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De Cuyper A, Winkler D, Tütken T, Janssens GPJ, Clauss M. Fatty Acids of Microbial Origin in the Perirenal Fat of Rats (Rattus norvegicus domestica) and Guinea Pigs (Cavia porcellus) Fed Various Diets. Lipids 2020; 55:341-351. [PMID: 32343435 DOI: 10.1002/lipd.12240] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/13/2020] [Accepted: 04/05/2020] [Indexed: 11/08/2022]
Abstract
Guinea pigs are assumed to practice caecotrophy to a higher degree than rats. Studies from leporids suggest that through the practice of caecotrophy, hindgut fermenting species could build up microbial fatty acids (FA) in body tissues. We hypothesized that microbial FA would be detectable in the body tissue of guinea pigs and rats, and this to a higher degree in guinea pigs. Twenty-four rats and guinea pigs were fed with four different pelleted diets (lucerne-, meat-, meat-bone-, insect-based) in groups of six animals for 8 weeks. Perirenal adipose tissue differed in FA composition between the species in spite of the common diets. FA typically associated with microbial activity (saturated FA (SFA; typically 18:0), monounsaturated FA (MUFA; typically trans-fatty acids TFA), and odd- and branched-chain FA (Iso-FA)), were all detected. Guinea pigs had higher SFA levels than rats except on the lucerne diet. Concentrations of 18:0 were higher for guinea pigs on the meat and bone diet. Iso-FA concentrations in guinea pigs exceeded those of rats on all diets. FA profiles with a microbial fingerprint appear-although in low proportions-in the body tissue of both species, and this seemingly to a higher extent in guinea pigs. With respect to whether consumption of rodent meat rich in microbial FA has particular effects on human health as shown for ruminant products, microbial FA concentrations are probably too low to cause any distinct effects.
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Affiliation(s)
- Annelies De Cuyper
- Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Daniela Winkler
- Applied and Analytical Palaeontology, Institute of Geosciences, Johannes Gutenberg University, J.-J.-Becher-Weg 21, Mainz, 55128, Germany
| | - Thomas Tütken
- Applied and Analytical Palaeontology, Institute of Geosciences, Johannes Gutenberg University, J.-J.-Becher-Weg 21, Mainz, 55128, Germany
| | - Geert P J Janssens
- Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Marcus Clauss
- Clinic for Zoo Animals, Exotic Pets and Wildlife, Vetsuisse Faculty, University of Zurich, Winterthurerstr. 260, Zurich, 8057, Switzerland
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Ecballium elaterium (L.) A. Rich. seed oil: Chemical composition and antiproliferative effect on human colonic adenocarcinoma and fibrosarcoma cancer cell lines. ARAB J CHEM 2019. [DOI: 10.1016/j.arabjc.2015.02.023] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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Natural CLA-Enriched Lamb Meat Fat Modifies Tissue Fatty Acid Profile and Increases n-3 HUFA Score in Obese Zucker Rats. Biomolecules 2019; 9:biom9110751. [PMID: 31752405 PMCID: PMC6921071 DOI: 10.3390/biom9110751] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 11/13/2019] [Accepted: 11/17/2019] [Indexed: 12/11/2022] Open
Abstract
Ruminant fats are characterized by different levels of conjugated linoleic acid (CLA) and α-linolenic acid (18:3n-3, ALA), according to animal diet. Tissue fatty acids and their N-acylethanolamides were analyzed in male obese Zucker rats fed diets containing lamb meat fat with different fatty acid profiles: (A) enriched in CLA; (B) enriched in ALA and low in CLA; (C) low in ALA and CLA; and one containing a mixture of olive and corn oils: (D) high in linoleic acid (18:2n-6, LA) and ALA, in order to evaluate early lipid metabolism markers. No changes in body and liver weights were observed. CLA and ALA were incorporated into most tissues, mirroring the dietary content; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increased according to dietary ALA, which was strongly influenced by CLA. The n-3 highly-unsaturated fatty acid (HUFA) score, biomarker of the n-3/n-6 fatty acid ratio, was increased in tissues of rats fed animal fats high in CLA and/or ALA compared to those fed vegetable fat. DHA and CLA were associated with a significant increase in oleoylethanolamide and decrease in anandamide in subcutaneous fat. The results showed that meat fat nutritional values are strongly influenced by their CLA and ALA contents, modulating the tissue n-3 HUFA score.
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Aidi Wannes W, Saidani Tounsi M, Marzouk B. A review of Tunisian medicinal plants with anticancer activity. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2017; 15:/j/jcim.ahead-of-print/jcim-2017-0052/jcim-2017-0052.xml. [PMID: 28915116 DOI: 10.1515/jcim-2017-0052] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Accepted: 06/06/2017] [Indexed: 06/07/2023]
Abstract
Cancer is a major public health problem in the world. The use of the medicinal plants in cancer prevention and management is frequent in Africa, especially in Tunisia, and it is transmitted from generation to generation within cultures. Many previous studies showed that a wide range of Tunisian medicinal plants exerted cytotoxic and anticancer activity. A comprehensive review was conducted to collect information from scientific journal articles, including indigenous knowledge researches, about Tunisian medicinal plants used for the prevention and management of cancer. The aim of this review article is to provide the reader with information concerning the importance of Tunisian medicinal plants in the prevention and management of cancer and to open the door for the health professionals and scientists working in the field of pharmacology and therapeutics to produce new drug formulations to treat different types of cancer.
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Affiliation(s)
- Wissem Aidi Wannes
- Laboratory of Aromatic and Medicinal Plants, Biotechnologic Center Borj-Cedria Technopark, Hammam-Lif, Tunisia
| | - Moufida Saidani Tounsi
- Laboratory of Aromatic and Medicinal Plants, Biotechnologic Center Borj-Cedria Technopark, Hammam-Lif, Tunisia
| | - Brahim Marzouk
- Laboratory of Aromatic and Medicinal Plants, Biotechnologic Center Borj-Cedria Technopark, Hammam-Lif, Tunisia
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Effect of double-muscling in Belgian Blue young bulls on the intramuscular fatty acid composition with emphasis on conjugated linoleic acid and polyunsaturated fatty acids. ACTA ACUST UNITED AC 2016. [DOI: 10.1017/s1357729800058227] [Citation(s) in RCA: 190] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
AbstractThe effect of double-muscling (DM) genotype (double-muscling, mh/mh; heterozygous, mh/+; normal, +/+) of Belgian Blue (BB) young bulls on the intramuscular fatty acid composition, in particular conjugated linoleic acid (CLA) and polyunsaturated fatty acids (PUFA) was examined in five different muscles. The relative fatty acid composition showed only minor differences between muscles within genotypes. However, the DM genotype had a large effect on both the intramuscular total fatty acid content and on the relative fatty acid composition. Across muscles, the mh/mh animals had a lower total fatty acid content compared with the +/+animals (907 v: 2656 mg/100 g muscle;P< 0·01) and a higher PUFA proportion in total fatty acids (27·5 v 11·3 g/100 g total fatty acids;P< 0001), resulting in a higher PUFA/saturated fatty acid ratio (0·55 v 0·18;P< 0·01) and a lower n-6/n-3 ratio (5·34 v. 6·17;P< 0·01). The heterozygous genotype was intermediate between the two homozygous genotypes. The relative CLA content was similar in the mh/mh and +/+ genotypes and approximated 0·4 to 0·5 g/100 g total fatty acids. From the data it is further suggested that differences in the metabolism of the n-3 and n-6 fatty acids could exist between DM genotypes.
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Hussain SKA, Srivastava A, Tyagi A, Shandilya UK, Kumar A, Kumar S, Panwar S, Tyagi AK. Characterization of CLA-producing Butyrivibrio spp. reveals strain-specific variations. 3 Biotech 2016; 6:90. [PMID: 28330160 PMCID: PMC4786556 DOI: 10.1007/s13205-016-0401-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2015] [Accepted: 01/22/2016] [Indexed: 01/18/2023] Open
Abstract
Conjugated Linoleic Acid (CLA), a fatty acid with high nutraceutical value is produced in rumen by resident bacterial species, especially Butyrivibrio spp. The present study was undertaken to examine the diversity of indigenous Butyrivibrio spp. from rumen liquor of Indian ruminants. The isolates were screened for their CLA production capability at different level of linoleic acid (LA) (0, 200, 400, 600, 800 μg/ml) at different time intervals (0, 2, 4, 6, 12, and 24 h). A total of more than 300 anaerobic cultures were isolated and 31 of them were identified as Butyrivibrio spp. based on morphological, biochemical and molecular characterization. Further, molecular characterization revealed that a large portion (67.7 %) of isolated Butyrivibrio belonged to Butyrivibrio fibrisolvens (B. fibrisolvens) species which is considered to be the most active bacteria amongst the rumen bacteria populace in terms of CLA production. Bacterial isolate VIII (strain 4a) showed highest CLA production ability (140.77 μg/ml) when incubated at 200 μg/ml LA for 2 h, which is 240 % higher than the isolate XXVII, Butyrivibrio proteoclasticus (B. proteoclasticus) showing lowest CLA production (57.28 μg/ml) amongst the screened isolates. It was evident from the observations recorded during the course of experiments that CLA production ability is strain specific and thus did not follow a single pattern. CLA production also varied with time of incubation and concentration of free linoleic acid supplemented in the growth medium. The results of these findings put forward a strain that is high CLA producer and can be further exploited as an additive for enhancing meat and milk quality in ruminants.
