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LE Magazine August 2002

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Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits.

OBJECTIVE: To determine effects of conjugated linoleic acid (CLA) on the establishment and progression of experimentally-induced atherosclerosis in rabbits. METHODS: For establishment of atherosclerosis, New Zealand White rabbits were fed a semipurified diet containing 0.1% to 0.2% cholesterol for 90 days. Some groups were fed diet and CLA. For effects on progression of atherosclerosis, rabbits with established atherosclerosis were fed a semipurified diet +/- CLA for 90 days. RESULTS: At dietary levels as low as 0.1%, CLA inhibited atherogenesis. At dietary levels of 1%, CLA caused substantial (30%) regression of established atherosclerosis. This is the first example of substantial regression of atherosclerosis being caused by diet alone. CONCLUSION: Dietary CLA is an effective inhibitor of atherogenesis and also causes regression of established atherosclerosis.

J Am Coll Nutr 2000 Aug;19(4):472S-477S

Effect of conjugated linoleic acid on body composition in mice.

The effects of conjugated linoleic acid (CLA) on body composition were investigated. ICR mice were fed a control diet containing 5.5% corn oil or a CLA-supplemented diet (5.0% corn oil plus 0.5% CLA). Mice fed CLA-supplemented diet exhibited 57% and 60% lower body fat and 5% and 14% increased lean body mass relative to controls (P < 0.05). Total carnitine palmitoyltransferase activity was increased by dietary CLA supplementation in both fat pad and skeletal muscle; the differences were significant for fat pad of fed mice and skeletal muscle of fasted mice. In cultured 3T3-L1 adipocytes CLA treatment (1 x 10(-4)M) significantly reduced heparin-releasable lipoprotein lipase activity (-66%) and the intracellular concentrations of triacylglyceride (-8%) and glycerol (-15%), but significantly increased free glycerol in the culture medium (+22%) compared to control (P < 0.05). The effects of CLA on body composition appear to be due in part to reduced fat deposition and increased lipolysis in adipocytes, possibly coupled with enhanced fatty acid oxidation in both muscle cells and adipocytes.

Lipids 1997 Aug;32(8):853-8

Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomized controlled trial.

BACKGROUND: Abdominal obesity is strongly related to metabolic disorders. Recent research suggests that dietary conjugated linoleic acid (CLA) reduces body fat and may improve metabolic variables in animals. The metabolic effects of CLA in abdominally obese humans have not yet been tested. OBJECTIVE: To investigate the short-term effect of CLA on abdominal fat and cardiovascular risk factors in middle-aged men with metabolic disorders. METHODS: Twenty-five abdominally obese men (waist-to-hip ratio (WHR), 1.05+/-0.05; body mass index (BMI), 32+/-2.7 kg/m(2) (mean+/-s.d.)) who were between 39 and 64-y-old participated in a double-blind randomised controlled trial for 4 weeks. Fourteen men received 4.2 g CLA/day and 10 men received a placebo. The main endpoints were differences between the two groups in sagittal abdominal diameter (SAD), serum cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, free fatty acids, glucose and insulin. RESULTS: At baseline, there were no significant differences between groups in anthropometric or metabolic variables. After four weeks there was a significant decrease in SAD (cm) in the CLA group compared to placebo (P=0.04, 95% CI; -1.12, -0.02). Other measurements of anthropometry or metabolism showed no significant differences between the groups. CONCLUSIONS: These results indicate that CLA supplementation for four weeks in obese men with the metabolic syndrome may decrease abdominal fat, without concomitant effects on overall obesity or other cardiovascular risk factors. Because of the limited sample size, the effects of CLA in abdominal obesity need to be further investigated in larger trials with longer duration.

Int J Obes Relat Metab Disord 2001 Aug;25(8):1129-35

Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse.

