Journal of Nutrition OpenSOurce Diets- www.ResearchDiets.com

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lock, A. L.
Right arrow Articles by Ip, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lock, A. L.
Right arrow Articles by Ip, C.
© 2004 The American Society for Nutritional Sciences J. Nutr. 134:2698-2704, October 2004

Nutrition and Cancer

The Anticarcinogenic Effect of trans-11 18:1 Is Dependent on Its Conversion to cis-9, trans-11 CLA by {Delta}9-Desaturase in Rats1

Adam L. Lock*, Benjamin A. Corl*,2, David M. Barbano{dagger}, Dale E. Bauman*,3 and Clement Ip**

* Department of Animal Science and {dagger} Department of Food Science, Cornell University, Ithaca, NY 14853; ** Department of Cancer Chemoprevention, Roswell Park Cancer Institute, Buffalo, NY 14263

3To whom correspondence should be addressed. E-mail: deb6{at}cornell.edu.


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
The present study was designed to determine whether the ability of vaccenic acid (trans-11 18:1; VA) to reduce the risk of chemically induced mammary carcinogenesis in rats is direct or is mediated via conversion to cis-9, trans-11 conjugated linoleic acid (CLA). We previously reported that dietary VA caused a dose-dependent increase in the accumulation of CLA in the mammary fat pad, which was accompanied by a parallel decrease in the risk of mammary tumorigenesis. Specifically, our objective was to determine whether inhibiting {Delta}9-desaturase with cyclopropenoic fatty acids, supplied by sterculic oil (SO), would reverse the cancer-protective effect observed with a dietary supplement of VA-enriched butter. Female Sprague-Dawley rats were injected with a single dose of carcinogen (methylnitrosourea) and were fed 1 of 4 diets: 1) low VA (0.13% of diet), 2) low VA + SO (0.4% of diet), 3) high VA (1.60% of diet), and 4) high VA + SO. After 6 wk, the mammary glands were evaluated histologically for the appearance of premalignant lesions and were stained with bromodeoxyuridine to determine the extent of cell proliferation, and fatty acids were analyzed in plasma, liver, and mammary fat pad. The VA-enriched diet increased the tissue content of CLA, reduced the risk of developing premalignant lesions, and decreased the proliferative activity of premalignant cells in the mammary gland. Treatment with SO reversed the effects of VA. The anticarcinogenic effect of VA is predominantly, perhaps exclusively, mediated through its conversion to cis-9, trans-11 CLA via {Delta}9-desaturase, and when this conversion is blocked by SO, the biological response to VA is attenuated.

KEY WORDS: • conjugated linoleic acid • vaccenic acid • {Delta}9-desaturase • mammary cancer prevention • functional food

Conjugated linoleic acid (CLA)4 isomers have been shown to possess a number of health benefits in biomedical studies with animal models (1–3). Dairy products are the principal source of CLA in human diets (4), with the cis-9, trans-11 isomer representing 75–90% of total CLA in dairy foods (5,6). Endogenous synthesis from vaccenic acid (trans-11 18:1; VA), the major biohydrogenation intermediate produced in the rumen, is the predominant source of cis-9, trans-11 CLA in milk fat. Due to the precursor–product relation between these 2 fatty acids, foods rich in CLA are generally also rich in VA. In addition to ruminants, the conversion of VA to cis-9, trans-11 CLA has been reported in rodents and humans [see review by Bauman et al. (6)].

The ability of CLA to prevent cancer has been extensively investigated by using animal models and in vitro cell cultures [see reviews by Belury (1) and Ip et al. (7)]. Cis-9, trans-11 CLA has anticarcinogenic activity in animal tumor models, and we first demonstrated that feeding a CLA-enriched butter fat was effective in reducing the risk of mammary cancer in rats that were treated with a chemical carcinogen (8). Banni et al. (9) found that a dose-dependent increase in the tissue concentration of cis-9, trans-11 CLA occurred in response to the feeding of pure VA, and this was accompanied by a progressive reduction in the number of premalignant lesions in the mammary gland. In a longer-term study, similar increases in tissue CLA content were obtained in the same rat model when varying amounts of VA were supplied by feeding a naturally enriched butter, and the increase corresponded to a reduction in mammary tumors (10). These findings established that VA was anticarcinogenic; however, it was not clear whether this effect was due to VA per se or if conversion to cis-9, trans-11 CLA was required.