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Affiliation(s)
- S K Asraf Hussain
- Dairy Cattle Nutrition Division, National Dairy Research Institute, Karnal, 132001, Haryana, India
| | - Anima Srivastava
- Dairy Cattle Nutrition Division, National Dairy Research Institute, Karnal, 132001, Haryana, India
| | - Ashish Tyagi
- Dairy Cattle Nutrition Division, National Dairy Research Institute, Karnal, 132001, Haryana, India
| | - Umesh Kumar Shandilya
- Dairy Cattle Nutrition Division, National Dairy Research Institute, Karnal, 132001, Haryana, India
| | - Ashwani Kumar
- Seth Jai Parkash Mukand Lal Institute of Engineering and Technology (JMIT), Radaur, 135133, Haryana, India
- Department of Nutrition Biology, Central University of Haryana, Mahendergarh, 123029, Haryana, India
| | - Sachin Kumar
- Dairy Cattle Nutrition Division, National Dairy Research Institute, Karnal, 132001, Haryana, India
| | - Surbhi Panwar
- Seth Jai Parkash Mukand Lal Institute of Engineering and Technology (JMIT), Radaur, 135133, Haryana, India
| | - Amrish Kumar Tyagi
- Dairy Cattle Nutrition Division, National Dairy Research Institute, Karnal, 132001, Haryana, India.
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Relationship between stearoyl-CoA desaturase 1 gene expression, relative protein abundance, and its fatty acid products in bovine tissues. J DAIRY RES 2014; 81:333-9. [PMID: 24904960 DOI: 10.1017/s0022029914000181] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Stearoyl-CoA desaturase 1 (SCD1) greatly contributes to the unsaturated fatty acids present in milk and meat of cattle. The SCD1 enzyme introduces a double bond into certain saturated fatty acyl-CoAs producing monounsaturated fatty acids (MUFA). The SCD1 enzyme also has been shown to be active in the bovine mammary gland converting t11 18:1 (vaccenic acid) to c9 t11 conjugated linoleic acid (CLA). The objective of this study was to determine any association between the gene expression of SCD1 and occurrence of its products (c9 14:1, c9 16:1, c9 18:1, and c9 t11 18:2) in various bovine tissues. Tissue samples were obtained from lactating Holstein cows (n=28) at slaughter, frozen in liquid nitrogen and stored at -80 °C. Total RNA was extracted and converted to complementary DNA for quantitative real time polymerase chain reaction (PCR) analysis of the SCD1 gene. Extracted lipid was converted to fatty acid methyl esters and analysed by GC. Tissues varied in expression of SCD1 gene with mammary, cardiac, intestinal adipose, and skeletal muscle expressing greater copy number as compared with lung, large intestine, small intestine and liver (371, 369, 328, 286, 257, 145, 73, and 21 copies/ng RNA, respectively). Tissues with high mRNA expression of SCD1 contained greater SCD1 protein whereas detection of SCD1 protein in tissues with low SCD1 mRNA expression was very faint or absent. Across tissues, the desaturase indices for c9 18:1 (r=0.24) and sum of SCD products (r=0.20) were positively correlated with SCD1 gene expression (P<0.01 for both). Within each tissue, the relationship between SCD1 gene expression and the desaturase indices varied. No correlation was detected between SCD1 expression and desaturase indices in the liver, large and small intestines, lung, cardiac or skeletal muscles. Positive correlations, however, were detected between SCD1 expression and the desaturase indices in intestinal adipose tissue (P<0.02 for all) except 14:1, whereas only c9 18:1, c9 t11 18:2 and sum of all desaturase indices were positively correlated with SCD1 expression in mammary tissue (P < or = 0.03). Overall, the relationship between SCD1 gene expression and occurrence of its products seems to be tissue specific.
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Zheng M, Falkeborg M, Zheng Y, Yang T, Xu X. Formulation and characterization of nanostructured lipid carriers containing a mixed lipids core. Colloids Surf A Physicochem Eng Asp 2013. [DOI: 10.1016/j.colsurfa.2013.03.070] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Werner LB, Hellgren LI, Raff M, Jensen SK, Petersen RA, Drachmann T, Tholstrup T. Effects of butter from mountain-pasture grazing cows on risk markers of the metabolic syndrome compared with conventional Danish butter: a randomized controlled study. Lipids Health Dis 2013; 12:99. [PMID: 23842081 PMCID: PMC3720277 DOI: 10.1186/1476-511x-12-99] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2013] [Accepted: 06/28/2013] [Indexed: 11/27/2022] Open
Abstract
Background There is considerable interest in dairy products from low-input systems, such as mountain-pasture grazing cows, because these products are believed to be healthier than products from high-input conventional systems. This may be due to a higher content of bioactive components, such as phytanic acid, a PPAR-agonist derived from chlorophyll. However, the effects of such products on human health have been poorly investigated. Objective To compare the effect of milk-fat from mountain-pasture grazing cows (G) and conventionally fed cows (C) on risk markers of the metabolic syndrome. Design In a double-blind, randomized, 12-week, parallel intervention study, 38 healthy subjects replaced part of their habitual dietary fat intake with 39 g fat from test butter made from milk from mountain-pasture grazing cows or from cows fed conventional winter fodder. Glucose-tolerance and circulating risk markers were analysed before and after the intervention. Results No differences in blood lipids, lipoproteins, hsCRP, insulin, glucose or glucose-tolerance were observed. Interestingly, strong correlations between phytanic acid at baseline and total (P<0.0001) and LDL cholesterol (P=0.0001) were observed. Conclusions Lack of effects on blood lipids and inflammation indicates that dairy products from mountain-pasture grazing cows are not healthier than products from high-input conventional systems. Considering the strong correlation between LDL cholesterol and phytanic acid at baseline, it may be suggested that phytanic acid increases total and LDL cholesterol. Trial registration ClinicalTrials.gov, NCT01343589
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Affiliation(s)
- Louise B Werner
- Department of Nutrition, Exercise and Sports, Faculty of Sciences, University of Copenhagen, Frederiksberg 1958, Denmark.
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Liu JR, Chen BQ, Yang YM, Han XH, Xue YB, Wang XL, Zheng YM, Liu RH. Effects ofcis-9,trans-11-conjugated linoleic acid on cancer cell cycle. Environ Health Prev Med 2012. [PMID: 21432279 DOI: 10.1007/s11670-002-0021-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES To determine the effect of cis-9, trans-11-conjugated linoleic acid on the cell cycle of mammary cancer cells (MCF-7) and its possible mechanism of inhibition cancer growth. METHODS Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B(1), D(1), p16(ink4a) and p21(cip/wafl) of MCF-7 cells which were treated with various c9, t11-CLA concentrations (25 mM, 50 mM, 100 mM and 200 mM) of c9, t11-CLA for 24 and 48 h, with negative controls (0.1% ethanol). RESULTS The cell growth and DNA synthesis of MCF-7 cells were inhibited by c9, t11-CLA. MCF-7 cells, after treatment with various c9, t11-CLA doses mentioned above for 8 days, the inhibition frequency was 27.18%, 35.43%, 91.05%, and 92.86%, respectively and the inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 mM, 24 h) incorporated significantly less(3)H-TdR than did the negative control (P<0.05 andP<0.01). To further investigate the influence on the cell cycle progression, we found that c9, t11-CLA may arrest the cell cycle of MCF-7 cells. Immunocytochemical staining demonstrated that MCF-7 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA, and Cyclin, A, B(1), D(1) compared with the negative controls (P<0.01), whereas the expressions of p16(ink4a) and p21(cip/wafl), cyclin-dependent kinases inhibitors (CDKI), were increased. CONCLUSIONS The cell growth and proliferation of MCF-7 cells is inhibited by c9, t11-CLA by blocking the cell cycle, which reduces expressions of cyclin A, B(1), D(1) and enhances expressions of CDKI (p16(ink4a) and p21(cip/wafl)).
