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.     

Conjugated linoleic acid (CLA), body fat, and apoptosis

OBJECTIVE: The objective of the study was to determine if consumption of conjugated linoleic acid (CLA) by mice could induce apoptosis in adipose tissue. Other objectives were to determine the influence of feeding mice CLA for < or =2 weeks on body fat, energy expenditure, and feed intake. RESEARCH METHODS AND PROCEDURES: A mixture of CLA isomers (predominantly c9,t11 and t10,c12) was included in the AIN-93G diet at 0, 1, and 2%, and fed to mice for 12 days (Trial 1), or was included at 2% and fed to mice for 0, 5, and 14 days (Trial 2). Feed intake was measured daily and energy expenditure was determined by direct calorimetry on day 9 in Trial 1. Retroperitoneal fat pads were analyzed for apoptosis by determination of DNA fragmentation. RESULTS: Dietary CLA reduced feed intake by 10% to 12% (p < 0.01), but either did not influence or did not increase energy expenditure as indicated by heat loss. Body weight was not influenced by consumption of CLA in Trial 1 but was increased (p < 0.01) by CLA in Trial 2. Weights of retroperitoneal, epididymal, and brown adipose tissues were lower (p < 0.01) in animals fed CLA, although liver weight was increased (p < 0.10; Trial 1) or not changed (Trial 2). Analysis of retroperitoneal fat pad DNA from both trials indicated that apoptosis was increased (p < 0.01) by CLA consumption. DISCUSSION: These results are interpreted to indicate that CLA consumption causes apoptosis in white adipose tissue. This effect occurs within 5 days of consuming a diet that contains CLA.     

Diet supplementation with the cis-9,trans-11 conjugated linoleic acid isomer affects the size of adipocytes in Wistar rats

Previous reports have demonstrated that conjugated linoleic acid (CLA) acts on body fat accumulation in a variety of animal models. The aim of the present study was to investigate the effect of cis (c)-9,trans (t)-11 and t10,c12 CLA isomers on the number and size of adipocytes from the inguinal and retroperitoneal fats in Wistar male rats. A 5.1% palm oil–based diet was supplemented with CLA isomers as follows: 0.6% of c9,t11, 0.6% of t10,c12, 1.3% of c9,t11 and t10,c12 isomers in mixture, and a control nonsupplemented group for comparative purposes. Fat tissues were prepared on microscope slides for histologic examination using an image-analysis software to count the number of adipocytes and measure cell sizes. The results showed that CLA isomers did not affect (P > .05) either final body and fat depot weights or serum lipids (with the exception of triacylglycerols) and adipocytokines (leptin and adiponectin). Animals fed the c9,t11 CLA isomer diet showed larger adipocytes when compared to other groups. Independently of the CLA dietary treatment, retroperitoneal fat showed larger adipocytes (3319 μm²) and therefore a smaller number of adipocytes per unit of area, compared to inguinal fat (3055 μm²). Taken together, the data suggest that a palm oil–based diet supplemented with the c9,t11 CLA isomer in Wistar rats, in contrast to the t10,c12 isomer and the mixture of both isomers, increases adipocyte dimensions in inguinal and retroperitoneal fat depots, while having a minor effect in serum lipids and adipocytokines.     

The trans-10,cis-12 isomer of conjugated linoleic acid reduces hepatic triacylglycerol content without affecting lipogenic enzymes in hamsters

Conjugated linoleic acid (CLA) refers to the positional and geometric dienoic isomers of linoleic acid. The dietary intake of CLA has been associated with changes in lipid metabolism. The aim of the present work was to assess the effects of the two main isomers of CLA on sterol regulatory element binding protein (SREBP)-1a and SREBP-1c mRNA levels, as well as on mRNA levels and the activities of several lipogenic enzymes in liver. For this purpose hamsters were fed an atherogenic diet supplemented with 5 g linoleic acid, cis-9,trans-11 or trans-10,cis-12 CLA/kg diet for 6 weeks. The trans-10,cis-12 isomer intake produced significantly greater liver weight, but also significantly decreased liver fat accumulation. No changes in mRNA levels of SREBP-1a, SREBP-1c and lipogenic enzymes, or in the activities of these enzymes, were observed. There was no effect of feeding cis-9,trans-11 CLA. These results suggest that increased fat accumulation in liver does not occur on the basis of liver enlargement produced by feeding the trans-10,cis-12 isomer of CLA in hamsters. The reduction in hepatic triacylglycerol content induced by this isomer was not attributable to changes in lipogenesis.     