The endogenous synthesis of cis-9, trans-11 CLA from VA is dependent on {Delta}9-desaturase, and sterculic acid is a specific inhibitor of this enzyme (11,12). The objective of the present study was to determine whether treatment with sterculic oil (SO), which serves as a source of sterculic acid, would reverse the cancer-preventative effect of dietary VA by inhibiting its conversion to cis-9, trans-11 CLA. Due to concerns of possible secondary effects with long-term use of SO and limitations in its supply, we used histologically confirmed mammary premalignant lesions as the end point of analysis. The development of these premalignant lesions is detectable within a few weeks after carcinogen treatment and is closely correlated with the risk of mammary carcinoma formation (13).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 LITERATURE CITED
 
    Treatment protocol of animal carcinogenesis experiment. Female Sprague-Dawley rats were purchased from Charles River Breeding Laboratories at 45 d of age; all subsequent procedures were approved by the Roswell Park Cancer Institute Animal Care and Use Committee. Rats were fed the AIN-76 basal diet, as described previously (10), for 1 wk to acclimate them to the powdered diet. All rats were injected with a single dose of methylnitrosourea (MNU: 50 mg/kg body wt) intraperitoneally at 50 d of age for the induction of premalignant lesions in the mammary gland. Immediately after MNU administration, the rats (n = 72) were divided into 4 equal groups and were fed either a low- or a high-VA diet, with or without SO (Table 1). The low VA diets (L-VA, L-VA+SO) included a control butter and the high VA diets (H-VA, H-VA+SO) used a VA/CLA-enriched butter that was produced by feeding cows a natural diet that was specifically formulated for this purpose (14). The fatty acid composition of the control and VA/CLA butters, as well as the composition of the control and VA/CLA-enriched diets, were described previously (10). To achieve a constant dietary content of cis-9, trans-11 CLA, a synthetic cis-9, trans-11 CLA (Natural; 90% purity) was added to the control butter diets. Rats were fed these diets for 6 wk. Nine rats from each group were injected intraperitioneally with bromodeoxyuridine (BrdU) at a dose of 50 mg/kg body wt, 6 h before killing. At necropsy, the whole mammary gland on both sides was excised and processed for histological evaluation of premalignant lesions and BrdU labeling. The remaining 9 rats from each group were not injected with BrdU, and the liver, plasma, and mammary fat pad from these animals were used for fatty acid analysis.


View this table:
[in this window]
[in a new window]
  		TABLE 1 Design of diets containing control butterfat and/or VA/CLA-enriched butterfat and SO

 
    Quantification of premalignant lesions in the mammary gland. The abdominal–inguinal mammary gland chains were fixed in methacarn and were processed in a Tissue-Tek Vacuum Infiltration Processor (Miles Scientific). Each mammary gland whole mount was divided into 6 segments, and these were embedded in paraffin blocks. Ribbons of 5-µm thickness were cut from each block and were placed on slides that had been treated with 3-aminopropyltriethoxysilane. Every 10th section was heat immobilized, deparaffinized in xylene, rehydrated in descending grades of ethanol (100–70%), and stained with hematoxylin and eosin (H&E). These H&E slides were examined under the microscope for the appearance of premalignant lesions by using the criteria described by Russo et al. (15) and, as expected, all rats had developed premalignant lesions in response to the relatively large dose of carcinogen. Once a section showing such pathology was found, the contiguous slides were similarly stained and examined. The size of each premalignant lesion could thus be estimated operationally by the number of serial sections showing the same pathology. Colored micrographs of these premalignant lesions have been published previously (16).

    Evaluation of proliferative activity by BrdU labeling. Slide preparation for this assay was similar to that described above. Mouse anti-BrdU antibody (Becton Dickinson) was applied at a dilution of 1:40 for 60 min. After the tissue sections were incubated with the primary antibody at room temperature in a humid chamber, they were treated with a biotinylated rabbit secondary antibody against mouse immunoglobulin. This was followed by the addition of streptavidin-horseradish peroxidase, which binds to biotin. Diaminobenzidine was used as the chromogen to generate a brown precipitate, because of its reaction with peroxidase. All slides were counterstained with H&E, rinsed, dehydrated, and mounted with Permount. Cells expressing the antigen were identified by a brown stain over the nucleus. Color pictures were taken with a camera mounted on top of the microscope. To avoid bias, all hard-copy images were coded so that the person analyzing the data was unaware of the group assignment.

