Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-28T03:59:40.743Z Has data issue: false hasContentIssue false
  • English
  • Français

Conjugated linoleic acid: a novel therapeutic nutrient?

Published online by Cambridge University Press:  14 December 2007

Helen M Roche ,
Enda Noone  and
Anne Nugent Michael J Gibney
Helen M Roche*
Affiliation:
Unit of Nutrition Dept of Clinical MedicineTrinity Health Sciences Centre, St James's HospitalDublin 8, Ireland
Enda Noone
Affiliation:
Unit of Nutrition Dept of Clinical MedicineTrinity Health Sciences Centre, St James's HospitalDublin 8, Ireland
Anne Nugent Michael J Gibney
Affiliation:
Unit of Nutrition Dept of Clinical MedicineTrinity Health Sciences Centre, St James's HospitalDublin 8, Ireland
*
*Corresponding author: Dr Helen M. Roche, fax +353 1 4542043, email hmroche@tcd.ie
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Conjugated linoleic acid (CLA) refers to a group of fatty acid isomers of linoleic acid. Recent research shows that CLA affects body composition, lipoprotein metabolism, inflammationand carcinogenesis. Therefore, CLA may have potential as a therapeutic nutrient with respect to many common diseases, including obesity, atherosclerosis, chronic inflammatory diseases and cancer. Animal studies show that CLA is a potent anti-adipogenic nutrient, reducing adipose tissue mass and increasing lean mass. However, the effect of CLA on body composition in human subjects has been less spectacular. Several studies have demonstrated that CLA significantly improves plasma cholesterol and triacylglycerol metabolism in a number of animal models. These studies also showed that CLA inhibits the progression and pathogenesis of atherosclerosis. Whilst CLA has also been shown toimprove triacylglycerol metabolism in human subjects, it has not been determined whether CLA affects atherogenesis. Animal models show that CLA-rich diets modulate the inflammatory response and preliminary trials with human subjects show that CLA affects the cell-mediated immune response. The molecular basis of the health effects of CLA has not been elucidated, but it is probable that CLA mediates its effect in a number of ways including altered eicosanoid or cytokine metabolism and/orby a direct effect of dietary fats on gene transcription. Most of our knowledge is based on in vitro and animal studies; the challenge is to define the nature and molecular basis of any health effects of CLA in human subjects.

Keywords

Conjugated linoleic acidCoronary heart diseaseLipid metabolism
Type
Research Article
Information
Nutrition Research Reviews , Volume 14 , Issue 1 , June 2001 , pp. 173 - 188
Copyright
Copyright © CABI Publishing 2001

References

Adlof, RO, Duval, S & Emken, EA (2000) Biosynthesis of conjugated linoleic acid in humans. Lipids 35, 131–135.CrossRefGoogle ScholarPubMed
Azain, MJ, Hausman, DB, Sisk, MB, Flatt, WP & Jewell, DE (2000) Dietary conjugated linoleic acid reduces rat adipose tissue cell size rather than cell number. Journal of Nutrition 130, 1548–1554.CrossRefGoogle ScholarPubMed
Basu, S, Smedman, A & Vessby, B (2000) Conjugated linoleic acid induces lipid peroxidation in humans. FEBS Letters 468, 33–36.CrossRefGoogle ScholarPubMed
Belury, MA, Moya-Camarena, SY, Liu, KL & Vanden Heuvel, JP (1997) Dietary conjugated linoleic acid induces peroxisone-specific enzyme accumulation and ornithine decarboxylase activity in mouse liver. Nutritional Biochemistry 8, 579–584.CrossRefGoogle Scholar