Effect of dietary conjugated linoleic acid on body composition and energy balance in broiler chickens

The effect of dietary conjugated linoleic acid (CLA) on body composition and energy metabolism was investigated in broiler chickens. Male broiler chicks were assigned to receive either a control diet (1 % sunflower oil) or a diet containing CLA (1 % of a 1:1 mixture of trans-10, cis-12 and cis-9, trans-11 isomers of octadecadienoic acid). The diets were fed ad libitum for 3 weeks and there were eight replicates per diet, each replicate including four chickens so that each treatment had thirty-two animals. The proportion of body fat was lower in the control group than in the CLA group. No significant differences as to the proportions of body water, ash and protein were observed. Feed and energy intake were significantly lower in CLA-fed birds. The percentage of ingested energy lost in excreta was higher after CLA feeding and heat expenditure as a percentage of ingested energy was lower in the CLA-fed group. The CLA-fed group showed a higher percentage of SFA and lower percentages of MUFA and PUFA in carcass fat. It is concluded that CLA stimulated de novo fatty acid synthesis and lowered desaturase activity.     

Effects of conjugated linoleic acid (CLA) isomers on lipid levels and peroxisome proliferation in the hamster

Effects of the conjugated linoleic acid (CLA) isomers cis-9, trans-11 (c9,t11 CLA) and trans-10, cis-12 (t10,c12 CLA) on lipid metabolism and markers of peroxisome proliferation were investigated in hamsters fed on purified diets containing 30% energy as fat and 0.1 g cholesterol/kg for 8 weeks. Four groups (n 32 each) received diets without CLA (control), with a mixture of equal amounts of c9,t11 and t10,c12 CLA (CLA mix), with c9,t11 CLA, and with t10,c12 CLA. The total amount of CLA isomers was 1.5% energy of 6.6g/ kg diet. CLA was incorporated into glycerides and exchanged for linoleic acid in the diet. Compared with the control, the CLA mix and t10,c12 CLA decreased fasting values of LDL- (21 and 18% respectively) and HDL-cholesterol (8 and 11%), increased VLDL-triacylglycerol (80 and 61%, and decreased epididymal fat pad weights (9 and 16%), whereas c9,t11 CLA had no significant effects. All CLA preparations increased liver weight, but not liver lipids. However, the increase in liver weight was much less in the c9,t11 CLA group (8%) than in the other two groups (25%) and might have been caused by the small amount of t10,c12 CLA present in the c9,t11 CLA preparation. Liver histology revealed that increased weight was due to hypertrophy. Markers of peroxisome proliferation, such as cyanide-insensitive palmitoyl CoA oxidase (EC 1.3.3.6) and carnitine acetyl transferase (EC 2.3.1.7) activities, were not increased by CLA. Both c9,t11 CLA and t10,c12 CLA were incorporated into phospholipids and triacylglycerols, but t10,c12 CLA only about half as much as c9,t11 CLA. In addition, linoleic acid and linolenic acid concentrations were lower in lipids of the t10,c12 CLA group compared with the c9,t11 CLA group. These data suggest that t10,c12 CLA stimulated the oxidation of all C18 polyunsaturated fatty acids. The results indicate that the t10,c12 CLA isomer, and not the so-called natural CLA isomer (c9,t11), is the active isomer affecting lipid levels in hamsters.     

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.     