    Fatty acid analysis. The –80°C samples of liver and mammary fat pad were pulverized at liquid nitrogen temperature. Total lipids were extracted from pulverized tissues and plasma by the procedure of Hara and Radin (17) by using a mixture of hexane and isopropanol. Fatty acids were methylated according to Christie (18), with modifications as described by Corl et al. (10). FAME were analyzed by GC (Hewlett Packard GC system 6890+ with flame ionization detector) using a CP-Sil 88 capillary column (100 m x 0.25 mm internal diameter with 0.2-µm film thickness; Varian). A programmed temperature run was used to separate FAME. The oven temperature was initially maintained at 70°C for 2 min, then increased at 8°C/min to 110°C, and held for 4 min. The temperature was then increased at 5°C/min to 170°C and held for 10 min. Finally it was increased at 4°C/min to 225°C and held for 15 min. Injector and detector temperatures were maintained at 250°C. The split ratio was 100:1, and hydrogen was used as the carrier gas at 2.1 mL/min. FAME standards were used to identify sample FAME (Nu-Chek Prep).

    Statistical analyses. The premalignant lesion data were analyzed by the {chi}2 test by using a Poisson regression model (19). Differences in BrdU staining between groups were analyzed using a Kruskal-Wallis rank test (20). Fatty acid data were analyzed by the general linear model procedure of SAS (SAS Institute). ANOVA was used to identify the effect of treatment and differences between treatment means were identified using the probability of difference option of the LSMeans command. Treatment effects and differences between means were considered significant when P < 0.05.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 LITERATURE CITED
 
    Modulation of mammary cancer risk and proliferative activity. A high intake of VA reduced the total number of premalignant lesions by almost 50% (Table 2; treatment L-VA vs. H-VA). Premalignant lesions in the mammary gland were categorized into 5 size classes; the small sample size precluded a meaningful statistical analysis within a size category, but the decrease in total number was accounted for primarily by a reduced population of the larger lesions (>200 µm). Treatment with SO had no effect on the development of lesions in the L-VA group (treatment L-VA vs. L-VA+SO), but appeared to reverse the inhibitory effect of the H-VA group (treatment H-VA vs. H-VA+SO).


View this table:
[in this window]
[in a new window]
  		TABLE 2 Effect of low or high doses of VA, with or without SO, on the modulation of mammary premalignant lesion development of rats1

 
Proliferative activity of premalignant lesions and normal alveolar epithelial cells of the mammary gland was determined by BrdU labeling (Table 3). The VA-enriched diet reduced the proportion of BrdU-positive cells in the premalignant lesions (treatment L-VA vs. H-VA), but had no effect on the normal alveolar cell population. Treatment with SO negated the inhibitory effect of the high dietary intake of VA on cell proliferation of the premalignant lesions (treatment H-VA vs. H-VA+SO).


View this table:
[in this window]
[in a new window]
  		TABLE 3 Effect of low or high doses of VA, with or without SO, on BrdU labeling of premalignant cells and normal alveolar cells of the mammary gland of rats1

 
    Fatty acid analysis of tissue and plasma lipids. With each tissue and plasma, the fatty acid composition was similar across treatments with the exception of those fatty acids that were either substrates or products of {Delta}9-desaturase (Tables 4, , 5, , and 6). As expected, increasing the VA content of the diet from 0.13 to 1.60% resulted in substantial increases in the concentration of cis-9, trans-11 CLA. Comparing treatments L-VA and H-VA, the proportion of fatty acids as cis-9, trans-11 CLA was increased by 193, 177, and 123% in liver, plasma, and mammary fat pad, respectively. Treatment with SO did not reduce the fatty acid content of cis-9, trans-11 CLA at the low intake of VA (treatment L-VA vs. L-VA+SO), but at the high intake of VA, it significantly decreased in the concentration of cis-9, trans-11 CLA in the liver, plasma, and mammary fat pad. This was greatest in the mammary fat pad where the dietary addition of SO reduced cis-9, trans-11 CLA by almost 40% (treatment H-VA vs. H-VA+SO). The reduced concentration of cis-9, trans-11 CLA in treatment H-VA+SO was associated with an accumulation of VA, consistent with the action of SO inhibiting the endogenous synthesis of cis-9, trans-11 CLA via {Delta}9-desaturase. The presence of SO at both the low and the high doses of VA altered additional fatty acid substrate:product pairs associated with {Delta}9-desaturase. This enzyme can add a cis-9 double bond to 14:0, 16:0, and 18:0 to produce cis-9 14:1, cis-9 16:1, cis-9 18:1, respectively, and, in most cases, differences in these fatty acid pairs was evident. An exception was when substrate supply was low, at which time the addition of SO to the diet had no effect on these fatty acid pairs; this was apparent at the low dose of VA when SO did not reduce tissue concentrations of cis-9, trans-11 CLA (treatment L-VA vs. L-VA+SO). However, comparing the same dietary treatments, SO significantly reduced the mammary fat pad concentrations of cis-9 14:1, cis-9 16:1, and cis-9 18:1 and, by the same token, increased the concentrations of 14:0, 16:0, and 18:0. These changes are reflected in their respective {Delta}9-desaturase indices [(product) ÷ (substrate + product)], and alterations in these were similar across the low and high doses of VA (treatments L-VA vs. L-VA+SO and H-VA vs. H-VA+SO), indicating similar efficacy in the inhibition of {Delta}9-desaturase in both treatments (L-VA+SO and H-VA+SO; Fig. 1). Total and individual isomers of trans fatty acids were increased in treatments H-VA and H-VA+SO consistent with their increased supply in the diet.


