alcohols and epoxides and LNA-derived alcohols, reduced ARA-derived alcohols, ketones, epoxides, and 6-keto-prostaglandin (PG) F

Topics: Adipose Tissue; Animals; Body Weight; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Eating; Female; Linoleic Acids, Conjugated; Mice; Oxylipins; Uterus

The acute oral toxicity of a trans-10 C18:1-rich milk fat (T10, 20% of total FA), and a trans-11 C18:1+cis-9 trans-11 C18:2-rich milk fat (T11-CLA, 14% and 4.8% of total FA, respectively) was studied in rats receiving a single oral dose of 2000 mg/kg body weight (BW). T10 and T11-CLA milk fats were well tolerated; no adverse effects or mortality were observed during the 2-week observation period. Two weeks following a single oral dose of 2000 mg/kg BW of T10 and T11-CLA milk fats there were no changes in haematological and serum chemistry parameters (excepting plasma lipid) organ weights, gross pathology or histopathology. In rats treated with T10 milk fat a significant increase of triglycerides was observed. In contrast, in rats treated with T11-CLA milk fat significantly decreased triglycerides were detected. It was concluded that dairy fats rich in T10 and T11-CLA have a low order of acute toxicity, the oral lethal dose (DL50) for male and female rats are in excess of 2000 mg/kg BW. Our results suggest that the T10 milk fat treatment tended to increase triglycerides concentrations, whereas the T11-CLA milk fat treatment tended to reduce it.

Topics: Animals; Body Weight; Chemistry, Clinical; Dietary Supplements; Eating; Fatty Acids; Female; Food Additives; Hematologic Tests; Linoleic Acids, Conjugated; Longevity; Male; Milk; Oleic Acids; Rats; Rats, Wistar; Sheep; Toxicity Tests, Acute

Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are found in 35 and 30 % of US adults, respectively. Trans-10, cis-12-conjugated linoleic acid (CLA) has been found to cause both these disorders in several animal models. We hypothesised that IR and NAFLD caused by CLA result from n-3 fatty acid deficiency. Pathogen-free C57BL/6N female mice (aged 8 weeks; n 10) were fed either a control diet or diets containing trans-10, cis-12-CLA (0.5 %) or CLA+flaxseed oil (FSO) (0.5 %+0.5 %) for 8 weeks. Weights of livers, concentration of circulating insulin, values of homeostatic model 1 (HOMA1) for IR and HOMA1 for beta cell function were higher by 160, 636, 985 and 968 % in the CLA group compared with those in the control group. FSO decreased fasting glucose by 20 % and liver weights by 37 % compared with those in the CLA group; it maintained circulating insulin, HOMA1-IR and HOMA1 for beta cell function at levels found in the control group. CLA supplementation decreased n-6 and n-3 wt% concentrations of liver lipids by 57 and 73 % and increased the n-6:n-3 ratio by 58 % compared with corresponding values in the control group. FSO increased n-6 and n-3 PUFA in liver lipids by 33 and 342 % and decreased the n-6:n-3 ratio by 70 % compared with corresponding values in the CLA group. The present results suggest that some adverse effects of CLA may be due to n-3 PUFA deficiency and that these can be corrected by a concomitant increase in the intake of alpha-linolenic acid, 18 : 3n-3.

Topics: Animal Nutritional Physiological Phenomena; Animals; Blood Glucose; Body Weight; Disease Models, Animal; Eating; Fatty Liver; Female; Insulin; Insulin Resistance; Linoleic Acids, Conjugated; Linseed Oil; Lipid Metabolism; Lipids; Liver; Mice; Mice, Inbred C57BL; Organ Size