Daily intake of conjugated linoleic acid-enriched yoghurts: effects on energy metabolism and adipose tissue gene expression in healthy subjects

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. The present study was designed to determine whether 14-week CLA supplementation as triacylglycerols (3.76 g) with a 50 : 50 combination of the two main isomers (35 % cis-9, trans-11 and 35 % trans-10, cis-12) added to flavoured yoghurt-like products was able to alter body composition in healthy subjects and to alter the expression of several key adipose tissue genes (PPAR gamma, lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and uncoupling protein 2 (UCP-2)). Forty-four healthy subjects were randomly assigned to consume daily either a CLA-supplemented yoghurt-like product or a placebo yoghurt for 98 d. There were no significant effects of CLA supplementation on body weight, fat mass or free fat mass. Basal energy expenditure expressed as kg free fat mass increased significantly in the CLA group (123.3 (SEM 2.5) kJ/kg free fat mass per d on day 98 v. 118.7 (SEM 2.3) kJ/kg free fat mass per d on day 0, P = 0.03). PPAR gamma mRNA gene expression increased significantly with CLA supplementation (53 (SEM 20) %, P < 0.01) and a significant reduction in mRNA levels of HSL was observed ( - 42 (SEM 7) %, P = 0.01). The levels of UCP-2 and LPL mRNA were not affected. The present results suggest that a 98 d supplementation diet with a 50 : 50 mixture of the two CLA isomers cis-9, trans-11 and trans-10, cis-12 in a dairy product was unable to alter body composition, although a significant increase in the RMR has been induced. Moreover, changes in mRNA PPAR gamma and HSL in adipose tissue were recorded.     

A CLA mixture prevents body triglyceride accumulation without affecting energy expenditure in Syrian hamsters

We examined the effects of feeding conjugated linoleic acids (CLA) to adult male hamsters on several components of energy metabolism and body composition. Hamsters (n = 54) were assigned for 6-8 wk to one of three diets: 1) a standard diet (in percentage energy: lipids, 33, carbohydrates, 49, and proteins, 18); 2) to the standard diet augmented with the 9c,11t-isomer of CLA to 1.6% of energy (R group); or 3) the standard diet augmented with the 9c,11t-isomer and the 10t,12c-CLA isomer to 3.2 (1.6 + 1.6) % of energy (CLA mix group). (15)N uniformly labeled milk-protein was included in the diet to measure the incorporation of dietary protein into liver and muscle. Basal metabolic rate, thermogenic response to feeding and energy expenditure during spontaneous activity or during an exercise at approximately 60% of VO(2max) were measured. Carnitine palmitoyltransferase-I (CPT-I), leptin, insulin and triiodothyronine concentrations, as well as the in vivo overall adiposity changes were also determined. After 6 wk, the whole-body triglyceride content determined in vivo by NMR was significantly higher in the R group than in the control and CLA mix groups. The CLA mix group differed from the others in the lack of body triglyceride accumulation between d 21 and d 45 of the study, and the appearance of a slight insulin-resistance (homeostatic model assessment index, P < 0.05). Paradoxically, the lack of effect on whole-body lipid oxidation was associated with a greater CPT-I-specific activity in tissues of both CLA-fed groups (P < 0.05). No other major effects of CLA feeding were detected. In conclusion, CLA supplementation in hamsters did not affect adipose weight or the components of energy expenditure despite a theoretically higher capacity of red muscle to oxidize lipids. Only a CLA mixture prevented whole-body triglyceride accumulation over time.     

Effects of three different conjugated linoleic acid preparations on insulin signalling, fat oxidation and mitochondrial function in rats fed a high-fat diet

