ABSTRACT
Conjugated linoleic acid (CLA) has been shown to reduce body fat and increase lean body mass in mice, rats, and pigs. A recent human trial indicated that CLA may work more effectively if used for prevention of body fat deposition and weight gain. To test this hypothesis, we conducted 2 experiments using relatively old mice (older than 6 mo): experiment 1, supplementation of CLA during dietary restriction and experiment 2, supplementation during ad libitum feeding followed by restriction. In experiment 1, there were significant effects of diet restriction and CLA supplementation on body composition, while CLA decreased body fat content in ad libitum diet but not significantly during diet restriction. In experiment 2, CLA fed animals had body weights similar to restricted animals and CLA significantly reduced body fat (significantly lower than prior to and post restriction, or pair fed). This suggests that CLA exerted modulation of body fat independent of reduced food intake. Based on these results, we concluded that CLA may be more effective at protecting against fat mass regain following weight loss than as a weight loss treatment.
Subject(s)
Adipose Tissue/drug effects , Anti-Obesity Agents/pharmacology , Body Composition/drug effects , Body Weight/drug effects , Linoleic Acids, Conjugated/pharmacology , Adipose Tissue/metabolism , Analysis of Variance , Animals , Dietary Fats, Unsaturated/pharmacology , Disease Models, Animal , Eating/drug effects , Female , Male , Mice , Mice, Inbred ICR , Obesity/diet therapy , Random AllocationABSTRACT
Conjugated linoleic acid (CLA) has been reported to decrease stearoyl-CoA desaturase (SCD) activity by decreasing mRNA expression. This investigation was designed to determine whether structurally related compounds of CLA have a direct inhibitory effect on SCD activity. Trans-10,cis-12 CLA had strong inhibitory activity on SCD while cis-9,trans-11, and trans-9,trans-11 isomers had no effect. Trans-10 octadecenoate was not inhibitory, whereas cis-12 octadecenate was inhibitory, but not as effective as trans-10,cis-12 CLA. Of the oxygenated derivatives, 9-peroxy-cis/trans-10, trans-12 octadecadienoate was a more effective inhibitor than trans-10,cis-12 CLA, whereas 9-hydroxy-trans-10, cis-12 octadecadienoate was less effective. Interestingly, cis-11 octadecadienoate and cis-12 octadecen-10-ynoate were slightly inhibitory. However, trans-9 and trans-11 octadecenoates, and trans-9,cis-12 octadecadienoate were all inactive under test condition, as were linoleate, oleate, and arachidonate. Derivatives of CLA acid modified to alcohol, amide or chloride were all inactive. A cis-12 double bond appears to be a key structural feature for inhibiting SCD activity, especially when coupled with a trans-10 double, whereas a cis-11 double bond is less effective.
Subject(s)
Linoleic Acids/pharmacology , Microsomes, Liver/enzymology , Stearoyl-CoA Desaturase/antagonists & inhibitors , Animals , Arachidonic Acid/pharmacology , Dose-Response Relationship, Drug , Isomerism , Linoleic Acids/chemistry , MiceABSTRACT
We investigated the effects of conjugated linoleic acid (CLA) preparations, which were enriched for the cis-9,trans-11 CLA isomer or the trans-10,cis-12 CLA isomer, on body composition in mice. Body composition changes (reduced body fat, enhanced body water, enhanced body protein, and enhanced body ash) were associated with feeding the trans-10,cis-12 CLA isomer. In cultured 3T3-L1 adipocytes, the trans-10,cis-12 isomer reduced lipoprotein lipase activity, intracellular triacylglycerol and glycerol, and enhanced glycerol release into the medium. By contrast, the cis-9,trans-11 and trans-9,trans-11 CLA isomers did not affect these biochemical activities. We conclude that CLA-associated body composition change results from feeding the trans-10,cis-12 isomer.
Subject(s)
Body Composition/drug effects , Linoleic Acids/pharmacology , 3T3 Cells/drug effects , 3T3 Cells/metabolism , Adipocytes/drug effects , Adipocytes/metabolism , Animals , Body Weight/drug effects , Dose-Response Relationship, Drug , Female , Isomerism , Linoleic Acids/chemistry , Lipoprotein Lipase/drug effects , Lipoprotein Lipase/metabolism , Male , Mice , Mice, Inbred ICR , Triglycerides/metabolismABSTRACT
Two experiments were conducted. In Experiment 1, 8-wk-old mice were fed control diet or diet supplemented with 0.5% conjugated linoleic acid (CLA) to study the effect of CLA on body composition (CLA: 40.8-41.1% c-9,t-11 isomer, 43.5-44.9% t-10,c-12 isomer). The data for CLA-fed mice vs. controls described parallel but significantly distinct responses for both absolute and relative changes in body fat mass (reduced in CLA-fed mice) and for relative changes in whole body protein and whole body water (both of which were increased in CLA-fed mice). In the CLA-fed mice, the effect on whole body protein appeared to precede the reduction in body fat mass. In Experiment 2, weanling mice were fed control diet or diet supplemented with 0.5% CLA for 4 wk (test group), at which time all mice were fed control diet devoid of added CLA. The test group exhibited significantly reduced body fat and significantly enhanced whole body water relative to controls at the time of diet change. Time trends for changes in relative body composition were described by parallel lines where the test group exhibited significantly less body fat but significantly more whole body protein, whole body water, and whole body ash than controls. Tissue CLA levels declined following the withdrawal of CLA from the diet. In skeletal muscle of mice fed CLA-supplemented diet, the t-10,c-12 isomer was cleared significantly faster than the c-9,t-11 CLA isomer.