View this table:
[in this window]
[in a new window]
  		TABLE 4 Composition of fatty acids from liver lipids of rats fed low or high doses of VA, with or without SO1

 

View this table:
[in this window]
[in a new window]
  		TABLE 5 Composition of fatty acids from plasma lipids of rats fed low or high doses of VA, with or without SO1

 

View this table:
[in this window]
[in a new window]
  		TABLE 6 Composition of fatty acids from mammary fat pad lipids of rats fed low or high doses of VA, with or without SO1

 


View larger version (19K):
[in this window]
[in a new window]
  		FIGURE 1 The effect of SO on fatty acid {Delta}9-desaturase indices in the mammary fat pad. Indices are defined as the ratio of [{Delta}9-desaturase product] ÷ [{Delta}9-desaturase product plus substrate]. Panel I, cis-9 14:1/ 14:0 + cis-9 14:1); Panel II, cis-9 16:1/(16:0 + cis-9 16:1); Panel III, cis-9 18:1/(18:0 + cis-9 18:1); Panel IV, cis-9, trans-11 CLA/trans-11 18:1 + cis-9, trans-11 CLA). Data are means, and SEM was 0.004, 0.003, 0.003, and 0.001 for data in Panels I, II, III, and IV, respectively. Means without a common letter differ, P < 0.05.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
LITERATURE CITED
 
Previous studies with rats showed that dietary supplementation with pure VA or VA-enriched butter resulted in an increased tissue accumulation of cis-9, trans-11 CLA; this was accompanied by a reduced risk of mammary carcinogenesis (9,10). In the present report, we extended the above finding by demonstrating that the anticarcinogenic effect of VA was lost when {Delta}9-desaturase was inhibited by SO, suggesting that the conversion of VA to cis-9, trans-11 CLA is a vital step in the response to VA. SO contains cyclopropenoic fatty acids, which are the specific inhibitors of {Delta}9-desaturase (12). These cyclopropenoic fatty acids downregulate enzyme activity, possibly by a turnover dependent reaction without affecting gene or protein expression (11). At high doses (≥1% in the diet), some investigators have observed adverse effects on growth and other physiological processes (21–24). To arrive at a dose of SO, we conducted a preliminary study comparing different doses on the ratio of fatty acid pairs that represent substrate:product for {Delta}9-desaturase; the dose chosen (0.25% cyclopropenoic fatty acids) represented the lowest dose where a substantial shift in the desaturase ratios occurred in liver lipid. In the present experiment, we did not experience any change in weight gain between the treated and the untreated rats (data not shown), and the predominant effects on tissue and plasma fatty acid composition were related to those fatty acids that are either substrates or products of {Delta}9-desaturase. Based on the results of Tables 4, , 5, , and 6, we concluded that the inhibition of {Delta}9-desaturase by SO was not complete. Thus, we cannot totally rule out a direct action of VA. Nonetheless, the evidence is rather compelling in favor of a predominant mechanism mediated through its conversion to cis-9, trans-11 CLA.

The {Delta}9-desaturase (also referred to as stearoyl-CoA desaturase; EC 1.14.99.5) catalyzes the addition of a cis-9 double bond in the biosynthesis of a number of monounsaturated fatty acids and was shown to be present in several tissues, including the mammary gland, adipose, liver, and intestine. Dietary factors (e.g., glucose and polyunsaturated fatty acids) and hormones (e.g., insulin, glucagon, and thyroid hormone) modulate gene expression and protein level of this enzyme [see review by Ntambi and Miyazaki (25)]. Endogenous synthesis via {Delta}9-desaturase is the major source of cis-9, trans-11 CLA in ruminant milk fat [see review by Bauman et al. (6)]. In ruminants, the precursor is VA formed as an intermediate in rumen biohydrogenation of linoleic and linolenic acids, and VA is typically the major intermediate leaving the rumen (26,27). The conversion of VA to cis-9, trans-11 CLA has also been reported in a number of species, including rodents (8–10,28), pigs (29), and humans (30–32). In humans, the VA is of dietary origin, and Turpeinen et al. (32) using tracer kinetics found that ~20% of VA was converted to cis-9, trans-11 CLA.