Brodie, AE, Manning, VA, Ferguson, KR, Jewell, DE & Hu, CY (1999) Conjugated linoleic acid inhibits differentiation of pre– and post–confluent 3T3-L1 preadipocytes but inhibits cell proliferation only in preconfluent cells. Journal of Nutrition 129, 602–606.CrossRefGoogle ScholarPubMed
Brown, DW & Moore, WEC (1960) Distribution of Butyrivibrio fibrisolvens in nature. Journal of Dairy Science 43, 1570–1574.CrossRefGoogle Scholar
Cahlin, C, Korner, A, Axelsson, H, Wang, W, Lundholm, K & Svanberg, E (2000) Experimental cancer cachexia: the role of host-derived cytokines interleukin (IL)–6, IL–12, interferon-gamma, and tumor necrosis factor alpha evaluated in gene knockout, tumor–bearing mice on C57 Bl background and eicosanoid–dependent cachexia. Cancer Research 60, 5488–5493.Google ScholarPubMed
Chew, BP, Wong, TS, Shultz, TD & Magnuson, NS (1997) Effect of conjugated dieonic derivatives of linoleic acid and β-carotene in modulating lymphocyte and macrophage function. Anticancer Research 17, 1099–1106.Google Scholar
Chin, SF, Lui, W, Strokson, JM, Ha, YL & Pariza, MW (1992) Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognised class of anti-carcinogenesis. Journal of Food Composition and Analysis 5, 266–277.CrossRefGoogle Scholar
Choi, Y, Kim, YC, Han, YB, Park, Y, Pariza, MW & Ntambi, JM (2000) The trans-10, cis-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3–L1 adipocytes. Journal of Nutrition 130, 1920–1924.CrossRefGoogle ScholarPubMed
De Deckere, EAM, van Amelsvoort, JMM, Rudrum, M & Lin, Y (1999) Effects of different conjugated linoleic acid isomers on lipid variables in hamsters. FASEB Journal 13, LB207.Google Scholar
DeLany, JP, Bolhm, F, Truett, AA, Scimeca, JA & West, DB (1999) Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake. American Journal of Physiology 276, R1172–R1179.Google ScholarPubMed
Fruchard, J-C, Duriez, P & Staels, B (1999) Peroxisome proliferator-activated receptor–alpha receptors regulate genes governing lipoprotein|metabolism, vascular inflammation and atherosclerosis. Current Opinion in Lipidology 10, 245–257.CrossRefGoogle Scholar
Gavino, VC, Gavino, G, Leblanc, M-J & Tuchweber, B (2000) An isomeric mixture of conjugated linoleic acids but not pure cis-9, trans-11-octadecadienoic acid affects body weight gain and plasma lipids in hamsters. Journal of Nutrition 130, 27–29.CrossRefGoogle Scholar
Griinari, JM, Dwyer, DA, McGuire, MA, Bauman, DE, Palmquist, DL & Nurmela, KVV (1998) Trans-octadecenoic acids and mild fat depression in lactating dairy cows. Journal of Dairy Science 81, 1251–1261.CrossRefGoogle Scholar
Hayek, MG, Han, SN, Wu, D, Watkins, BA, Meydani, M, Dorsey, JL, Smith, DE & Meydani, SN (1999) Dietary conjugated linoleic acid influences the immune response of young and old C57BL/6NCrlBR Mice. Journal of Nutrition 129, 32–38.CrossRefGoogle Scholar
Herbel, BK, McGuire, MK, McGuire, MA & Shultz, TD (1998) Safflower oil consumption does not increase plasma conjugated linoleic acid concentrations in humans. American Journal of Clinicial Nutrition 67, 332–337.CrossRefGoogle Scholar
Hotamisligil, GS (1999) The role of TNFalpha and TNF receptors in obesity and insulin resistance. Journal of International Medicine 245, 621–625.CrossRefGoogle ScholarPubMed
