Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognized class of anticarcinogens

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.

Effect of conjugated linoleic acid on body composition in mice

8-hydroxy-2′-deoxyguanosine (8-OH-dG) was first reported in 1984 as a major form of oxidative DNA damage product by heated sugar, Fenton-type reagents and X-irradiation in vitro. 8-OH-dG has been detected in cellular DNA using an HPLC-ECD method in many laboratories. Analyses of 8-OH-dG in animal organ DNA after the administration of oxygen radical-forming chemicals will be useful for assessments of their carcinogenic risk. Its analysis in human leucocyte DNA and in urine is a new approach to the assessment of an individual's cancer risk due to oxidative stress. The increase of the 8-OH-dG level in the cellular DNA, detected by HPLC-ECD method, was supported by its immunochemical detection and its enhanced repair activity. The validity of the general use of 8-OH-dG as a marker of cellular oxidative stress is discussed.

Analysis of a form of oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis

The Biologically Active Isomers of Conjugated Linoleic Acid

Conjugated linoleic acid (CLA) is a naturally occurring anticarcinogen found in milk fat and body fat of ruminants. Although CLA is an intermediate in ruminal biohydrogenation of linoleic acid, we hypothesized that its primary source was from endogenous synthesis. This would involve Delta(9)-desaturase and synthesis from trans-11 18:1, another intermediate in ruminal biohydrogenation. Our first experiment supplied lactating cows (n = 3) with trans-11 18:1 by abomasal infusion and examined the potential for endogenous synthesis by measuring changes in milk fat CLA. By d 3, infusion of trans-11 18:1 resulted in a 31% increase in concentration of cis-9, trans-11 CLA in milk fat, demonstrating that an active pathway for endogenous synthesis of CLA exists. Our second experiment examined the quantitative importance of endogenous synthesis of CLA in lactating cows (n = 3) by abomasally infusing a putative stimulator (retinol palmitate) or an inhibitor (sterculic oil) of Delta(9)-desaturase. Infusion of retinol palmitate had no influence on milk fatty acid desaturation, and yield of CLA in milk fat was not altered. However, sterculic oil infusion decreased the concentration of CLA in milk fat by 45%. Consistent with Delta(9)-desaturase inhibition, the sterculic oil treatment also altered the milk fat concentration of other Delta(9)-desaturase products as indicated by the two- to threefold increase in the ratios of 14:0 to 14:1(,) 16:0 to 16:1 and 18:0 to cis-18:1. Using changes in the ratio of 14:0 to 14:1 as an indication of the extent of Delta(9)-desaturase inhibition with the sterculic oil treatment, an estimated 64% of the CLA in milk fat was of endogenous origin. Overall, results demonstrate that endogenous synthesis of CLA from trans-11 18:1 represented the primary source of CLA in milk fat of lactating cows.

Conjugated linoleic acid is synthesized endogenously in lactating dairy cows by Delta(9)-desaturase.

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.

Evidence that the trans -10, cis -12 isomer of conjugated linoleic acid induces body composition changes in mice

Grilled ground beef contains factors that inhibit the initiation of mouse epidermal carcinogenesis by 7,12-dimethylbenz(a)anthracene. Previously we isolated an active principal and characterized it as an isomeric mixture of conjugated dienoic derivatives of linoleic acid (CLA). We now show that synthetic CLA inhibits the initiation of mouse forestomach tumorigenesis by benzo(a)pyrene. Four and 2 days prior to p.o. treatment with benzo(a)pyrene, female ICR mice were given (a) CLA in olive oil, (b) linoleic acid in olive oil, or (c) olive oil alone or plus 0.85% saline (control groups). Three days later the cycle was repeated for a total of 4 times. At 30 wk of age, the mice were sacrificed. In three independent experiments, mice treated with CLA developed only about half as many neoplasms/animal as mice in the control groups (P

https://cancerres.aacrjournals.org/content/canres/50/4/1097.full.pdf

Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid.

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.

Jayne M. Storkson

Papers

Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognized class of anticarcinogens

Effect of conjugated linoleic acid on body composition in mice

Evidence that the trans -10, cis -12 isomer of conjugated linoleic acid induces body composition changes in mice

Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid.

Changes in body composition in mice during feeding and withdrawal of conjugated linoleic acid