Current public health policy strongly recommends a reduction in the intake of trans fatty acids, principally due to their putative association with elevated plasma concentrations of cholesterol and LDL, along with lower concentrations of HDL (33,34). VA is the predominant trans fatty acid present in ruminant products, accounting for 60–80% of the total (35,36), whereas industrial sources of trans fatty acids in the human diet typically contain a Gaussian distribution of trans 18:1 isomers that centers on trans-9, trans-10, trans-11, and trans-12 (35,36). In the present study, we show that the beneficial effects of VA in reducing the development of premalignant lesions and proliferative activity of these cell populations are related to its use for endogenous synthesis of cis-9, trans-11 CLA.

There is increasing consumer awareness of functional food components that may have beneficial effects on human health above that expected on the basis of nutritive value. A number of components in milk fat have anticarcinogenic properties (3,37), and this includes both VA and cis-9, trans-11 CLA. As a result of these beneficial health properties, recent research has focused on enriching milk and dairy products with cis-9, trans-11 CLA [see reviews by Bauman et al. (38) and Stanton et al. (39)]. Due to the unique precursor:product relation between VA and cis-9, trans-11 CLA in dairy cows, efforts to increase the cis-9, trans-11 CLA content of milk will lead to inevitable increases in the VA content as well. Based on the typical relation between VA and cis-9, trans-11 CLA in ruminant fat and the extent of conversion of VA to cis-9, trans-11 CLA in humans (32), Parodi (5) suggested that multiplying the cis-9, trans-11 CLA intake from human diets by 1.4 provides an estimate of the effective physiological dose of cis-9, trans-11 CLA derived from ruminant products. In attempting to produce modified products of this nature, it is important to take into account the effects on organoleptic and storage qualities of the final product. We recently showed that by feeding dairy cows natural diets similar to those used to make the butter in the current study, there were no differences in taste and storage characteristics of a 2% fat milk in which ~20% of the total fatty acids were VA and cis-9, trans-11 CLA compared with a standard 2% fat milk (40). Overall, the present study clearly shows that both VA and cis-9, trans-11 CLA present in milk fat are anticarcinogenic, with the {Delta}9-desaturase enzyme system being key in differentiating VA from other trans 18:1 fatty acids.


   ACKNOWLEDGMENTS
 
The authors thank Todd Parsons, Cassandra Hayes, Joanna Lynch, Jim Perfield, and Debbie Dwyer for their technical assistance.


   FOOTNOTES
 
1 Supported by grants to C.I. and D.E.B. from the National Dairy Council, Rosemont, IL; grant CA 61763 from the National Cancer Institute, National Institute of Health; and Roswell Park Cancer Institute Core grant CA 16056 awarded by the National Cancer Institute. Support was also received from Northeast Dairy Foods Research Center and Cornell University Agricultural Experimental Station. Back

2 Current address: Department of Animal Science, Box 7621, North Carolina State University, Raleigh, NC 27695-7621. Back

4 Abbreviations used: BrdU, bromodeoxyuridine; CLA, conjugated linoleic acid; L-VA, low vaccenic acid diet; L-VA+SO, low vaccenic acid with sterculic oil diet; H&E, hematoxylin and eosin; H-VA, high vaccenic acid diet; H-VA+SO, high vaccenic acid with sterculic oil diet; MNU, methylnitrosourea; SO, sterculic oil; VA, vaccenic acid. Back

Manuscript received 17 May 2004. Initial review completed 7 July 2004. Revision accepted 13 July 2004.


   LITERATURE CITED
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 

1. Belury, M. A. (2002) Dietary conjugated linoleic acid in health: physiological effects and mechanisms of action. Annu. Rev. Nutr. 22:505-531.[Medline]

2. Whigham, L. D., Cook, M. E. & Atkinson, R. L. (2000) Conjugated linoleic acid: implications for human health. Pharmacol. Res. 42:503-510.[Medline]

3. Parodi, P. W. (1999) Conjugated linoleic acid and other anticarcinogenic agents of bovine milk fat. J. Dairy Sci. 82:1339-1349.[Abstract]

4. Ritzenthaler, K. L., McGuire, M. K., Falen, R., Shultz, T. D., Dasgupta, N. & McGuire, M. A. (2001) Estimation of conjugated linoleic acid intake by written dietary assessment methodologies underestimates actual intake evaluated by food duplicate methodology. J. Nutr. 131:1548-1554.[Abstract/Free Full Text]

5. Parodi, P. W. (2003) Conjugated linoleic acid in food. Sébédio, J.-L. Christie, W. W. Adlof, R. O. eds. Advances in Conjugated Linoleic Acid Research 2:101-122 AOCS Press Champaign, IL. .