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Affiliation(s)
- Jia Ren Liu
- Public Health College of Harbin Medical University, 199 Dongdazhi Street, Nangang District, Harbin, Heilongijang, P.R. China,
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Ross GR, Van Nieuwenhove CP, González SN. Fatty acid profile of pig meat after probiotic administration. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:5974-5978. [PMID: 22506842 DOI: 10.1021/jf205360h] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
The aim of this work was to study the fatty acid profile of pig meat after probiotic administration. Thirty postweaned pigs (25 day old) were distributed into 2 groups: control (n = 15) and probiotic (n = 15). Each experimental group was fed ad libitum on a commercial diet for 35 days. Lactobacillus amylovorus and Enterococcus faecium mixed culture (10(8) CFU/ml)was daily orally delivered to the probiotic group. At the end of the assay, six pigs randomly selected from each group were slaughtered and muscle samples (Longissimus dorsi) were taken for fatty acid analysis. Tissues from the probiotic group animals exhibited an increase in monounsaturated and polyunsaturated fatty acids; furthermore, linoleic acid (C18:2), linolenic acid (18:3), and cis-9,trans-11 conjugated linoleic acid (CLA) concentrations were significantly higher (p < 0.05) compared to the control group. These results suggest probiotic administration could be useful to modify and improve the fatty acid profile of pig meat.
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Affiliation(s)
- Gloria Romina Ross
- Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán-CONICET , Ayacucho 471, 4000-Tucumán, Argentina
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Andreoli MF, Martinelli MI, Scalerandi MV, Fariña AC, Williner MR, Bernal CA. CLA prevents alterations in glycolytic metabolites induced by a high fat diet. EUR J LIPID SCI TECH 2012. [DOI: 10.1002/ejlt.201100182] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Selectively Hydrogenated Soybean Oil Exerts Strong Anti-Prostate Cancer Activities. Lipids 2010; 46:287-95. [DOI: 10.1007/s11745-010-3495-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2010] [Accepted: 10/19/2010] [Indexed: 10/18/2022]
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Conjugated linoleic acid reduces hepatic steatosis and restores liver triacylglycerol secretion and the fatty acid profile during protein repletion in rats. Lipids 2010; 45:1035-45. [PMID: 20853155 DOI: 10.1007/s11745-010-3466-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2010] [Accepted: 08/18/2010] [Indexed: 11/27/2022]
Abstract
Protein depletion is associated with hepatic steatosis and decreased circulating triacylglycerol (TAG). Since conjugated linoleic acid (CLA) increases lean body mass, protects against muscle catabolism, and modulates lipid metabolism, the aim of this work was to investigate the effects of CLA with two different amounts of dietary fat on the regulation of plasma and hepatic TAG concentration, and its possible connections with changes in fatty acid (FA) profile in plasma, liver and adipose tissue and hepatic oxidative status during protein repletion. Rats were fed a low protein diet (14 days) and then a protein repletion diet (30 days), supplemented or not with CLA, containing 7% (w/w) or 20% (w/w) of fat. Hepatic TAG secretion and removal by muscle and adipose tissue lipoprotein lipase, FA profile and liver oxidative status were evaluated. Protein depletion affected hepatic TAG secretion and peripheral removal, decreasing plasma and increasing liver TAG concentration, whereas protein repletion with CLA improved these abnormalities independently of the amount of dietary fat by increasing hepatic TAG secretion. This prevention in the absence of CLA was not observed. CLA was incorporated in plasma and tissues (adipose > liver > plasma, and c9,t11-CLA > t10,c12-CLA), accompanied by alterations in FA composition, mainly in adipose tissue. The hepatic oxidative stress was overcome by protein repletion. CLA had a beneficial impact on TAG metabolism in protein repleted animals, preventing hepatic steatosis through higher hepatic TAG secretion.
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Gaspardo B, Lavrenčič A, Levart A, Del Zotto S, Stefanon B. Use of milk fatty acids composition to discriminate area of origin of bulk milk. J Dairy Sci 2010; 93:3417-26. [DOI: 10.3168/jds.2009-2788] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2009] [Accepted: 04/19/2010] [Indexed: 11/19/2022]
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Flowers M, Schroeder JA, Borowsky AD, Besselsen DG, Thomson CA, Pandey R, Thompson PA. Pilot study on the effects of dietary conjugated linoleic acid on tumorigenesis and gene expression in PyMT transgenic mice. Carcinogenesis 2010; 31:1642-9. [PMID: 20624750 DOI: 10.1093/carcin/bgq148] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Conjugated linoleic acid (CLA) is a class of commercially available fatty acids that have been associated with anticancer properties in rodent models of chemical carcinogenesis. We conducted a pilot study to examine the antitumor effect of dietary CLA in a polyoma virus-middle T antigen (PyMT) mouse model of invasive breast cancer. Virgin 4-week-old PyMT mice were administered a mixed-isomer CLA diet (1% wt/wt) or control AIN-93G diet for 4 weeks (N = 6 and 5, respectively) and tumor burden was assessed at 8 weeks of age. Thoracic mammary glands were prepared as whole mounts with other glands being formalin fixed and paraffin embedded for histology and immunohistochemistry (IHC). Total RNA was prepared for microarray and real-time reverse transcription-polymerase chain reaction analysis. Western blots were performed for protein expression analysis. Tumor incidence was significantly increased in CLA-treated animals compared with controls (P = 0.009) and occurred with extensive lobular-alveolar expansion and loss of mammary adipose tissue. More than 100 genes were downregulated > or = 2-fold in the CLA-treated group compared with controls, including adipose-specific markers, as wells as cytoskeletal and adhesion-related genes. This was supported by dramatic decreases in the epithelial adherens E-cadherin and beta-catenin as demonstrated by IHC. Taken together, these results suggest that dietary CLA affects the mammary stromal environment, leading to tumor progression and cellular expansion in the PyMT mouse model. Further studies of the potential for cancer promotion are needed, especially because mixed-isomer CLA formulations are sold commercially as a nutritional supplement.
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Affiliation(s)
- Margaret Flowers
- Department of Experimental Therapeutics, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA.
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Kurban S, Erkoç F, Erkoç Ş. Quantum‐chemical treatment of the linoleic acid molecule and two of its conjugated isomers. EUR J LIPID SCI TECH 2009. [DOI: 10.1002/ejlt.200900046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Affiliation(s)
- Sevil Kurban
- Department of Biochemistry, Meram Faculty of Medicine, Selçuk University, Konya, Turkey
| | - Figen Erkoç
- Department of Biology Education, Gazi University, Ankara, Turkey
| | - Şakir Erkoç
- Department of Physics, Middle East Technical University, Ankara, Turkey
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Ramírez-Santana C, Castellote C, Castell M, Rivero M, Rodríguez-Palmero M, Franch A, Pérez-Cano FJ. Long-term feeding of the cis-9,trans-11 isomer of conjugated linoleic acid reinforces the specific immune response in rats. J Nutr 2009; 139:76-81. [PMID: 19056641 DOI: 10.3945/jn.108.097428] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Several effects on the immune system have been ascribed to the cis9,trans11 conjugated linoleic acid (CLA) isomer. We studied whether feeding a diet enriched with an 80:20 CLA isomer mix of cis9,trans11 and trans10,cis12 CLA from gestation to adulthood affects the capacity of adult rats to achieve a specific immune response. Pregnant Wistar rats were fed a 1% CLA diet or a control diet beginning on d 7 of gestation. Weaned pups received the same diet as dams until they were 15 wk old. Rats from both groups were immunized with ovalbumin (OVA) when they were 9 wk old. Dietary CLA enhanced splenocyte OVA-specific proliferation by approximately 50% (P < 0.05) and decreased the mitogen-induced proliferative responses of these cells by approximately 10-20% (P < 0.05). The diminished splenocyte proliferative response was accompanied by a lower interleukin-2 secretion (P < 0.05). Long-term CLA supplementation did not increase serum, spleen, or mesenteric lymph node production of OVA-specific antibodies (Ab) or the number of spleen anti-OVA Ab-secreting cells. Interestingly, dietary CLA increased intestinal anti-OVA IgA production by approximately 75% (P < 0.05). In conclusion, a 1% CLA diet administered from gestation to adulthood enhanced specific systemic cell-mediated immunity as well as the mucosal IgA immune response, whereas it downregulated the polyclonal activation of the immune system. These data support the long-term effects of dietary cis9,trans11 CLA isomer on the immune system.