Conjugated linoleic acid (CLA) has shown a number of biologically beneficial effects, including prevention of obesity. The purpose of this study was to test effects of dietary supplementation of 0.5% trans-10,cis-12 CLA in a high fat diet in neuronal basic helix-loop-helix 2 knock-out animals (N2KO), which is a unique animal model representing adult-onset inactivity-related obesity. Eight wild-type (WT) and eight N2KO female mice were fed either 0.5% trans-10,cis-12 CLA-containing diet or control diet (with 20% soybean oil diet) for 12 weeks. Body weights, food intake, adipose tissue weights, body compositions, and blood parameters were analyzed. Overall, N2KO animals had greater body weights, food intake, adipose tissue weights, and body fat compared to WT animals. CLA supplementation decreased overall body weights and total fat, and the effect of dietary CLA on adipose tissue reduction was greater in N2KO than in WT mice. Serum leptin and triglyceride levels were reduced by CLA in both N2KO and WT animals compared to control animals, while there was no effect by CLA on serum cholesterol. The effect of CLA to lower fat mass, increase lean body mass, and lower serum leptin and triglycerides in sedentary mice supports the possibility of using CLA to prevent or alleviate ailments associated with obesity.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol; Dietary Supplements; Energy Intake; Female; Leptin; Linoleic Acids, Conjugated; Mice; Mice, Knockout; Mice, Obese; Obesity; Triglycerides

It has been proposed that young animals and subjects are more responsive to conjugated linoleic acid (CLA) than the adults. Nevertheless, there is very little information concerning the effectiveness of CLA in adult animals. In the present study we aimed to explore the effects of trans-10, cis-12-CLA on body fat accumulation in adult hamsters, as well as on some of the molecular mechanisms described in young animals as responsible for the CLA body fat-lowering effect, such as lipogenesis, lipoprotein lipase (LPL)-mediated fat uptake and thermogenesis. The experiment was conducted with sixteen adult male Syrian Golden hamsters (aged 8 months) fed a high-fat diet supplemented or not with 0.5 % trans-10, cis-12-CLA for 6 weeks. Acetyl-CoA carboxylase (ACX), fatty acid synthase (FAS), LPL, PPARgamma, sterol regulatory element-binding protein (SREBP)-1a and SREBP-1c expressions were assessed in subcutaneous and perirenal adipose tissues by real-time RT-PCR. Total and heparin-releasable LPL activities were determined in subcutaneous adipose tissue by fluorimetry and FAS activity by spectrophotometry. Uncoupling protein-1 (UCP1) expression in interscapular brown adipose tissue was assessed by Western blot. Hamsters fed the trans-10, cis-12-CLA diet showed a significant reduction in subcutaneous adipose tissue. No changes were observed in the expression of ACX, FAS, LPL, SREBP-1a, SREBP-1c and PPARgamma, nor in total and heparin-releasable LPL and FAS activities. Trans-10, cis-12-CLA induced a significant increase in the amount of UCP1. These results suggest a low responsiveness to trans-10, cis-12-CLA in adults, lower than that in young hamsters. One of the reasons explaining this difference is the lack of effect on LPL.

Topics: Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Body Weight; Cricetinae; Eating; Gene Expression Regulation, Enzymologic; Ion Channels; Linoleic Acids, Conjugated; Lipogenesis; Male; Mesocricetus; Mitochondrial Proteins; Reverse Transcriptase Polymerase Chain Reaction; Subcutaneous Fat; Transcription Factors; Uncoupling Protein 1

It is known that conjugated linoleic acid (CLA) feeding decreases body adiposity but the mechanisms involved are not clear. The aim of this study was to analyse whether alterations in uncoupling protein (UCP) expression in white and brown adipose tissues (WAT and BAT, respectively) and in skeletal muscle may be responsible for the effect of trans-10, cis-12 CLA on the size of body fat depots in hamsters. Animals were divided into three groups and fed an atherogenic diet with different amounts of trans-10, cis-12 CLA (0 control, 0.5, or 1 g/100 g diet) for 6 weeks. CLA feeding reduced adipose depot weights, but had no effect on body weight. Leptin mRNA expression decreased in both subcutaneous and perirenal WAT depots, in accordance with lower adiposity, whereas resistin mRNA expression was not changed. Animals fed CLA had lower UCP1 mRNA levels in BAT (both doses of CLA) and in perirenal WAT (the low dose), and lower UCP3 mRNA levels in subcutaneous WAT (the high dose). UCP2 mRNA expression in WAT was not significantly affected by CLA feeding. Animals fed the high dose of CLA showed increased UCP3 and carnitine palmitoyl transferase-I (CPT-I) mRNA expression levels in skeletal muscle. In summary, induction of UCP1 or UCP2 in WAT and BAT is not likely to be responsible for the fat-reduction action of CLA, but the increased expression of UCP3 in skeletal muscle, together with a higher expression of CPT-I, may explain the previously reported effects of dietary CLA in lowering adiposity and increasing fatty acid oxidation by skeletal muscle.