Houseknecht, KL, Vanden Heuvel, JP, Moya-Camarena, SY, Portocarrero, CP, Peck, LW, Nickel, KP & Belury, MA (1998) Dietary conjugated linoleic acid normalises impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat. Biochemical and Biophysical Research Communications 244, 678–682.CrossRefGoogle ScholarPubMed
Huang, YC, Luedecke, LO & Shultz, TD (1994) Effect of cheddar cheese consumption on the plasma conjugated linoleic acid concentration in men. Nutrition Research 14, 373–386.CrossRefGoogle Scholar
Jiang, J, Ting, AT & Seed, B (1998) PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature 391, 82–86.CrossRefGoogle ScholarPubMed
Jiang, J, Wolk, A & Vessby, B (1999) Relation between the intake of milk fat and the occurrence of conjugated linoleic acid in human adipose tissue. American Journal of Clinical Nutrition 70, 21–27.CrossRefGoogle ScholarPubMed
Kepler, CR, Hirons, KP, McNeill, JJ & Tove, SB (1966) Intermediates and products of the biohydrogenation of linoleic acid by Butyrivibrio fibrisolvens. Journal of Biological Chemistry 241, 1350–1354.CrossRefGoogle Scholar
Kersten, S, Desvergne, B & Wahli, W (2000) Roles of PPARs in health and disease. Nature 405, 421–424.CrossRefGoogle ScholarPubMed
Klingenberg, M & Huang, SG (1999) Structure and function of the uncoupling proteins from brown adipose tissue. Biochimica et Biophysica Acta 1415, 271–296.CrossRefGoogle ScholarPubMed
Kritchevsky, D (2000) Antimutagenic and some other effects of conjugated linoleic acid. British Journal of Nutrition 83, 459–465.CrossRefGoogle ScholarPubMed
Kritchevsky, D, Tepper, SA, Wright, S, Tso, P & Czarnecki, SK (2000) Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits. Journal of the American College of Nutrition 19, 742S–477S.CrossRefGoogle ScholarPubMed
Lee, KN, Kritchevsky, D & Pariza, MW (1994) Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis 108, 19–25.CrossRefGoogle ScholarPubMed
Lee, KN, Pariza, MW & Ntambi, JM (2000) Conjugated linoleic acid decreases hepatic stearoyl–CoA desaturase mRNA expression. Biochemical and Biophysical Research Communications 248, 817–821.CrossRefGoogle Scholar
Li, AC, Brown, KK, Silvestre, MJ, Willson, TM, Palinske, W & Glass, CK (2000) Peroxisome proliferator-activated receptor γ ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. Journal of Clinical Investigation 106, 523–531.CrossRefGoogle ScholarPubMed
Lin, H, Boylston, TD, Chang, MJ, Luedecke, LO & Schultz, TD (1995) Survey of the conjugated linoleic acid contents of dairy products. Journal of Dairy Science 78, 2358–2365.CrossRefGoogle ScholarPubMed
Lowell, BB (1999) PARgamma: an essential regulator of adipogenesis and modulator of fat cell function. Cell 99, 239–242.CrossRefGoogle Scholar
MacDonald, HB (2000) Conjugated linoleic acid and disease prevention: a review of current knowledge. Journal of the American College of Nutrition 19, 111S–118S.CrossRefGoogle ScholarPubMed
McGuire, MK, Park, YS, Behre, R, Harrison, LY, Shultz, TD & McGuire, MA (1997) Conjugated linoleic acid concentration of human milk and infant formula. Nutrition Research 17, 1277–1283.CrossRefGoogle Scholar
Mayo, MW & Baldwin, AS (2000) The transcription factor NF–kappaB: control of oncogenesis and cancer therapy resistance. Biochimica et Biophysica Acta 1470, M55–M62.Google ScholarPubMed
Meager, A (1999) Cytokine regulation of cellular adhesion molecule expression in inflammation. Cytokine & Growth Factor Reviews 10, 27–39.CrossRefGoogle ScholarPubMed