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Affiliation(s)
- Carolina Ramírez-Santana
- Department of Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain E-08028
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Conjugated Linoleic Acid (CLA) inhibits new vessel growth in the mammalian brain. Brain Res 2008; 1213:35-40. [DOI: 10.1016/j.brainres.2008.01.096] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2007] [Revised: 01/24/2008] [Accepted: 01/25/2008] [Indexed: 11/17/2022]
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20
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Watkins B, Li Y. Conjugated Linoleic Acids. FOOD SCIENCE AND TECHNOLOGY 2008. [DOI: 10.1201/9781420046649.ch23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Tsuzuki T, Kawakami Y. Tumor angiogenesis suppression by α-eleostearic acid, a linolenic acid isomer with a conjugated triene system, via peroxisome proliferator-activated receptor γ. Carcinogenesis 2008; 29:797-806. [DOI: 10.1093/carcin/bgm298] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
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Liguori A, D'Armiento FP, Palagiano A, Balestrieri ML, Williams-Ignarro S, de Nigris F, Lerman LO, D'Amora M, Rienzo M, Fiorito C, Ignarro LJ, Palinski W, Napoli C. Effect of gestational hypercholesterolaemia on omental vasoreactivity, placental enzyme activity and transplacental passage of normal and oxidised fatty acids. BJOG 2007; 114:1547-56. [PMID: 17903226 DOI: 10.1111/j.1471-0528.2007.01510.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE Maternal hypercholesterolaemia during pregnancy increases lipid peroxidation in mothers and fetuses and programs increased susceptibility to atherosclerosis later in life. The objective of this study was to elucidate the role of the placenta in mediating oxidative stress from mother to offspring. DESIGN Comparison between normo- and hypercholesterolaemic mothers (n = 36 each) and their children. SETTING Obstetric wards, hospitals of the University of Naples and Regione Campania. POPULATION Healthy primiparas delivering by caesarean section. METHODS Biochemical measurements of oxidative stress and serum leptin in cord plasma and placenta, immunochemistry of placenta microvessels, and vasoreactivity studies were performed. MAIN OUTCOME MEASURES Oxidative status (i.e. lipid composition and content of oxidised fatty acids, activity of pro- and antioxidant enzymes, immunohistochemical presence of oxidation-specific epitopes) in maternal and cord blood and in placental tissue, as well as vascular reactivity in omental arteries. RESULTS Hypercholesterolaemia during pregnancy was associated with extensive changes in fatty acid composition of both maternal and cord blood lipids, sufficient to alter vasoreactivity of omental vessels. Results also indicated that the placenta is not only subject to substantial oxidative stress, but that it may further increase fetal oxidative stress through changes of pro- and antioxidant enzyme activities. CONCLUSIONS The placenta plays an important role in both transmitting and enhancing pathogenic effects of gestational hypercholesterolaemia.
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Affiliation(s)
- A Liguori
- Regional Hospital of Pellegrini, Department of Medicine and Division of Cardiology-CCU, ASLNA1, Naples 80100, Italy
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Gerber M, Razanamahefa L, Bougnoux P. Trans fatty acids and cancers: AFSSA recommendations. EUR J LIPID SCI TECH 2007. [DOI: 10.1002/ejlt.200600280] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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Abstract
Conjugated linoleic acid (CLA) is a collective term for positional and geometric isomers of octadecadienoic acid in which the double bonds are conjugated, i.e. contiguous. CLA was identified as a component of milk and dairy products over 20 years ago. It is formed as an intermediate in the course of the conversion of linoleic acid to oleic acid in the rumen. The predominant naturally occurring isomer is the cis-9, trans-11 modification. Treatment of linoleic acid-rich oils such as safflower oil, soyabean oil, or maize oil with base and heat will result in the formation of CLA. Two isomers predominate in the synthetic preparation, c9,t11 and t10,c12. CLA has been shown to inhibit chemically-induced skin, stomach, mammary or colon tumours in mice and rats. The inhibition of mammary tumours in rats is effective regardless of type of carcinogen or type or amount of dietary fat. CLA has also been shown to inhibit cholesterol-induced atherosclerosis in rabbits. When young animals (mice, pigs) are placed on CLA-containing diets after weaning they accumulate more body protein and less fat. Since CLA is derived from the milk of ruminant animals and is found primarily in their meat and in products derived from their milk there is a concerted world-wide effort to increase CLA content of milk by dietary means. Its effect on growth (less fat, more protein) is also a subject of active research. The mechanisms underlying the effects of CLA are still moot.
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KUMAR VVIJAY, SHARMA VIVEK, BECTOR BS. Effect of ripening on total conjugated linoleic acid and its isomers in buffalo Cheddar cheese. INT J DAIRY TECHNOL 2006. [DOI: 10.1111/j.1471-0307.2006.00274.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Fukuda S, Suzuki Y, Murai M, Asanuma N, Hino T. Isolation of a novel strain of Butyrivibrio fibrisolvens that isomerizes linoleic acid to conjugated linoleic acid without hydrogenation, and its utilization as a probiotic for animals. J Appl Microbiol 2006; 100:787-94. [PMID: 16553734 DOI: 10.1111/j.1365-2672.2006.02864.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
AIM Isolation of a new strain of Butyrivibrio fibrisolvens possessing great capacity to produce conjugated linoleic acid (CLA) in order to utilize as a probiotic for animals. METHODS AND RESULTS A novel strain (MDT-5) was isolated from the goat rumen, which exclusively converted linoleic acid (LA) to CLA, because of its high LA isomerase activity with virtually no CLA reductase activity. MDT-5 also converted linolenic acid to conjugated linolenic acid that may be more bioactive than CLA. The oral administration of MDT-5 every other day to mice for 2 weeks resulted in increased amounts of CLA in the contents of the large intestine (2.5-fold), as well as in adipose tissue (threefold). Feeding a high-LA diet, as well as prolonging the period of MDT-5 administration, further increased the CLA content in body fat. CONCLUSIONS MDT-5 has by far greater ability to produce CLA than any other known bacteria. Administration of MDT-5 to mice increases CLA production in the large intestine, which results in increased CLA absorption. SIGNIFICANCE AND IMPACT OF THE STUDY MDT-5 may be useful in pet animals as a probiotic to provide CLA continuously.
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Affiliation(s)
- S Fukuda
- Department of Life Science, Meiji University, Kawasaki, Japan
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27
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Raff M, Tholstrup T, Sejrsen K, Straarup EM, Wiinberg N. Diets rich in conjugated linoleic acid and vaccenic acid have no effect on blood pressure and isobaric arterial elasticity in healthy young men. J Nutr 2006; 136:992-7. [PMID: 16549463 DOI: 10.1093/jn/136.4.992] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
The objective of this study was to examine the effect on blood pressure (BP) and isobaric arterial elasticity (AE), as a measure of arterial health, of a commercial mixture of conjugated linoleic acids (CLA) and of milk fat produced through livestock feeding to have a high content of vaccenic acid (VA). Healthy young men (n = 60) with a BMI of 22.5 +/- 2 kg/m2 (mean +/- SD) participated in this double-blind, randomized, 5-wk, parallel intervention study. The participants substituted 115 g of their daily fat intake with fat from 1 of 3 test diets: 1) CLA-diet rich in CLA (4.7 g/d of c9,t11- and t10,c12-CLA isomers in equal amounts); 2) VA-diet rich in VA (3.6 g/d); or 3) C-diet, a control diet with a low content of VA and CLA. All test diets were based on milk fat. BP and AE (measured by an oscillometric method) were measured before and after the intervention period. The effects of the test diets did not differ on any outcome variable: e.g., systolic- and diastolic blood pressure (SBP and DBP), pulse pressure (PP), isobaric arterial compliance (AC), distensibility (AD), or volume (AV). In conclusion, diets rich in milk fat and either CLA or VA have no effect on BP or AE indices in healthy young men compared with a control diet.
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Affiliation(s)
- Marianne Raff
- Department of Human Nutrition, The Royal Veterinary and Agricultural University, Frederiksberg, Denmark.
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Szölloskei G, Wagner L, Németh S, Husvéth F. In sacco studies of conjugated linoleic acid production from various oils in the rumen of sheep. Acta Vet Hung 2005; 53:411-23. [PMID: 16363143 DOI: 10.1556/avet.53.2005.4.2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
In this experiment sunflower oil, soybean oil and fish oil were incubated in rumen-fistulated adult ewes (n = 5) to study conjugated linoleic acid (CLA) production in the rumen. The individual oils were incubated in nylon bags in the rumen on perlite carrier (40% oil, 60% carrier) over a period of 2, 4, 6, 8, 10 and 12 h for all treatments. During the incubation of each oil primarily the formation of the cis-9, trans-11 isomer of CLA could be observed. Both sunflower and soybean oils showed similar changes in the rumen. After the incubation of these two vegetable oils the proportion of linoleic acid decreased significantly as the duration of incubation increased in the rumen. These changes were accompanied by a significant increase in the amount of cis-9, trans-11 CLA. However, in the case of sunflower oil the rate of formation of the cis-9, trans-11 CLA isomer was significantly higher after the different incubation times as compared to soybean oil. Much lower amounts of CLA were formed when fish oil was incubated in the rumen. The level of cis-9, trans-11 isomer produced during these treatments was 10% less than the amount obtained with the other two oils of vegetable origin. Besides the cis-9, trans-11 isomer, trans-10, cis-12 CLA could also be detected during the incubation of the different oils in the rumen. However, the level of this isomer was low and did not show consistent differences among the treatments. The results of this experiment indicate that the fatty acid composition of the oils and the duration of incubation collectively determine the amount of CLA produced in the first compartment of the forestomach of ruminants.