To investigate the effects of three different conjugated linoleic acid (CLA) preparations containing different ratios of CLA isomers on insulin signalling, fatty acid oxidation and mitochondrial function, Sprague-Dawley rats were fed a high-fat diet either unsupplemented or supplemented with one of three CLA preparations at 1 % of the diet for 8 weeks. The first CLA preparation contained approximately 30 % cis-9, trans-11 (c9, t11)-CLA isomer and 40 % trans-10, cis-12 (t10, c12)-CLA isomer (CLA-mix). The other two preparations were an 80:20 mix (c9, t11-CLA-mix) or a 10:90 mix of two CLA isomers (t10, c12-CLA-mix). Insulin resistance was decreased in all three supplemented groups based on the results of homeostasis model assessment and the revised quantitative insulin-sensitivity check index. The phosphorylation of insulin receptor substrate-1 on serine decreased in the livers of all three supplemented groups, while subsequent Akt phosphorylation increased only in the t10, c12-CLA-mix group. Both the c9, t11-CLA-mix and the t10, c12-CLA-mix increased the expression of hepatic adiponectin receptors R1 and 2, which are thought to enhance insulin sensitivity and fat oxidation. The c9, t11-CLA-mix increased protein and mRNA levels of PPAR alpha, acyl-CoA oxidase and uncoupling protein, which are involved in fatty acid oxidation and energy dissipation. The c9, t11-CLA-mix enhanced mitochondrial function and protection against oxidative stress by increasing the activities of cytochrome c oxidase, manganese-superoxide dismutase, glutathione peroxidase, and glutathione reductase and the level of GSH. In conclusion, all three CLA preparations reduced insulin resistance. Among them, the c9, t11-CLA-mix was the most effective based on the parameters reflecting insulin resistance and fat oxidation, and mitochondrial antioxidative enzyme activity in the liver.     

Effects of two conjugated linoleic Acid isomers on body fat mass in overweight humans

OBJECTIVE: To examine the effects of two different conjugated linoleic acid (CLA) isomers at two different intakes on body composition in overweight humans. RESEARCH METHODS AND PROCEDURES: Eighty-one middle-aged, overweight, healthy men and women participated in this bicentric, placebo-controlled, double-blind, randomized study. For 6 weeks (run-in period), all subjects consumed daily a drinkable dairy product containing 3 g of high oleic acid sunflower oil. Volunteers were then randomized over five groups receiving daily either 3 g of high oleic acid sunflower oil, 1.5 g of cis-9,trans-11 (c9t11) CLA, 3 g of c9t11 CLA, 1.5 g of trans-10,cis-12 (t10c12) CLA, or 3 g of t10c12 CLA administrated as triacylglycerol in a drinkable dairy product for 18 weeks. Percentage body fat mass and fat and lean body mass were assessed at the end of the run-in and experimental periods by DXA. Dietary intake was also recorded. RESULTS: Body fat mass changes averaged 0.1 +/- 0.9 kg (mean +/- SD) in the placebo group and -0.3 +/- 1.4, -0.8 +/- 2.1, 0.0 +/- 2.3, and -0.9 +/- 1.7 kg in the 1.5-g c9t11, 3-g c9t11, 1.5-g t10c12, and 3-g t10c12 groups, respectively. Changes among the groups were not significantly different (p = 0.444). Also, lean body mass and dietary intake were not significantly different among the treatments. DISCUSSION: A daily consumption of a drinkable dairy product containing up to 3 g of CLA isomers for 18 weeks had no statistically significant effect on body composition in overweight, middle-aged men and women.     

Conjugated linoleic acid and human health-related outcomes

Summary There has been increasing interest in health benefits of conjugated linoleic acid (CLA) based on findings with laboratory animals. Some human studies have also suggested health benefits of CLA, but because of the mixes used these could not be readily associated with a particular isomer of CLA. A recent study examined the separate effects of near‐pure cis‐9,trans‐11 CLA (c9,t11 CLA) or trans‐10,cis‐12 CLA (t10,c12 CLA) on health‐related outcomes in healthy young males. The CLA isomers were provided in capsules and at three doses (up to about 2.5 g/day) each for 8 weeks. Both c9,t11 and t10,c12 CLA were incorporated in a dose–response fashion into blood lipids and cells. At the doses and durations used, neither isomer of CLA affected bodyweight, body mass index or body composition, insulin sensitivity, immune function or markers of inflammation. However, at the doses and durations used, c9,t11 and t10,c12 CLA had opposing effects on blood lipid concentrations. Altered dairy cow‐feeding practices were used to produce c9,t11 CLA‐rich milk and, from this ultra heat‐treated milk, cheese and butter were produced. The milk and the dairy products made from it had ninefold higher contents of c9,t11 CLA, higher contents of n‐3 fatty acids and lower contents of total fat and of saturated fatty acids. They also contained much higher contents of trans‐vaccenic acid (tVA). The modified dairy products were used in a 6‐week controlled dietary intervention study in healthy middle‐aged males. c9,t11 CLA and tVA were incorporated from dairy products into blood lipids and cells. Consumption of the CLA‐rich (and tVA‐rich) dairy products did not affect bodyweight or body mass index, insulin sensitivity or inflammatory markers. However, there were some detrimental effects on blood lipids. These effects may be due to tVA rather than to c9,t11 CLA, as they are consistent with the effects of trans fatty acids and not consistent with the effects of c9,t11 CLA identified in the earlier study with c9,t11 CLA in capsules.     