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in the fat of beef and other ruminants. CLA is reported to have effects on both tumor development and body fat in animal models. To further characterize the metabolic effects of CLA, male AKR/J mice were fed a high-fat (45 kcal%) or low-fat (15 kcal%) diet with or without CLA (2.46 mg/kcal; 1.2% and 1.0% by weight in high- and low-fat diets, respectively) for six weeks. CLA significantly reduced energy intake, growth rate, adipose depot weight, and carcass lipid and protein content independent of diet composition. Overall, the reduction of adipose depot weight ranged from 43% to 88%, with the retroperitoneal depot most sensitive to CLA. CLA significantly increased metabolic rate and decreased the nighttime respiratory quotient. These findings demonstrate that CLA reduces body fat by several mechanisms, including a reduced energy intake, increased metabolic rate, and a shift in the nocturnal fuel mix.

Am J Physiol 1998 Sep;275(3 Pt 2):R667-72

Dietary conjugated linoleic acids increase lean tissue and decrease fat deposition in growing pigs.

Conjugated linoleic acid (CLA) decreases the body fat content of rodents. The aim of this study was to determine whether dietary CLA altered carcass composition of pigs. Female Large White x Landrace pigs (n = 66) were used in this study. To obtain initial body composition, six pigs were slaughtered at 57 kg live weight, whereas the remaining pigs were allocated to one of six dietary treatments (0, 1.25, 2.5, 5.0, 7.5 and 10.0 g/kg CLA, containing 55% of CLA isomers). The diets, containing 14.3 MJ digestible energy (DE) and 9. 3 g available lysine per kg, were fed ad libitum for eight weeks. Dietary CLA had no significant effect on average daily gain (861 vs. 911 g/d for pigs fed diets with and without CLA, P = 0.15) or feed intake (2. 83 vs. 2.80 kg/d, P = 0.74). The gain to feed ratio was increased by dietary CLA by 6.3% (0.328 vs. 0.348, P = 0.009). Fat deposition decreased linearly (-8.2 +/- 2.09 g/d for each gram per kilogram increase in CLA concentration; P < 0.001) with increasing inclusion of CLA. At the highest level of CLA inclusion, fat deposition was decreased by 88 g/d (-31%). Similarly, the ratio of fat to lean tissue deposition decreased linearly (-0.093 +/- 0.0216 for each gram per kilogram increase in CLA concentration; P < 0.001) with increasing dietary CLA. The carcass lean tissue deposition response to dietary CLA was quadratic in nature and was maximized (+25%) at 5. 0 g/kg dietary CLA. Overall, dietary CLA increased the gain to feed ratio and lean tissue deposition and decreased fat deposition in finisher pigs.

J Nutr 1999 Nov;129(11):2037-42

Conjugated linoleic acid reduces body fat mass in overweight and obese humans.

Conjugated linoleic acid (CLA) has been shown to reduce body fat mass (BFM) in animals. To investigate the dose-response relationships of conjugated linoleic acid with regard to BFM in humans, a randomized, double-blind study including 60 overweight or obese volunteers (body mass index 25 to 35 kg/m(2)) was performed. The subjects were divided into five groups receiving placebo (9 g olive oil), 1.7, 3.4, 5.1 or 6.8 g conjugated linoleic acid per day for 12 weeks, respectively. Dual-energy X-ray absorptiometry was used to measure body composition [measurements at week 0 (baseline), six and 12]. Of the 60 subjects, 47 completed the study. Eight subjects withdrew from the study due to adverse events; however, no differences among treatment groups were found regarding adverse events. Repeated-measures analysis showed that a significantly higher reduction in BFM was found in the conjugated linoleic acid groups compared with the placebo group (P: = 0.03). The reduction of body fat within the groups was significant for the 3.4 and 6.8 g CLA groups (P: = 0.05 and P: = 0.02, respectively). No significant differences among the groups were observed in lean body mass, body mass index, blood safety variables or blood lipids. The data suggest that conjugated linoleic acid may reduce BFM in humans and that no additional effect on BFM is achieved with doses > 3.4 g CLA/d.

J Nutr 2000 Dec;130(12):2943-8

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% to 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 six-fold increases) compared with those consuming free fatty acid CLA (three-fold 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.