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Affiliation(s)
- G Szölloskei
- Department of Animal Physiology and Animal Nutrition, Georgikon Faculty of Agriculture, University of Veszprém, Hungary
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Lee KW, Lee HJ, Cho HY, Kim YJ. Role of the Conjugated Linoleic Acid in the Prevention of Cancer. Crit Rev Food Sci Nutr 2005; 45:135-44. [PMID: 15941017 DOI: 10.1080/10408690490911800] [Citation(s) in RCA: 83] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
There are multiple lines of evidence that a variety of natural fatty acids are effective in health promotion. Among these fatty acids, conjugated linoleic acid (CLA)--a collective term referring to a mixture of positional and geometric isomers of linoleic acid (LA, cis-9, cis-12-octadecadienoic acid)--is currently under intensive investigation due to its health-promotion potential. The antitumor activity of CLA is of special interest, since it shows inhibitory effects against multistage carcinogenesis at relatively low dietary levels. Many studies using in vivo and in vitro models have shown that CLA suppresses the development of multistage carcinogenesis at different sites. The research to date on CLA has provided a vast amount of information about the mechanism on how CLA functions in the prevention of cancer. This article discusses characteristics of CLA in the prevention of cancer in both in vivo and in vitro studies and the possible underlying chemoprevention mechanisms.
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Affiliation(s)
- Ki Won Lee
- Department of Food Science and Technology, School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea
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Chen BQ, Yang YM, Wang Q, Gao YH, Liu JR, Zhang JS, Wang XL, Liu RH. Effects of c9,t11-conjugated linoleic acid on adhesion of human gastric carcinoma cell line SGC-7901. World J Gastroenterol 2004; 10:1392-1396. [PMID: 15133841 PMCID: PMC4656272 DOI: 10.3748/wjg.v10.i10.1392] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2003] [Revised: 12/01/2003] [Accepted: 12/08/2003] [Indexed: 12/15/2022] Open
Abstract
AIM To investigate the effect of c9,t11-conjugated linoleic acid (c9,t11-CLA) on the adhesion of human gastric carcinoma cell line (SGC-7901). METHODS SGC-7901 cells were at first treated with different concentrations (25, 50, 100, 200 micromol/L) of c9,t11-CLA and 1 mL/L ethanol (as a negative control) for 24 h. Using adhesion assay and Western blot, we investigated the ability of SGC-7901 cells to adhere to intracellular matrix and examined the expression of E-cadherin (ECD), alpha-catenin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in these cells. RESULTS The attachment rate to laminin of SGC-7901 cells treated with different concentrations of c9,t11-CLA (0, 25, 50, 100, and 200 micromol/L) was 100.0+/-3.3, 95.7+/-4.0, 89.2+/-4.6, 87.9+/-6.1, and 65.9+/-5.8, respectively. The attachment rate to fibronectin was 100.0+/-4.7, 96.8+/-3.8, 94.5+/-4.1, 76.5+/-4.3, and 61.8+/-4.8, respectively. The attachment rate to Matrigel was 99.9+/-6.6, 91.4+/-6.8, 85.5+/-7.4, 79.3+/-5.6, and 69.6+/-5.1, respectively. Besides, c9,t11-CLA could increase the level of ECD and alpha-catenin, and decrease the level of ICAM-1 and VCAM-1 in SGC-7901 cells. CONCLUSION c9,t11-CLA can reduce the adhesion of human gastric carcinoma cells to laminin, fibronectin and Matrigel. c9,t11-CLA can increase the level of ECD and alpha-catenin, and decrease the level of ICAM-1 and VCAM-1 in human gastric carcinoma cells.
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Affiliation(s)
- Bing-Qing Chen
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
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Corl BA, Barbano DM, Bauman DE, Ip C. cis-9, trans-11 CLA derived endogenously from trans-11 18:1 reduces cancer risk in rats. J Nutr 2003; 133:2893-900. [PMID: 12949384 DOI: 10.1093/jn/133.9.2893] [Citation(s) in RCA: 137] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
The present study was designed to examine the effects of increasing dietary levels of vaccenic acid (VA) and cis-9, trans-11 conjugated linoleic acid (CLA) on chemically induced mammary carcinogenesis in rats. Both fatty acids were provided as a natural component in butter fat. The conversion of VA to CLA by delta9-desaturase was documented previously in several species, including rats and humans. Specifically, our objective was to determine the relative contribution of dietary VA and CLA to the tissue concentration of CLA and its ability to inhibit the development of mammary carcinomas. A total of 7 diets were formulated with varying levels of CLA and VA. The overall dietary treatment scheme was designed to evaluate the modulation of mammary cancer risk by 1). small increases of CLA in the presence of a low level of VA and 2). more substantial increases of VA against a background of low levels of CLA. As expected, small increases in dietary CLA at the low end of the CLA dose-response range did not reduce tumorigenesis. In contrast, there was a distinct and marked inhibitory response to VA that was dose dependent. The effect of VA was magnified in this experiment because the dose range of VA tested was much broader than that of CLA. Fatty acid analysis showed that the conversion of dietary VA to CLA resulted in a dose-dependent increase in the accumulation of CLA in the mammary fat pad, which was accompanied by a parallel decrease in tumor formation in the mammary gland. The finding confirms that the conversion of VA to CLA is as important for cancer prevention as the dietary supply of CLA. Thus, VA is also anticarcinogenic, and VA and CLA represent functional food components that are present in ruminant fat.
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Affiliation(s)
- Benjamin A Corl
- Department of Animal Science and. Department of Food Science, Cornell University, Ithaca, NY 14853, USA
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Chen BQ, Yang YM, Gao YH, Liu JR, Xue YB, Wang XL, Zheng YM, Zhang JS, Liu RH. Inhibitory effects of c9, t11-conjugated linoleic acid on invasion of human gastric carcinoma cell line SGC-7901. World J Gastroenterol 2003; 9:1909-1914. [PMID: 12970874 PMCID: PMC4656642 DOI: 10.3748/wjg.v9.i9.1909] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2003] [Revised: 04/23/2003] [Accepted: 05/11/2003] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effect of c9, t11-conjugated linoleic acid (c9, t11-CLA) on the invasion of human gastric carcinoma cell line and its possible mechanism of preventing metastasis. METHODS Using reconstituted basement membrane invasion, chemotaxis, adhesion, PAGE substrate zymography and RT-PCR assays, we analyzed the abilities of invasion, direct migration, adhesion of intracellular matrix, as well as the activity of type IV collagenase and expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 mRNA in SGC-7901 cells which were treated with gradually increased concentrations (25, 50, 100 and 200 micromol/L) of c9, t11-CLA for 24 h. RESULTS At the concentrations of 200 micromol/L, 100 micromol/L and 50 micromol/L, c9,t11-CLA suppressed the invasion of SGC-7901 cells into the reconstituted basement membrane by 53.7 %, 40.9 % and 29.3 %, respectively, in comparison with the negative control. Only in the 200 micromol/L c9,t11-CLA group, the chemotaxis of SGC-7901 cells was inhibited by 16.0 % in comparison with the negative control. C9,t11-CLA also could inhibit the adhesion of SGC-7901 cells to laminin, fibronectin and Matrigel, increase the expression of TIMP-1 and TIMP-2 mRNA, and reduce type IV collagenase activities in the serum-free medium supernatant of SGC-7901 cells. CONCLUSION c9,t11-CLA can inhibit the invasion of SGC-7901 cells at multiple procedures in tumor metastasis cascade, which may be associated with the induction of TIMP-1 and TIMP-2 mRNA expression.
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Affiliation(s)
- Bing-Qing Chen
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 199 Dongdazhi Street, Nangang District, Harbin 150001, Heilongjiang Province, China.
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Secchiari P, Antongiovanni M, Mele M, Serra A, Buccioni A, Ferruzzi G, Paoletti F, Petacchi F. Effect of kind of dietary fat on the quality of milk fat from Italian Friesian cows. ACTA ACUST UNITED AC 2003. [DOI: 10.1016/s0301-6226(03)00043-5] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Rajakangas J, Basu S, Salminen I, Mutanen M. Adenoma growth stimulation by the trans-10, cis-12 isomer of conjugated linoleic acid (CLA) is associated with changes in mucosal NF-kappaB and cyclin D1 protein levels in the Min mouse. J Nutr 2003; 133:1943-8. [PMID: 12771343 DOI: 10.1093/jn/133.6.1943] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Conjugated linoleic acid (CLA) is a term used to describe the different conjugated isomers of linoleic acid. CLA has been found to be anticarcinogenic in mammary cancer, but its effects on colon carcinogenesis are still inconclusive. In this study, the isomer-specific effects of the cis-9, trans-11 and trans-10, cis-12 CLA isomers were investigated in the Min mouse model for intestinal carcinogenesis. The Min mice (n = 10/group) were fed either an AIN-93G control diet or a diet containing 1 g/100 g cis-9, trans-11 or trans-10, cis-12 CLA for 8 wk. The number and size of adenomas were measured and the proteins from the small intestinal tissues extracted for immunoblotting analysis. The number of adenomas did not differ, but the size of the adenomas was greater in the distal part of the small intestine in mice fed the trans-10, cis-12 isomer than in controls (1.19 +/- 0.16 vs. 0.94 +/- 0.21 mm, mean +/- SD, P < 0.01). The same isomer caused an increase in lipid peroxidation, measured as urinary 8-iso-prostaglandin (PG)F(2alpha). Nuclear p65 protein of the mucosal tissue was not detectable in the trans-10, cis-12 group, which differed (P < 0.05) from the control group. Cyclin D1, a target for the nuclear factor (NF)-kappaB pathway, was elevated in the trans-10, cis-12 group compared with the control group (P < 0.01), but cyclooxygenase-2 levels were not higher. There was no difference in beta-catenin protein levels between the groups. The results indicate that the trans-10, cis-12 isomer of CLA can act as a cancer promoter in colon carcinogenesis possibly through pathways affecting NF-kappaB and cyclin D1.