The 10trans, 12cis isomer of conjugated linoleic acid promotes energy metabolism in OLETF rats

OBJECTIVE: We investigated the effect of conjugated linoleic acid (CLA) on energy metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: In experiment 1, male OLETF rats were fed either control diet, 10% safflower oil or CLA diet, 9% safflower oil plus 1% CLA for 4 wk. In experiment 2, male OLETF rats were fed either 9c,11t-CLA diet, 9% safflower oil plus 1% 9c,11t-CLA-rich oil or 10t,12c-CLA diet, 9% safflower oil plus 1% 10t,12c-CLA-rich oil for 10 d. RESULTS: In experiment 1, after 4 wk of feeding, serum and hepatic triacylglycerol concentrations in the CLA group were decreased significantly as compared with the control group. The CLA diet increased oxygen consumption and energy expenditure as compared with the control diet in OLETF rats. In experiment 2, a significant reduction of serum and hepatic triacylglycerol concentrations was seen in the 10t,12c-CLA group as opposed to the 9c,11t-CLA group. Oxygen consumption and energy expenditure were significantly higher in the 10t,12c-CLA group than in the 9c,11t-CLA group. CONCLUSIONS: These results demonstrated that the hypolipidemic effect and the enhancement of energy metabolism by CLA can be attributed to the effect of the 10t,12c-CLA isomer.     

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.     

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.     

Conjugated linoleic acid supplementation alters the 6-mo change in fat oxidation during sleep

BACKGROUND: Conjugated linoleic acid (CLA) is a family of positional and geometric isomers with 2 conjugated double bonds formed from linoleic acid and linolenic acid. CLA has a wide range of biological effects, including body fat reduction. OBJECTIVE: The aim of our study was to determine CLA's effects on energy expenditure, macronutrient utilization, and dietary fat oxidation in overweight adults after 6 mo of supplementation. DESIGN: We recruited 23 subjects from our main CLA efficacy study who were receiving either 4 g/d of 78% active CLA isomers (3.2 g/d: 39.2% cis-9,trans-11 and 38.5% trans-10,cis-12) or 4 g/d of safflower oil. Energy expenditure and substrate utilization were measured before and after 6 mo of CLA supplementation by using whole-room indirect calorimetry. Dietary fat oxidation was measured by using stable isotope-labeled oleate and palmitate. RESULTS: Our substudy detected a difference in the change in fat utilization between the CLA (4 +/- 8 g) and placebo (-7 +/- 11 g) groups during sleep after 6 mo of supplementation. In addition, the percentage of energy from protein was reduced during sleep in the CLA group (CLA: -3.3 +/- 2.6%; placebo: 0.3 +/- 5.7%). We also detected a difference in the change in energy expenditure during sleep (CLA: 0 +/- 38 kcal; placebo: -43 +/- 90 kcal). We did not detect a change in labeled dietary fat oxidation after 6 mo of CLA supplementation given with a breakfast meal. CONCLUSION: Mixed isomer CLA supplementation, but not placebo, positively altered fat oxidation and energy expenditure during sleep.     