J Nutr 1999 Dec;129(12):2135-42

Carnitine/DHEA

Dehydroepiandrosterone alters Zucker rat soleus and cardiac muscle lipid profiles.

High levels of serum free fatty acids (FFA) and lower proportions of polyunsaturated (PU) FAs, specifically arachidonic acid (AA), are common in obesity, insulin resistance (IR), and type 2 diabetes mellitus. Dehydroepiandrosterone (DHEA) decreases body fat content, dietary fat consumption and insulin levels in obese Zucker rats (ZR), a genetic model of human youth onset obesity and type 2 diabetes. This study was conducted to investigate DHEA’s effects on lean and obese ZR serum FFA levels and total lipid (TL) FA profiles in heart and soleus muscle. We postulated that DHEA alters serum FFA levels and tissue TL FA profiles of obese ZR so that they resemble the levels and profiles of lean ZR. If so, DHEA may directly or indirectly alter tissue lipids, FFA flux, and perhaps lower IR in obese ZR. Lean and obese male ZR were divided into six groups with 10 animals in each: obese ad libitum control, obese pair-fed, obese DHEA, lean ad libitum control, lean pair-fed, and lean DHEA. All animals had ad libitum access to a diet whose calories were 50% fat, 30% carbohydrate and 20% protein. Only the diets of the DHEA treatment groups were supplemented with 0.6% DHEA. Pair-fed groups were given the average number of calories per day consumed by their corresponding DHEA group, and ad libitum groups had 24-h access to the DHEA-free diet. Serum FFA levels and heart and soleus TL FA profiles were measured. Serum FFA levels were higher in obese (approximately 1 mmol/L) compared to lean (approximately 0.6 mmol/L) ZR, regardless of group. In hearts, monounsaturated (MU) FA were greater and PU FA were proportionally lower in obese compared to the lean rats. In soleus, saturated and MU FA were greater and PU FA were proportionally lower in the obese compared to the lean rats. DHEA groups displayed significantly increased proportions of TL AA and decreased oleic acid in both muscle types. Mechanisms by which DHEA alters TL FA profiles are a reflection of changes occurring within specific lipid fractions such as FFA, phospholipid, and triglyceride. This study provides initial insights into DHEA’s lipid altering effects.

Exp Biol Med (Maywood) 2001 Sep;226(8):782-9

Dehydroepiandrosterone alters phospholipid profiles in Zucker rat muscle tissue.

Insulin-resistant muscle tissue contains low proportions of arachidonic acid (AA), and increased proportions of muscle AA correlate with improved insulin sensitivity. Dehydroepiandrosterone (DHEA) and AA, like the thiazolidinedione drugs that decrease insulin resistance (IR), are peroxisome proliferators. Long-chain fatty acids (FA) have been named the “one true” endogenous ligand for activating the peroxisome proliferator-activator receptor (PPAR), and DHEA has been named a “good candidate” as a naturally occurring indirect activator of PPAR. This study was conducted to determine DHEA’s effects on lipid profiles of skeletal and cardiac muscle in lean and obese Zucker rats (ZR), a model of IR, type 2 diabetes mellitus, and obesity. We hypothesize that DHEA may alter long-chain FA profiles in muscle tissue of obese rats such that they more closely resemble that of the lean. In our experiments, we employed a DHEA and a pair-fed (PF) group (n = 6) for 12 lean and 12 obese ZR. For 30 d, the diet of the two DHEA groups was supplemented with 0.6% DHEA; PF groups were given the average daily calories consumed by their corresponding treatment group. Hearts and gastrocnemius muscles were assayed for phospholipid (PL), free FA, and triglyceride (TG) FA profiles. The proportion of PL AA was significantly greater in both muscle types of lean compared to obese rats. Hearts from both DHEA groups had greater PL proportions of AA and less oleic (18:1) acid than their PF controls. Likewise, 18:1 proportions were significantly lower in the gastrocnemius; however, AA proportions were not significantly different. Similar phenotypic profile differences were observed in the TG fraction of both muscle types. There were no DHEA-related TG FA profile alterations.

Lipids 2001 Dec;36(12):1383-6


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