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Affiliation(s)
- Johanna Rajakangas
- Department of Applied Chemistry and Microbiology, Division of Nutrition, University of Helsinki, Helsinki, Finland.
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Albers R, van der Wielen RPJ, Brink EJ, Hendriks HFJ, Dorovska-Taran VN, Mohede ICM. Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men. Eur J Clin Nutr 2003; 57:595-603. [PMID: 12700622 DOI: 10.1038/sj.ejcn.1601585] [Citation(s) in RCA: 143] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2002] [Revised: 06/10/2002] [Accepted: 06/26/2002] [Indexed: 11/08/2022]
Abstract
OBJECTIVES To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. DESIGN Double-blind, randomized, parallel, reference-controlled intervention study. SUBJECTS AND INTERVENTION Seventy-one healthy males aged 31-69 y received one of the following treatments: (1). mixture of 50% c9,t11 CLA and 50% t10,c12 CLA isomers (CLA 50:50); (2). mixture of 80% c9,t11 CLA and 20% t10,c12 CLA isomers (CLA 80:20); and (3). sunflower oil fatty acids (reference). The treatments were given as supplements in softgel capsules providing a total of 1.7 g (c9,t11+t10,c12) CLA fatty acids (50:50) or 1.6 g (c9,t11+t10,c12) CLA glycerides (80:20) per day in treatment groups for 12 weeks. RESULTS Almost twice as many subjects reached protective antibody levels to hepatitis B when consuming CLA 50:50 fatty acids (15/24, 62%) compared with subjects consuming the reference substance (7/21, 33%, P=0.075). In subjects consuming CLA 80:20 glycerides this was 8/22 (36%). Other aspects of immune function, ie DTH responses, NK cell activity, lymphocyte proliferation and production of TNF-alpha, IL1-beta, IL6, IFN-gamma, IL2, IL4, and PGE(2), were not affected. CONCLUSION This is the first study that suggests that CLA may beneficially affect the initiation of a specific response to a hepatitis B vaccination. This was seen in the CLA 50:50, but not in the CLA 80:20 group.
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Affiliation(s)
- R Albers
- Unilever Health Institute, Unilever Research Vlaardingen, Vlaardingen, The Netherlands.
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Kelley DS, Erickson KL. Modulation of body composition and immune cell functions by conjugated linoleic acid in humans and animal models: benefits vs. risks. Lipids 2003; 38:377-86. [PMID: 12848282 DOI: 10.1007/s11745-003-1072-2] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
We have reviewed the published literature regarding the effects of CLA on body composition and immune cell functions in humans and in animal models. Results from studies in mice, hamsters, rats, and pigs generally support the notion that CLA reduced depot fat in the normal or lean strains. However, in obese rats, it increased body fat or decreased it less than in the corresponding lean controls. These studies also indicate that t10,c12-CLA was the isomer that reduced adipose fat; however, it also increased the fat content of several other tissues and increased circulating insulin and the saturated FA content of adipose tissue and muscle. Four of the eight published human studies found small but significant reductions in body fat with CLA supplementation; however, the reductions were smaller than the prediction errors for the methods used. The other four human studies found no change in body fat with CLA supplementation. These studies also report that CLA supplementation increased the risk factors for diabetes and cardiovascular disease including increased blood glucose, insulin, insulin resistance, VLDL, C-reactive protein, lipid peroxidation, and decreased HDL. Most studies regarding the effects of CLA on immune cell functions have been conducted with a mixture of isomers, and the results have been variable. One study conducted in mice with the purified c9,t11-CLA and t10,c12-CLA isomers indicated that the two isomers have similar effects on immune cell functions. Some of the reasons for the discrepancies between the effects of CLA in published reports are discussed. Although significant benefit to humans from CLA supplementation is questionable, it may create several health risks in both humans and animals. On the basis of the published data, CLA supplementation of adult human diets to improve body composition or enhance immune functions cannot be recommended at this time.
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Affiliation(s)
- D S Kelley
- Western Human Nutrition Research Center, ARS, USDA, Department of Nutrition, University of California Davis, Davis, California 95616, USA.
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Abstract
The human diet contains numerous endocrine-active compounds that influence mammalian physiology. The effects of these dietary compounds may be mediated by interaction with well-characterized intracellular hormone receptors or by other effects on patterns of endogenous hormone production, metabolism, target tissue signaling, growth, or differentiation. Because humans evolved as omnivores, the spectrum of dietary compounds that can be tolerated at modest levels of intake without frank toxicity is broad. Modest intake of these diverse nonnutritive endocrine-active compounds offers potential human health benefits through modulation of metabolic and hormonal responses, especially in sedentary individuals consuming a highly refined diet.
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Affiliation(s)
- Claude L Hughes
- Department of Medical and Scientific Services, Quintiles, Inc, Research Triangle Park, NC 27709-3979, USA.
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Ip MM, Masso-Welch PA, Ip C. Prevention of mammary cancer with conjugated linoleic acid: role of the stroma and the epithelium. J Mammary Gland Biol Neoplasia 2003; 8:103-18. [PMID: 14587866 DOI: 10.1023/a:1025739506536] [Citation(s) in RCA: 77] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Conjugated linoleic acid (CLA), found naturally in dairy products and ruminant meats, refers to isomers of octadecadienoic acid with conjugated double bonds. CLA inhibits both DMBA- and NMU-induced rat mammary carcinogenesis, and its antitumor efficacy is similar whether it is fed only during puberty, or continuously during promotion. Pubertal feeding is associated with a reduced proliferation of the epithelial cells within the terminal end buds (TEBs) and lobular epithelium, and results in a decrease in the epithelial density, suggesting a reduction in the carcinogen-sensitive target population. During promotion, CLA feeding induces apoptosis of preneoplastic lesions. The effects of CLA are mediated by a direct action on the epithelium, as well as by an indirect effect through the stroma. CLA is incorporated into the neutral lipids of mammary adipocytes, where it can serve as a local reservoir of CLA. Additionally, CLA induces the adipogenic differentiation of multipotent mammary stromal cells in vitro, and inhibits their development into three-dimensional capillary networks. This suggested that CLA might inhibit angiogenesis in vivo, a hypothesis that was subsequently confirmed. The antiangiogenic effect is mediated, in part, through a CLA-induced decrease in serum VEGF (vascular endothelial growth factor) and mammary gland VEGF and flk-1. Together, the data suggest that CLA may be an excellent candidate for prevention of breast cancer.
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Affiliation(s)
- Margot M Ip
- Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
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Chen BQ, Xue YB, Liu JR, Yang YM, Zheng YM, Wang XL, Liu RH. Inhibition of conjugated linoleic acid on mouse forestomach neoplasia induced by benzo (a) pyrene and chemopreventive mechanisms. World J Gastroenterol 2003; 9:44-49. [PMID: 12508349 PMCID: PMC4728246 DOI: 10.3748/wjg.v9.i1.44] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2002] [Revised: 10/01/2002] [Accepted: 10/12/2002] [Indexed: 02/06/2023] Open
Abstract
AIM To explore the inhibition of conjugated linoleic acid isomers in different purity (75 % purity c9,t11-, 98 % purity c9,t11- and 98 % purity t10,c12-CLA) on the formation of forestomach neoplasm and chemopreventive mechanisms. METHODS Forestomach neoplasm model induced by B(a)P in KunMing mice was established. The numbers of tumor and diameter of each tumor in forestomach were counted; the mice plasma malondialdehyde (MDA) were measured by TBARS assay; TUNEL assay was used to analyze the apoptosis in forestomach neoplasia and the expression of MEK-1, ERK-1, MKP-1 protein in forestomach neoplasm were studied by Western Blotting assay. RESULTS The incidence of neoplasm in B(a)P group, 75 % purity c9, t11-CLA group, 98 % purity c9,t11-CLA group and 98 % purity t10, c12-CLA group was 100 %, 75.0 %(P>0.05), 69.2 % (P<0.05) and 53.8 % (P<0.05) respectively and the effect of two CLA isomers in 98 % purity on forestomach neoplasia was significant; CLA showed no influence on the average tumor numbers in tumor-bearing mouse, but significantly decreased the tumor size, the tumor average diameter of mice in 75 % purity c9,t11-CLA group, 98 % purity c9,t11-CLA group and 98 % purity t10, c12-CLA group was 0.157+/-0.047 cm, 0.127+/-0.038 cm and 0.128+/-0.077 cm (P<0.05) and 0.216+/-0.088 cm in B(a)P group; CLA could also significantly increase the apoptosis cell numbers by 144.00+/-20.31, 153.75+/-23.25, 157.25+/-15.95(P<0.05) in 75 % purity c9,t11-CLA group, 98 % purity c9,t11-CLA group and 98 % purity t10,c12-CLA group (30.88+/-3.72 in BP group); but there were no significant differences between the effects of 75 % purity c9,t11-CLA and two isomers in 98 % purity on tumor size and apoptotic cell numbers; the plasma levels of MDA in were increased by 75 % purity c9,t11-CLA, 98 % purity c9,t11-CLA and 98 % purity t10,c12-CLA. The 75 % purity c9,t11-CLA showed stronger inhibition; CLA could also inhibit the expression of ERK-1 protein and promote the expression of MKP-1 protein, however no influence of CLA on MEK-1 protein was observed. CONCLUSION Two isomers in 98 % purity show stronger inhibition on carcinogenesis. However, the inhibitory mechanisms of CLA on carcinogenesis is complicated, which may be due to the increased mice plasma MDA, the inducing apoptosis in tumor tissues. And the effect of CLA on the expression of ERK-1 and MKP-1 may be one of the mechanisms of the inhibition of CLA on the tumor.