Isomer-specific effect of conjugated linoleic acid on inflammatory adipokines associated with fat accumulation in 3T3-L1 adipocytes

The purpose of this study was to examine the isomer-specific effect of conjugated linoleic acid (CLA) on inflammatory markers associated with fat accumulation in cultures of differentiating 3T3-L1 adipocytes. trans-10,cis-12 CLA (t10c12 CLA) reduced leptin secretion and fat accumulation. Linoleic acid (LA) and cis-9,trans-11 CLA (c9t11 CLA) increased them, but not significantly. t10c12 CLA and LA showed similar effects on mRNA expression of inflammatory markers. t10c12 CLA and LA tended to up-regulate the mRNA levels of inflammatory cytokines such as interleukin (IL)-6 (not significantly), tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP) with no significant change in the secretion of adiponectin, an anti-inflammatory adipokine. However, c9t11 CLA induced no significant change in the mRNA expression of IL-6, TNF-alpha, or CRP, but significantly increased adiponectin secretion. In conclusion, CLA exerted isomer-specific effects on fat accumulation and mRNA expression of inflammatory markers in 3T3-L1 adipocytes. t10c12 CLA up-regulated inflammatory markers in spite of the decreased fat accumulation, and TNF-alpha might be one of the causal factors.     

The combination of dietary conjugated linoleic acid and treadmill exercise lowers gain in body fat mass and enhances lean body mass in high fat-fed male Balb/C mice

Nearly half of the U.S. adult population is overweight or obese, which may be related to increased energy intake combined with lack of physical activity. Obesity increases the risk of several chronic diseases including diabetes, coronary heart disease, hypertension, and stroke. Conjugated linoleic acids (CLA) were shown to decrease fat and increase lean mass in several animal studies. However, the effects of CLA in combination with exercise (Ex) on body composition have not been studied in an animal model. We examined the effect of a low concentration of either safflower oil as control (0.5%) or mixed isomers of CLA (0.4%) along with treadmill exercise on body composition in male Balb/C mice fed a high-fat diet (20% corn oil) in a 2 x 2 factorial design. CLA consumption lowered change in fat mass (P < 0.001) confirming the results of other studies, and change in fat mass decreased further (P < 0.001) with CLA and exercise. Change in lean mass did not increase with exercise alone; it increased, although not significantly, with CLA alone and increased significantly (P < 0.05) due to the combination of CLA and exercise. This effect was accompanied by decreased serum leptin levels and lower leptin mRNA expression in peritoneal fat (P < 0.001). Serum insulin, glucose, tumor necrosis factor (TNF)-alpha, and interleukin-6 were lower in CLA-fed mice than in controls (P < 0.05), whereas serum TNF-alpha was increased by exercise (P < 0.05). Exercise increased oxygen consumption and energy expenditure when measured under resting conditions (P < 0.05). In summary, the combination of dietary CLA and exercise decreased fat mass and increased lean mass in mice fed a high-fat diet, and these effects may be related in part to decreased serum leptin and exercise-induced increases in oxygen consumption and energy expenditure.     

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.     

Dietary trans-10, cis-12 and cis-9,trans-11 conjugated linoleic acids induce apoptosis in the colonic mucosa of rats treated with 1,2-dimethylhydrazine

We have previously shown that a diet containing a mixture of conjugated linoleic acid (CLA) isomers reduces the incidence of colon tumors in rats treated with 1,2-dimethylhydrazine (DMH). The present study examined which of the two main CLA isomers, trans-10,cis-12 CLA (t10c12) or cis-9,trans-11 CLA (c9t11), decreases colon tumor numbers and the mechanisms for this effect. Six-week-old, male Sprague-Dawley rats were intramuscularly injected with 15 mg/kg of DMH twice per week for 6 weeks and fed a control diet, 1% t10c12, or 1% c9t11 for 30 weeks. The experimental diets were initiated simultaneously with DMH injection. The tumor numbers were decreased and the apoptotic index was significantly increased in the colonic mucosa of the t10c12 and c9t11 groups, when the results were compared with those of the control group. The protein levels of Bcl-2 and cyclooxygenase-2 were significantly decreased, but Bax levels were increased in both of the CLA isomer groups. The thromboxane B(2) levels in colonic mucosa were substantially lower in the two CLA isomer groups than in the control group. However, there was no difference in these parameters between the CLA isomer groups. We have demonstrated that diets containing 1% t10c12 and c9t11 were equally effective in reducing tumor numbers and inducing apoptosis in the colonic mucosa of rats treated with DMH. These results indicate that Bcl-2 family protein levels are associated with CLA-induced apoptosis in the colonic mucosa of DMH-treated rats.