Topics: Adipose Tissue; Animals; Blotting, Northern; Body Weight; Cricetinae; Diet, Atherogenic; Dietary Supplements; Dose-Response Relationship, Drug; Eating; Gene Expression Regulation; Ion Channels; Leptin; Linoleic Acids, Conjugated; Male; Mesocricetus; Mitochondrial Proteins; Muscle, Skeletal; Resistin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Uncoupling Protein 1

Conjugated linoleic acid (CLA) has received great attention in recent years because of its pleiotropic biological activities, but considerably fewer studies have been published addressing its role in serum lipids and atherosclerosis compared to other topics covered.. The aim of the present study was to assess the effects of the trans-10,cis-12 isomer of CLA on cholesterolaemia and on several metabolic pathways involved in cholesterol metabolism in hamsters.. Animals were fed atherogenic diets supplemented with 0.5% linoleic acid, 0.5% trans-10,cis-12 CLA or 1.0% trans-10,cis-12 CLA, for 6 weeks. Serum lipoproteins were separated by FPLC. Cholesterol in serum and liver, as well as triacylglycerols and phospholipids in liver were assessed by spectrophotometry. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR), acyl-coenzyme A:cholesterol acyltransferase (ACAT) and cholesteryl ester hydrolase (CEH) activities were measured by radiometry, and LDL receptors were determined by Western blot.. trans-10,cis-12 CLA feeding did not modify food intake nor final body weight. Although serum total cholesterol remained unchanged, when cholesterol fractions were analyzed a significant decrease in VLDL-cholesterol was observed in CLA-fed animals, without changes in HDL-cholesterol or LDL-cholesterol. trans-10,cis-12 CLA decreased cholesterol ester content and increased free cholesterol in liver. The activity of HMGCoAR was not modified. In contrast, ACAT activity was reduced by both CLA doses and CEH was increased by the high CLA dose. LDL receptors were significantly reduced by trans-10,cis-12 feeding when expressed as arbitrary units per mg of protein, however, the total receptor mass remained unchanged.. These results suggest that, under the present experimental conditions, trans-10,cis-12 CLA feeding reduces cholesterol esterification in liver and decreases the minority serum VLDL-cholesterol fraction, but it does not show a hypocholesterolaemic effect. A dose-response effect was not observed.

Topics: Animals; Blotting, Western; Body Weight; Cholesterol; Chromatography, Liquid; Cricetinae; Diet, Atherogenic; Dose-Response Relationship, Drug; Eating; Hydroxymethylglutaryl CoA Reductases; Hypercholesterolemia; Linoleic Acids, Conjugated; Lipid Metabolism; Liver; Male; Mesocricetus; Phospholipids; Radiometry; Spectrophotometry; Sterol Esterase; Sterol O-Acyltransferase; Triglycerides

Numerous studies have demonstrated that conjugated linoleic acid (CLA) modulates body composition, reducing body fat accumulation in various mammalian species. However, very few studies have been carried out to assess the effect of CLA on previously stored body fat. The aim of the present work was to analyse the effectiveness of trans-10,cis-12 CLA in improving alterations produced by high-fat feeding in body fat and serum parameters when it was included in an energy-restricted diet. For this purpose male Syrian Golden hamsters were fed on high-fat diet for 7 weeks in order to increase their body fat content, and a further 25% energy-restricted diet supplemented or not with 0.5% trans-10,cis-12 CLA for 3 weeks. Adipose tissues, liver and gastrocnemious muscles were dissected and weighed. Adipocyte diameter and number were assessed in epididymal adipose tissue. Total cholesterol, triacylglycerols, non-esterified fatty acids and glucose were measured in serum. Three weeks of energy restriction resulted in a reduction in body weight and white adipose tissue size in all anatomical locations, without changes in liver and gastrocnemious muscle weights. Epididymal adipocyte size was reduced, but total adipocyte number remained unchanged. Serum cholesterol, triacylglycerols and glucose were significantly reduced. No differences were observed between the restricted groups (control and CLA supplemented). In conclusion, under our experimental conditions, the addition of trans-10,cis-12 CLA to the diet does not increase the benefits produced by energy restriction.