Medina, EA, Horn, WF, Keim, NL, Havel, PJ, Benito, P, Kelley, DS, Nelson, GJ & Erickson, KL (2000) Conjugated linoleic acid supplementation in humans: effects on circulating leptin concentrations and appetite. Lipids 35, 783–788.CrossRefGoogle ScholarPubMed
Miller, CC, Park, Y, Pariza, MW & Cook, ME (1994) Feeding conjugated linoleic acid to animals partially overcomes catabolic responses due to endotoxin injection. Biochemical and Biophysical Research Communications 198, 1107–1112.CrossRefGoogle ScholarPubMed
Moya-Camarena, SY & Belury, MA (1999) Species differences in the metabolism and regulation of gene expression by conjugated linoleic acid. Nutrition Reviews 57, 336–340.CrossRefGoogle Scholar
Vanden Heuvel, JP, Blanchard, SG, Leesnitzer, LA & Belury, MA (1999) Conjugated linoleic acid is a potent naturally occurring ligand and activator of PPARα. Journal of Lipid Research 40, 1426–1433.Google Scholar
Munday, JS, Thompson, KG & James, KA (1999) Dietary conjugated linoleic acids promote fatty streak formation in the C57BL/6 mouse atherosclerosis model. British Journal of Nutrition 81, 251–255.CrossRefGoogle ScholarPubMed
Nicolosi, RJ, Rogers, EJ, Kritchevsky, D, Sciemeca, JA & Huth, PJ (1997) Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolaemic hamsters. Artery 22, 266–277.Google Scholar
Niemann-Jonsson, A, Dimayuga, P, Jovinge, S, Calara, F, Ares, MP, Fredrikson, GN & Nilsson, J (2000) Accumulation of LDL in rat arteries is associated with activation of tumor necrosis factor-alpha expression. Arteriosclerosis Thrombosis and Vascular Biology 20, 2205–2211.CrossRefGoogle ScholarPubMed
Noone, E, Nugent, AP, Roche, HM & Gibney, MJ (2001) Conjugated linoleic acid – the effect of supplementation on plasma lipid metabolism. Proceedings of the Nutrition Society 60, 46A.Google Scholar
Nugent, AP, Noone, E, Gibney, MJ & Roche, HM (2000) The effect of conjugated linoleic acid on the inflammatory response in humans. Proceedings of the Nutrition Society (In the Press).Google Scholar
Olefsky, M (2000) Treatment of insulin resistance with peroxisome proliferator-activated receptor gamma agonists. Journal of Clinical Investigation 106, 467–472.CrossRefGoogle ScholarPubMed
Pariza, MW, Park, Y & Cook, ME (1999) Conjugated linoleic acid and the control of cancer and obesity. Toxicological Sciences 52, Suppl., 107–110.CrossRefGoogle ScholarPubMed
Park, Y, Albright, KJ, Liu, W, Storkson, JM, Cook, ME & Pariza, MW (1997) Effect of conjugated linoleic acid on body composition in mice. Lipids 32, 853–858.CrossRefGoogle ScholarPubMed
Park, Y, Albright, K, Liu, W, Storkson, JM, Lui, W & Pariza, MW (1999) Evidence that the trans-10, cis-12 isomer of conjugated linoleic acid induces body composition changes in mice. Lipids 34, 235–241.CrossRefGoogle ScholarPubMed
Park, Y, McGuire, MK, Behre, R, McGuire, MA, Evans, MA & Shultz, TD (1999) High–fat dairy product consumption increases Δ9c, 11t–18:2 (rumenic acid) and total lipid concentrations of human milk. Lipids 34, 543–549.CrossRefGoogle Scholar
Park, Y, Storkson, JM, Ntambi, JM, Cook, ME, Sih, CJ & Pariza, MW (2000) Inhibition of hepatic stearoyl–CoA desaturase activity by trans-10, cis-12 conjugated linoleic acid and its derivatives. Biochimica et Biophysica Acta 1486, 285–292.CrossRefGoogle ScholarPubMed