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Affiliation(s)
- Bing-Qing Chen
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
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KAWAHARA S, TAKENOYAMA SI, NAGATO C, MUGURUMA M, ITO T, YAMAUCHI K. Evaluation of beef tallow as a natural source of conjugated linoleic acid. Anim Sci J 2002. [DOI: 10.1046/j.1344-3941.2002.00073.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Abstract
Conjugated linoleic acid (CLA) is a group of polyunsaturated fatty acids found in beef, lamb, and dairy products that exist as positional and stereo-isomers of octadecadienoate (18:2). Over the past two decades numerous health benefits have been attributed to CLA in experimental animal models including actions to reduce carcinogenesis, atherosclerosis, onset of diabetes, and body fat mass. The accumulation of CLA isomers and several elongated/desaturated and beta-oxidation metabolites have been found in tissues of animals fed diets with CLA. Molecular mechanisms of action appear to include modulation of eicosanoid formation as well as regulation of the expression of genes coding for enzymes known to modulate macronutrient metabolism. This review focuses on health benefits, metabolism, and potential mechanisms of action of CLA and postulates the implications regarding dietary CLA for human health.
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Affiliation(s)
- Martha A Belury
- Department of Molecular Medicine, Northwest Hospital, 21720 23rd Drive SE, Bothell, Washington 98021, USA.
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Liu JR, Chen BQ, Yang YM, Han XH, Xue YB, Wang XL, Zheng YM, Liu RH. Effects ofcis-9,trans-11-conjugated linoleic acid on cancer cell cycle. Environ Health Prev Med 2002; 7:205-210. [PMID: 21432279 PMCID: PMC2723588 DOI: 10.1007/bf02898006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2001] [Accepted: 07/22/2002] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVES To determine the effect of cis-9, trans-11-conjugated linoleic acid on the cell cycle of mammary cancer cells (MCF-7) and its possible mechanism of inhibition cancer growth. METHODS Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B(1), D(1), p16(ink4a) and p21(cip/wafl) of MCF-7 cells which were treated with various c9, t11-CLA concentrations (25 mM, 50 mM, 100 mM and 200 mM) of c9, t11-CLA for 24 and 48 h, with negative controls (0.1% ethanol). RESULTS The cell growth and DNA synthesis of MCF-7 cells were inhibited by c9, t11-CLA. MCF-7 cells, after treatment with various c9, t11-CLA doses mentioned above for 8 days, the inhibition frequency was 27.18%, 35.43%, 91.05%, and 92.86%, respectively and the inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 mM, 24 h) incorporated significantly less(3)H-TdR than did the negative control (P<0.05 andP<0.01). To further investigate the influence on the cell cycle progression, we found that c9, t11-CLA may arrest the cell cycle of MCF-7 cells. Immunocytochemical staining demonstrated that MCF-7 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA, and Cyclin, A, B(1), D(1) compared with the negative controls (P<0.01), whereas the expressions of p16(ink4a) and p21(cip/wafl), cyclin-dependent kinases inhibitors (CDKI), were increased. CONCLUSIONS The cell growth and proliferation of MCF-7 cells is inhibited by c9, t11-CLA by blocking the cell cycle, which reduces expressions of cyclin A, B(1), D(1) and enhances expressions of CDKI (p16(ink4a) and p21(cip/wafl)).
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Affiliation(s)
- Jia Ren Liu
- Public Health College of Harbin Medical University, 199 Dongdazhi Street, Nangang District, Harbin, Heilongijang, P.R. China,
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Yamasaki M, Ikeda A, Hirao A, Tanaka Y, Miyazaki Y, Rikimaru T, Shimada M, Sugimachi K, Tachibana H, Yamada K. Effect of dietary conjugated linoleic acid on the in vivo growth of rat hepatoma dRLh-84. Nutr Cancer 2002; 40:140-8. [PMID: 11962249 DOI: 10.1207/s15327914nc402_10] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
We examined the effect of dietary conjugated linoleic acid (CLA) on the growth of injected hepatoma dRLh-84 in Donryu rats. After experimental diets containing 0% or 2% CLA were given to male Donryu rats for 3 wk, dRLh-84 cells were injected into the left lobe of the hepatic capsule, and the experimental diet was continued. The cells formed a solid tumor > or = 1 wk after the injection, and thereafter the tumor grew with feeding duration. In a morphological study, this tumor appeared to be a low-differentiated hepatoma, and there was no remarkable difference in the morphology of the tumor between 0% and 2% CLA groups. Tumor weight was significantly higher in the 2% CLA group than in the 0% CLA group throughout the feeding period after the injection. Serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase activities were significantly higher in 2% CLA-injected rats than in 0% CLA-injected rats at 3 wk after the injection. CLA upregulated acyl-CoA oxidase activity, especially 1 wk after the injection. However, dietary CLA did not activate carnitine palmitoyl transferase II, which is a rate-limiting enzyme in the mitochondrial beta-oxidation pathway. Natural killer cell activity in the spleen tended to be higher in injected rats, but a significant effect of dietary CLA was not recognized. Serum interferon-gamma and tumor necrosis factor-alpha levels were higher in injected than in sham rats. Moreover, these levels were higher in 2% CLA groups than in the respective 0% CLA groups.
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Affiliation(s)
- M Yamasaki
- Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan
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Voorrips LE, Brants HAM, Kardinaal AFM, Hiddink GJ, van den Brandt PA, Goldbohm RA. Intake of conjugated linoleic acid, fat, and other fatty acids in relation to postmenopausal breast cancer: the Netherlands Cohort Study on Diet and Cancer. Am J Clin Nutr 2002; 76:873-82. [PMID: 12324303 DOI: 10.1093/ajcn/76.4.873] [Citation(s) in RCA: 152] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Conjugated linoleic acid (CLA), which is present in milk products and meat from ruminants, appears to have anticarcinogenic activity against breast cancer in animal and in vitro experiments. To date, few epidemiologic data are available in humans. OBJECTIVE This study evaluated the relation between intakes of CLA and other fatty acids and breast cancer incidence in the Netherlands Cohort Study. DESIGN Intake data derived from a validated 150-item food-frequency questionnaire were linked to an existing database with analytic data on specific fatty acids in European foods (the TRANSFAIR study). With 6.3 y of follow-up and 941 incident cases of breast cancer, multivariate rate ratios and 95% CIs were calculated for energy-adjusted intakes of fatty acids and CLA-containing food groups (eg, butter, cheese, milk, other milk products, and meat). RESULTS CLA intake showed a weak, positive relation with breast cancer incidence (rate ratio for highest compared with lowest quintile: 1.24, 95% CI: 0.91, 1.69; P for trend = 0.02). Statistically significant positive associations were found with total trans fatty acids and (borderline) with saturated fatty acids. Significant inverse associations were found with monounsaturated and cis unsaturated fatty acids, whereas total fat and energy intake of CLA-containing food groups were not related to breast cancer incidence. CONCLUSION The suggested anticarcinogenic property of CLA in animal and tissue culture models could not be confirmed in this epidemiologic study in humans.
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Affiliation(s)
- Laura E Voorrips
- Department of Nutritional Epidemiology, TNO Nutrition and Food Research, Zeist, Netherlands.