6. Bauman, D. E., Corl, B. A. & Peterson, D. G. (2003) The biology of conjugated linoleic acids in ruminants. Sébédio, J.-L. Christie, W. W. Adlof, R. O. eds. Advances in Conjugated Linoleic Acid Research 2:146-173 AOCS Press Champaign, IL. .

7. Ip, M. M., Masso-Welch, P. A. & Ip, C. (2003) Prevention of mammary cancer with conjugated linoleic acid: role of the stroma and epithelium. J. Mammary Gland Biol. Neoplasia 8:103-118.[Medline]

8. Ip, C., Banni, S., Angioni, E., Carta, G., McGinley, J., Thompson, H. J., Barbano, D. & Bauman, D. E. (1999) Conjugated linoleic acid-enriched butter fat alters mammary gland morphogenesis and reduces cancer risk in rats. J. Nutr. 129:2135-2142.[Abstract/Free Full Text]

9. Banni, S., Angioni, E., Murru, E., Carta, G., Melis, M. P., Bauman, D. E., Dong, Y. & Ip, C. (2001) Vaccenic acid feeding increases tissue levels of conjugated linoleic acid and suppresses development of premalignant lesions in rat mammary gland. Nutr. Cancer 41:91-97.[Medline]

10. Corl, B. A., Barbano, D. M., Bauman, D. E. & Ip, C. (2003) cis-9, trans-11 CLA derived endogenously from trans-11 18:1 reduces cancer risk in rats. J. Nutr. 133:2893-2900.[Abstract/Free Full Text]

11. Gomez, F. E., Bauman, D. E., Ntambi, J. M. & Fox, B. G. (2003) Effects of sterculic acid on stearoyl-CoA desaturase in differentiating 3T3–L1 adipocytes. Biochem. Biophys. Res. Commun. 300:316-326.[Medline]

12. Jeffcoat, R. & Pollard, M. R. (1977) Studies on the inhibition of the desaturases by cyclopropenoid fatty acids. Lipids 12:480-485.[Medline]

13. Ip, C., Ip, M. M., Loftus, T., Shoemaker, S. & Shea-Eaton, W. (2000) Induction of apoptosis by conjugated linoleic acid in cultured mammary tumor cells and premalignant lesions of the rat mammary gland. Cancer Epidemiol. Biomark. Prev. 9:689-696.[Abstract/Free Full Text]

14. Bauman, D. E., Barbano, D. M., Dwyer, D. A. & Griinari, J. M. (2000) Technical note: production of butter with enhanced conjugated linoleic acid for use in biomedical studies with animal models. J. Dairy Sci. 83:2422-2425.[Abstract]

15. Russo, J., Tay, L. K. & Russo, I. H. (1982) Differentiation of the mammary gland and susceptibility to carcinogenesis. Breast Cancer Res. Treat. 2:5-73.[Medline]

16. Ip, C., Thompson, H. J. & Ganther, H. E. (2000) Selenium modulation of cell proliferation and cell cycle biomarkers in normal and premalignant cells of the rat mammary gland. Cancer Epidemiol. Biomark. Prev. 9:49-54.[Abstract/Free Full Text]

17. Hara, A. & Radin, N. S. (1978) Lipid extraction of tissues with a low-toxicity solvent. Anal. Biochem. 90:420-426.[Medline]

18. Christie, W. W. (1982) A simple procedure for the rapid transmethylation of glycerolipids and cholesteryl esters. J. Lipid Res. 23:1072-1075.[Abstract]

19. McCullagh, P. & Nelder, J. A. (1989) Generalized Linear Models 1989 Chapman and Hall London, UK.

20. Kruskal, W. H. & Wallis, W. A. (1952) Use of ranks in one criterion variance analysis. J. Am. Stat. Assoc. 47:583-621.