Subject(s)
Body Composition/drug effects , Linoleic Acids/pharmacology , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Animals , Body Weight/drug effects , Diet , Eating , Female , Isomerism , Linoleic Acids/metabolism , Liver/drug effects , Liver/metabolism , Mice , Mice, Inbred ICR , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Proteins/drug effects , Proteins/metabolismABSTRACT
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.
Subject(s)
Body Composition/drug effects , Dietary Fats/pharmacology , Linoleic Acids/pharmacology , 3T3 Cells , Adipocytes/enzymology , Adipose Tissue/enzymology , Animals , Body Weight/drug effects , Carnitine O-Palmitoyltransferase/metabolism , Corn Oil/administration & dosage , Diet , Dietary Fats/administration & dosage , Female , Glycerol/metabolism , Linoleic Acids/administration & dosage , Lipolysis/drug effects , Lipoprotein Lipase/antagonists & inhibitors , Liver/enzymology , Male , Mice , Mice, Inbred ICR , Muscles/enzymologyABSTRACT
We studied the effect of conjugated linoleic acid (CLA) on rat development and growth. Primigravid female Fischer rats were fed control or CLA-supplemented (0.25% or 0.5% CLA) diets during gestation and/or lactation. Conjugated linoleic acid was incorporated into milk fat and tissue lipids proportional to the level of CLA fed and the duration of CLA feeding. Conjugated linoleic acid was incorporated into fetal and neonatal tissues; it did not affect litter size nor induce apparent abnormalities. To the contrary, feeding CLA to the dams during gestation and lactation improved the postnatal body weight gain of pups (P < 0.05), measured on d 10 of lactation. Pups that continued to receive the CLA-supplemented diet after weaning had significantly greater body weight gain and improved feed efficiency relative to control animals (P < 0.05).
Subject(s)
Diet , Growth/drug effects , Linoleic Acids, Conjugated/pharmacology , Animals , Body Weight/drug effects , Eating/drug effects , Female , Linoleic Acids, Conjugated/administration & dosage , Male , Milk/chemistry , Pregnancy , Rats , WeaningABSTRACT
Conjugated linoleic acid (CLA) is an anticarcinogen in several model animal systems. Conjugated linoleic acid occurs naturally in food and is present at higher concentrations in products from ruminant animals. Given that certain rumen microorganisms produce CLA from free linoleic acid, we studied the effect of feeding free or esterified linoleic acid on tissue CLA concentrations using conventional and germ-free rats. Conventional rats were fed a 5% (wt/wt) corn oil control diet alone or supplemented with 5% free linoleic acid or 8.63% corn oil (equivalent to 5% linoleic acid in triglyceride). Germ-free rats were fed autoclavable nonpurified diet alone or supplemented with 5% free linoleic acid. Analyses of CLA concentrations were performed on lipids extracted from liver, lung, kidney, skeletal muscle and abdominal adipose tissue, and on liver phospholipid and neutral lipid fractions. Tissue CLA concentrations were higher in conventional rats fed free linoleic acid (the major isomers were cis-9, trans-11 and trans-9, cis-11) than in control animals. Conjugated linoleic acid concentrations in free linoleic acid-fed rats were maximal at 4 wk, and levels were 5-10 times higher than those of controls. Elevated CLA concentrations were also observed in liver phospholipid and neutral lipid fractions. In contrast, CLA concentrations in the tissues of germ-free rats were not affected by diet. Feeding the corn oil-fortified diet to conventional rats did not increase CLA concentration in the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Diet , Fatty Acids, Unsaturated/biosynthesis , Germ-Free Life/physiology , Linoleic Acids, Conjugated , Linoleic Acids/biosynthesis , Linoleic Acids/metabolism , Adipose Tissue/metabolism , Administration, Oral , Animals , Chromatography, Gas , Female , Kidney/metabolism , Linoleic Acids/administration & dosage , Linoleic Acids/pharmacokinetics , Liver/metabolism , Lung/metabolism , Muscles/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Stereoisomerism , Tissue DistributionABSTRACT
It is now well documented that bacterial mutagens form in proteinaceous foods during cooking at moderate temperatures. Three heterocyclic amine mutagens have been identified by Sugimura and coworkers in fish and beef cooked under moderate heating conditions (T. Sugimura and S. Sato, Cancer Res. (Suppl.), 43: 2415s-2421s, 1983). The distribution of these known mutagens in commercial bacteriological-medium grade and food-grade beef extract, and in fried ground beef, is discussed. Of the known mutagens, we have been able to confirm only that 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline is present in fried ground beef. Deficiencies in currently used mutagen extraction procedures are addressed. It is likely that there are many mutagens in fried ground beef that are yet to be identified. Fried ground beef (and raw beef) also contains an activity which modulates bacterial mutagenesis apparently by interacting with rat liver microsomes which are added to metabolically activate promutagens. The modulator activity has been partially purified and either inhibits, enhances, or has no effect on promutagen activation depending on the promutagen under study and the pretreatment of the rat from which the microsomal fraction was obtained.