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Belury MA. Inhibition of carcinogenesis by conjugated linoleic acid: potential mechanisms of action. J Nutr 2002; 132:2995-8. [PMID: 12368384 DOI: 10.1093/jn/131.10.2995] [Citation(s) in RCA: 188] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Conjugated linoleic acid (CLA) is composed of positional and stereoisomers of octadecadienoate (18:2); it is found in foods derived from ruminants (beef and lamb as well as dairy products from these sources). When a mixture of isomers is fed to experimental animals, chemically induced tumorigenesis of mammary, skin and colon is reduced. Importantly, many isomers of CLA are readily metabolized to desaturated/elongated products as well as beta-oxidized products, suggesting that these metabolites may be important anticancer compounds. Mechanisms of inhibition of carcinogenesis may include reduction of cell proliferation, alterations in the components of the cell cycle and induction of apoptosis. In addition, CLA modulates markers of immunity and eicosanoid formation in numerous species as well as lipid metabolism and gene expression. It is likely that CLA exerts inhibitory properties in carcinogenesis via one or more of these pathways with some tissue specificity. This review will explore recent advances in putative mechanisms of reduction of carcinogenesis by CLA.
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Affiliation(s)
- Martha A Belury
- Department of Molecular Medicine, Northwest Hospital, Bothell, WA 98021, USA.
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Miller A, Stanton C, Devery R. Modulation of arachidonic acid distribution by conjugated linoleic acid isomers and linoleic acid in MCF-7 and SW480 cancer cells. Lipids 2001; 36:1161-8. [PMID: 11768161 DOI: 10.1007/s11745-001-0827-0] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
The relationship between growth and alterations in arachidonic acid (AA) metabolism in human breast (MCF-7) and colon (SW480) cancer cells was studied. Four different fatty acid preparations were evaluated: a mixture of conjugated linoleic acid (CLA) isomers (c9,t11, t10,c12, c11,t13, and minor amounts of other isomers), the pure c9,t11-CLA isomer, the pure t10,c12-CLA isomer, and linoleic acid (LA) (all at a lipid concentration of 16 microg/mL). 14C-AA uptake into the monoglyceride fraction of MCF-7 cells was significantly increased following 24 h incubation with the CLA mixture (P < 0.05) and c9,t11-CLA (P < 0.02). In contrast to the MCF-7 cells, 14C-AA uptake into the triglyceride fraction of the SW480 cells was increased while uptake into the phospholipids was reduced following treatment with the CLA mixture (P < 0.02) and c9,t11-CLA (P < 0.05). Distribution of 14C-AA among phospholipid classes was altered by CLA treatments in both cell lines. The c9,t11-CLA isomer decreased (P < 0.05) uptake of 14C-AA into phosphatidylcholine while increasing (P < 0.05) uptake into phosphatidylethanolamine in both cell lines. Both the CLA mixture and the t10,c12-CLA isomer increased (P < 0.01) uptake of 14C-AA into phosphatidylserine in the SW480 cells but had no effect on this phospholipid in the MCF-7 cells. Release of 14C-AA derivatives was not altered by CLA treatments but was increased (P < 0.05) by LA in the SW480 cell line. The CLA mixture of isomers and c9,t11-CLA isomer inhibited 14C-AA conversion to 14C-prostaglandin E2 (PGE2) by 20-30% (P < 0.05) while increasing 14C-PGF2alpha by 17-44% relative to controls in both cell lines. LA significantly (P < 0.05) increased 14C-PGD2 by 13-19% in both cell lines and increased 14C-PGE2 by 20% in the SW480 cell line only. LA significantly (P < 0.05) increased 5-hydroperoxyeicosatetraenoate by 27% in the MCF-7 cell line. Lipid peroxidation, as determined by increased levels of 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), was observed following treatment with c9,t11-CLA isomer in both cell lines (P < 0.02) and with t10,c12-CLA isomer in the MCF-7 cell line only (P < 0.05). These data indicate that the growth-promoting effects of LA in the SW480 cell line may be associated with enhanced conversion of AA to PGE2 but that the growth-suppressing effects of CLA isomers in both cell lines may be due to changes in AA distribution among cellular lipids and an altered prostaglandin profile.
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Affiliation(s)
- A Miller
- School of Biotechnology, Dublin City University, Dublin, Ireland
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Kimoto N, Hirose M, Futakuchi M, Iwata T, Kasai M, Shirai T. Site-dependent modulating effects of conjugated fatty acids from safflower oil in a rat two-stage carcinogenesis model in female Sprague–Dawley rats. Cancer Lett 2001; 168:15-21. [PMID: 11368872 DOI: 10.1016/s0304-3835(01)00459-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Modifying effects of dietary administration of conjugated fatty acids from safflower oil (CFA-S), rich in conjugated linoleic acid, on major organs were examined in the post-initiation stage of a two-stage carcinogenesis model in female rats. Groups of 21 or 22 F344 female rats were treated sequentially with 2,2'-dihydroxy-di-n-propylnitosamine (intragastrically, i.g.), 7,12-dimethylbenz[a]anthracene (i.g.), 1,2-dimethylhydrazine (subcutaneously) and N-butyl-N-(4-hydroxybutyl)nitrosamine (in drinking water) during the first 3 weeks for initiation, and then administered diet containing 1 or 0.1% CFA-S for 33 weeks. Further groups of animals were treated with carcinogens or 1% CFA-S alone, or maintained as non-treated controls. All surviving animals were killed at week 36, and major organs were examined histopathologically for development of pre-neoplastic and neoplastic lesions. The 1 and 0.1% CFA-S treatment significantly decreased the incidence and multiplicity of mammary carcinomas, though a clear dose response was not observed. In the urinary bladder, the incidence of papillary or nodular hyperplasia but not tumors was significantly increased in the 1% CFA-S-treated group. The results indicate that low dose CFA-S may find application as a potent chemopreventor of mammary carcinogenesis.
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Affiliation(s)
- N Kimoto
- First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, 467-8601, Nagoya, Japan
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Bulgarella JA, Patton D, Bull AW. Modulation of prostaglandin H synthase activity by conjugated linoleic acid (CLA) and specific CLA isomers. Lipids 2001; 36:407-12. [PMID: 11383694 DOI: 10.1007/s11745-001-0736-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Conjugated linoleic acid (CLA) has been shown to inhibit tumorigenesis in animal models and is cytostatic to numerous cell lines in vitro. However, the mechanism of action is unknown. In the current study, we determined the effects of CLA and specific isomers of CLA on the rate of oxygenation of arachidonic acid by prostaglandin H synthase (PGHS) in ram seminal vesicle microsomes. The enzyme was incubated with 0.1 to 100 microM CLA or specific isomers of CLA for 2 min prior to the addition of 44 to 176 microM arachidonate. The isomers tested were 9(E),11(E) CLA; 9(Z),11(E) CLA; 9(Z),11(Z) CLA, and 10(E),12(2) CLA. For a positive inhibitor control, flurbiprofen was used at 0.75 to 2.50 microM. Enzyme activity was assessed by measuring the rate of oxygen consumption. Inclusion of CLA or specific isomers of CLA in the incubation mixtures inhibits PGHS. The efficacy differs for each isomer, with the 9(Z),11 (E) CLA isomer being the most effective and the 9(Z),11 (Z) CLA isomer being the least effective inhibitor among the four CLA isomers tested. The Ki values obtained by Dixon replots range from 18.7 microM for the most effective isomer, 9(Z),11 (E) CLA, to 105.3 microM for the least effective isomer, 9(2),11(2) CLA. The Ki value for flurbiprofen with ram seminal vesicle microsomes was 0.33 microM. As the concentration of arachidonate was increased, the CLA-dependent inhibition of PGHS decreased, suggesting competitive inhibition. The results of this study demonstrate the potential of CLA and specific isomers of CLA to modulate prostaglandin biosynthesis.
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Affiliation(s)
- J A Bulgarella
- Department of Chemistry, Oakland University, Rochester, Michigan 48309-4477, USA
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McCarty MF. The chlorophyll metabolite phytanic acid is a natural rexinoid--potential for treatment and prevention of diabetes. Med Hypotheses 2001; 56:217-9. [PMID: 11425290 DOI: 10.1054/mehy.2000.1153] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Synthetic ligands of the retinoid X receptor (RXR) have shown antidiabetic activity in mice, apparently owing to the fact that they stimulate the transcriptional activity of PPAR-gamma/RXR heterodimers, much like thiazolidinedione drugs. The chlorophyll metabolite phytanic acid has been shown to be a natural ligand for RXR, active in concentrations near its physiological levels. It is thus reasonable to suspect that phytanic acid may have utility for treatment and prevention of human type 2 diabetes. Phytanic acid may mimic or complement various effects of conjugated linoleic acids, which have been shown to activate PPAR-gamma/RXR and prevent rodent diabetes. Administration of hydrolyzed chlorophyll may represent the most cost-effective strategy for raising human tissue levels of phytanic acid.
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Affiliation(s)
- M F McCarty
- Pantox Laboratories, 4622 Santa Fe Street, San Diego, CA 92109, USA
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