21. Andianaivo, A. A., Siess, M.-H. & Gaydou, E. M. (1995) Modifications of hepatic drug metabolizing enzyme activities in rats fed Baobab seed oil containing cyclopropenoid fatty acids. Food Chem. Toxicol. 33:377-382.[Medline]

22. Cao, J., Blond, J.-P. & Bezard, J. (1993) Inhibition of fatty acid delta-6 and delta-5 desaturase by cyclopropene fatty acids in rat liver microsomes. Biochim. Biophys. Acta 1210:27-34.[Medline]

23. Eisele, T. A., Loveland, P. M., Kruk, D. L., Meyers, T. R., Sinnhuber, R. O. & Nixon, J. E. (1982) Effect of cyclopropenoid fatty acids on the hepatic microsomal mixed-function-oxidase system and aflatoxin metabolism in rabbits. Food Chem. Toxicol. 20:407-412.[Medline]

24. Nixon, J. E., Eisele, T. A., Wales, J. H. & Sinnhuber, R. O. (1974) Effect of subacute toxic levels of dietary cyclopropenoid fatty acids upon membrane function and fatty acid composition in the rat. Lipids 9:314-321.[Medline]

25. Ntambi, J. M. & Miyazaki, M. (2004) Regulation of stearoyl-CoA desaturases and role in metabolism. Prog. Lipid Res. 43:91-104.[Medline]

26. Griinari, J. M. & Bauman, D. E. (1999) Biosynthesis of conjugated linoleic acid and its incorporation into meat and milk in ruminants. Yurawecz, M. P. Mossoba, M. M. Kramer, J.K.G. Pariza, M. W. Nelson, G. eds. Advances in Conjugated Linoleic Acid Research 1:180-200 AOCS Press Champaign, IL. .

27. Harfoot, C. G. & Hazlewood, G. P. (1997) Lipid metabolism in the rumen. Hobson, P. N. Stewart, D. S. eds. The Rumen Microbial Ecosystem 2nd ed. 1997:382-426 Chapman and Hall London, UK. .

28. Santora, J. E., Palmquist, D. L. & Roehrig, K. L. (2000) trans-Vaccenic acid is desaturated to conjugated linoleic acid in mice. J. Nutr. 130:208-215.[Abstract/Free Full Text]

29. Glaser, K. R., Wenk, C. & Scheeder, M.R.L. (2002) Effects of feeding pigs increasing levels of C18:1 trans fatty acids on fatty acid composition of backfat and intramuscular fat as well as backfat firmness. Arch. Anim. Nutr. 56:117-130.

30. Adlof, R. O., Duval, S. & Emken, E. A. (2000) Biosynthesis of conjugated linoleic acid in humans. Lipids 35:131-135.[Medline]

31. Salminen, I., Mutanen, M., Jauhiainen, M. & Aro, A. (1998) Dietary trans fatty acids increase conjugated linoleic acid levels in human serum. J. Nutr. Biochem. 9:93-98.

32. Turpeinen, A. M., Mutanen, M., Aro, A., Salminen, I., Basu, S., Palmquist, D. L. & Griinari, J. M. (2002) Bioconversion of vaccenic acid to conjugated linoleic acid in humans. Am. J. Clin. Nutr. 76:504-510.[Abstract/Free Full Text]

33. Williams, C. M. (2000) Dietary fatty acids and human health. Ann. Zootech. 49:165-180.

34. Institute of Medicine, Food and Nutrition Board (2002) Letter report on dietary reference intakes for trans fatty acids 2002 National Academy of Science Washington, DC.

35. Craig-Schmidt, M. C. (1998) Worldwide consumption of trans fatty acids. Sébédio, J.-L. Christie, W. W. eds. trans Fatty Acids in Human Nutrition 1998:59-114 Oily Press Dundee, Scotland. .

36. Emken, E. A. (1995) trans Fatty acids and coronary heart disease risk: physicochemical properties, intake, and metabolism. Am. J. Clin. Nutr. 62:659S-669S.[Free Full Text]

37. Parodi, P. W. (1997) Cows’ milk fat components as potential anticarcinogenic agents. J. Nutr. 127:1055-1060.[Abstract/Free Full Text]

38. Bauman, D. E., Baumgard, L. H., Corl, B. A. & Griinari, J. M. (2001) Conjugated linoleic acid (CLA) and the dairy cow. Garnsworthy, P. C. Wiseman, J. eds. Recent Advances in Animal Nutrition 2001 2001:221-250 Nottingham University Press Nottingham, UK. .

39. Stanton, C., Murphy, J., McGrath, E. & Devery, R. (2003) Animal feeding strategies for conjugated linoleic acid enrichment of milk. Sebedio, J.-L. Christie, W. W. Adlof, R. O eds. Advances in Conjugated Linoleic Acid Research 2:123-145 AOCS Press Champaign, IL. .

40. Lynch, J. M., Lock, A. L., Dwyer, D. A., Norbaksh, R., Barbano, D. M. & Bauman, D. E. (2004) Flavor and stability of pasteurized milk with elevated levels of conjugated linoleic acid and vaccenic acid. J. Dairy Sci. (abst.) (in press).