Roche, HM & Gibney, MJ (2000) The impact of postprandial lipaemia in accelerating atherothrombosis. Journal of Cardiovascular Risk 7, 317–324.CrossRefGoogle ScholarPubMed
Ronnemaa, T, Pulkki, K & Kaprio, J (2000) Serum soluble tumor necrosis factor-alpha receptor 2 is elevated in obesity but is not related to insulin sensitivity: a study in identical twins discordant for obesity. Journal of Clinical Endocrinology Metabolism 85, 2728–2732.Google Scholar
Salminen, I, Mutanen, M, Jauhiainen, M & Aro, A (1998) Dietary trans fatty acids increase conjugated linoleic acid levels in human serum. Journal of Nutrition and Biochemistry 9, 93–98.CrossRefGoogle Scholar
Sebedio, JL, Juaneda, P, Dobson, G, Ramilison, I, Martin, JC, Chardigny, JM & Christie, WW (1997) Metabolites of conjugated isomers of linoleic acid (CLA) in the rat. Biochimica et Biophysica Acta 1345, 5–10.CrossRefGoogle ScholarPubMed
Staels, B, Koenig, W, Habib, A, Merval, R, Lebret, M, Torra, IP, Delerive, P, Fadel, A, Chinetti, G, Fruchart, JC, Najib, J, Maclouf, J & Tedgui, A (1998) Activation of human aortic smooth–muscle cells is inhibited by PPARα but not PPARγ activators. Nature 393, 790–793.CrossRefGoogle Scholar
Stampfer, MJ, Krauss, RM, Ma, J, Blanche, PJ, Holl, LG, Sack, FM & Hennekens, CH (1996) A prospective study of triglyceride|level, low–density lipoprotein particle|diameter, and risk of myocardial infarction. Journal of the American Medical Association 276, 882–888.CrossRefGoogle ScholarPubMed
Su, CG, Wen, X, Bailey, ST, Jiang, W, Rangwala, SM, Keilbaugh, SA, Flanigan, A, Murthy, S, Lazar, MA & Wu, GD (1999) A novel therapy for colitis utilizing PPAR-γ ligands to inhibit the epithelial inflammatory response. Journal of Clinical Investigation 104, 383–389.CrossRefGoogle ScholarPubMed
Tontonoz, P, Nagy, L, Alvarez, JGA, Thomazy, VA & Evans, RM (1998) PPARγ promotes monocyte/macrophage differentiation and uptake of oxidised LDL. Cell 93, 241–252.CrossRefGoogle Scholar
Tsuboyama-Kasaoka, N, Takahashi, M, Tanemura, K, Kim, HJ, Tange, T, Okuyama, H, Kasai, M, Ikemoto, S & Ezaki, O (2000) Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes 49,1534–1542.CrossRefGoogle ScholarPubMed
Turek, JJ, Li, Y & Schoenlein, IA (1998) Modulation of macrophage cytokine production by conjugated linoleic acids is influenced by the dietary n-6:n-3 fatty acid ratio. Journal of Nutrition and Biochemistry 9, 258–266.CrossRefGoogle Scholar
Vanden Heuvel, JP (1999) Peroxisome proliferator–activated receptor – a critical link among fatty|acids, gene expression and carcinogenesis. Journal of Nutrition 129, 5755–5805.CrossRefGoogle ScholarPubMed
West, DB, DeLany, JP, Camet, PM, Bolhm, F, Truett, AA & Scimeca, JA (1998) Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. American Journal of Physiology 275, R667–R672.Google ScholarPubMed
Wong, MW, Chew, BP, Wong, TS, Hosick, HL, Boylston, TD & Schultz, TD (1997) Effects of dietary conjugated linoleic acid on lymphocyte function and growth of mammary tumors in mice. Anticancer Research 17, 987–994.Google ScholarPubMed
Yotosumoto, H, Hara, E, Naka, S, Adolf, RO, Emken, EA & Yanagita, T (1999) 10 trans, 12 cis–linoleic acid reduces apolipoprotein B secretion in HepG2 cells. Food Research International 31, 403–409.CrossRefGoogle Scholar
Zambell, KL, Keim, NL, Van Loan, MD, Gale, B, Benito, P, Kelley, DS & elson, GJ (2000) Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure. Lipids 35, 777–782.CrossRefGoogle ScholarPubMed