Topics: Adipose Tissue; Adiposity; Animals; Body Weight; Cholesterol; Cricetinae; Energy Intake; Fatty Acids, Nonesterified; Linoleic Acids, Conjugated; Male

The aim of the present work was to determine whether t-10, c-12 conjugated linoleic acid (CLA) feeding was able to reduce body fat accumulation and improve the serum lipid profile in adult hamsters fed an atherogenic diet, in order to compare these effects with those observed in young growing hamsters. Young and adult hamsters were fed semi-purified atherogenic diets supplemented with 0.5 % linoleic acid or 0.5% t-10, c-12 CLA for 6 weeks. Body weight and food intake were measured every two days. Adipose tissue from different anatomical locations, liver and gastrocnemious muscle were dissected and weighed. Cholesterol, triacylglycerols, non-esterified fatty acids and proteins were determined spectrophotometrically and water content by gravimetry. In young hamsters, no significant differences were found in food intake, final body weight and gastrocnemious muscle weight. White adipose tissue weights were reduced, liver weight was increased and cholesterol and triacyl-glycerols in both serum and liver were reduced. In adult hamsters, CLA feeding decreased food intake and adipose tissue weights. No changes were observed in other parameters. The present study demonstrates that age has an influence in hamster responsiveness to t-10, c-12 CLA because, although when this isomer is added to an atherogenic diet it reduces body fat accumulation in both young and adults hamsters, the lessening of the effects on serum lipids brought about by atherogenic feeding is only observed in young animals. Moreover, it is clear that liver is a target for CLA in young but not in adult hamsters.

Topics: Adipose Tissue; Aging; Animals; Body Weight; Cholesterol; Cricetinae; Diet, Atherogenic; Eating; Energy Intake; Fatty Acids, Nonesterified; Linoleic Acids, Conjugated; Lipids; Liver; Male; Mesocricetus; Triglycerides

Conjugated linoleic acids (CLA) affect atherogenesis, but mechanisms are not well understood. We explored how two isomers of CLA, cis9, trans11-CLA and trans10, cis12-CLA, affected lipid and glucose metabolism, as well as hepatic protein expression, in apolipoprotein E knockout mice. After 12 wk of intervention, plasma triglyceride, NEFA, and glucose concentrations were significantly higher in the trans10, cis12-CLA group, whereas plasma triglyceride, NEFA, glucose, and insulin concentrations were significantly lower in the cis9, trans11-CLA group, compared with control mice consuming linoleic acid. Proteomics identified significant up- or down-regulation of 113 liver cytosolic proteins by either CLA isomer. Principal component analysis revealed that the treatment effect of cis9, trans11-CLA was mainly explained by the up-regulation of different posttranslational forms of heat shock protein 70 kD. In contrast, the treatment effect of trans10, cis12-CLA was mainly explained by up-regulation of key enzymes in the gluconeogenic, beta-oxidation, and ketogenesic pathways. Correlation analysis again emphasized the divergent effects of both CLA isomers on different pathways, but also revealed a linkage between insulin resistance and increased levels of hepatic serotransferrin. Thus, our systems biology approach provided novel insights into the mechanisms by which individual CLA isomers differentially affect pathways related to atherogenesis, such as insulin resistance and inflammation.

Topics: Animal Feed; Animals; Apolipoproteins E; Atherosclerosis; Blood Glucose; Blotting, Western; Body Composition; Body Weight; Cytosol; Diet; Fatty Acids; Genetic Linkage; Glucose; HSP70 Heat-Shock Proteins; Inflammation; Insulin; Insulin Resistance; Linoleic Acid; Linoleic Acids, Conjugated; Liver; Male; Mice; Mice, Knockout; Oxygen; Perfusion; Principal Component Analysis; Proteomics; Systems Biology; Triglycerides