This article has been cited by other articles:


Home page
 J. Nutr.Home page
Y. Wang, M. M. Jacome-Sosa, M. R. Ruth, S. D. Goruk, M. J. Reaney, D. R. Glimm, D. C. Wright, D. F. Vine, C. J. Field, and S. D. Proctor
Trans-11 Vaccenic Acid Reduces Hepatic Lipogenesis and Chylomicron Secretion in JCR:LA-cp Rats
J. Nutr., November 1, 2009; 139(11): 2049 - 2054.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
A.-L. Tardy, C. Giraudet, P. Rousset, J.-P. Rigaudiere, B. Laillet, S. Chalancon, J. Salles, O. Loreau, J.-M. Chardigny, and B. Morio
Effects of trans MUFA from dairy and industrial sources on muscle mitochondrial function and insulin sensitivity
J. Lipid Res., July 1, 2008; 49(7): 1445 - 1455.
[Abstract] [Full Text] [PDF]

Home page
 J DAIRY SCIHome page
B. Vlaeminck, G. Mengistu, V. Fievez, L. de Jonge, and J. Dijkstra
Effect of In Vitro Docosahexaenoic Acid Supplementation to Marine Algae-Adapted and Unadapted Rumen Inoculum on the Biohydrogenation of Unsaturated Fatty Acids in Freeze-Dried Grass
J Dairy Sci, March 1, 2008; 91(3): 1122 - 1132.
[Abstract] [Full Text] [PDF]

Home page
 J DAIRY SCIHome page
C. Cruz-Hernandez, J. K. G. Kramer, J. J. Kennelly, D. R. Glimm, B. M. Sorensen, E. K. Okine, L. A. Goonewardene, and R. J. Weselake
Evaluating the Conjugated Linoleic Acid and Trans 18:1 Isomers in Milk Fat of Dairy Cows Fed Increasing Amounts of Sunflower Oil and a Constant Level of Fish Oil
J Dairy Sci, August 1, 2007; 90(8): 3786 - 3801.
[Abstract] [Full Text] [PDF]

Home page
 J DAIRY SCIHome page
B. Moioli, G. Contarini, A. Avalli, G. Catillo, L. Orru, G. De Matteis, G. Masoero, and F. Napolitano
Short Communication: Effect of Stearoyl-Coenzyme A Desaturase Polymorphism on Fatty Acid Composition of Milk
J Dairy Sci, July 1, 2007; 90(7): 3553 - 3558.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
E. E. Mosley, M. K. McGuire, J. E. Williams, and M. A. McGuire
Cis-9, Trans-11 Conjugated Linoleic Acid Is Synthesized from Vaccenic Acid in Lactating Women
J. Nutr., September 1, 2006; 136(9): 2297 - 2301.
[Abstract] [Full Text] [PDF]

Home page
 J DAIRY SCIHome page
A. L. Lock, B. M. Teles, J. W. Perfield II, D. E. Bauman, and L. A. Sinclair
A Conjugated Linoleic Acid Supplement Containing trans-10, cis-12 Reduces Milk Fat Synthesis in Lactating Sheep
J Dairy Sci, May 1, 2006; 89(5): 1525 - 1532.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
J. Kraft, L. Hanske, P. Mockel, S. Zimmermann, A. Hartl, J. K. G. Kramer, and G. Jahreis
The Conversion Efficiency of trans-11 and trans-12 18:1 by {Delta}9-Desaturation Differs in Rats
J. Nutr., May 1, 2006; 136(5): 1209 - 1214.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
S. Tricon, G. C Burdge, E. L Jones, J. J Russell, S. El-Khazen, E. Moretti, W. L Hall, A. B Gerry, D. S Leake, R. F Grimble, et al.
Effects of dairy products naturally enriched with cis-9,trans-11 conjugated linoleic acid on the blood lipid profile in healthy middle-aged men.
Am. J. Clinical Nutrition, April 1, 2006; 83(4): 744 - 753.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
A. L. Lock, C. A. M. Horne, D. E. Bauman, and A. M. Salter
Butter Naturally Enriched in Conjugated Linoleic Acid and Vaccenic Acid Alters Tissue Fatty Acids and Improves the Plasma Lipoprotein Profile in Cholesterol-Fed Hamsters
J. Nutr., August 1, 2005; 135(8): 1934 - 1939.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lock, A. L.
Right arrow Articles by Ip, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lock, A. L.
Right arrow Articles by Ip, C.

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2004 by American Society for Nutrition