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Reviews

Conjugated linoleic acids and inflammation: isomer- and tissue-specific responses

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Pages 699-717 | Published online: 18 Jan 2017

Bibliography

  • Coussens LM, Werb Z: Inflammation and cancer. Nature 420(6917), 860–867 (2002).
  • Shoelson SE, Lee J, Goldfine AB: Inflammation and insulin resistance. J. Clin. Invest. 116(7), 1793–1801 (2006).
  • Sugimoto Y, Narumiya S: Prostaglandin E receptors. J. Biol. Chem. 282(16), 11613–11617 (2007).
  • Back M: Leukotriene receptors: crucial components in vascular inflammation.ScientificWorldJournal 7, 1422–1439 (2007).
  • Arita M, Ohira T, Sun YP, Elangovan S, Chiang N, Serhan CN: Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J. Immunol. 178(6), 3912–3917 (2007).
  • Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK: The peroxisome proliferator-activated receptor-g is a negative regulator of macrophage activation. Nature 391(6662), 79–82 (1998).
  • Kim SR, Lee KS, Park HS et al.: Involvement of IL-10 in peroxisome proliferator-activated receptor g-mediated anti-inflammatory response in asthma. Mol. Pharmacol. 68(6), 1568–1575 (2005).
  • Pascual G, Fong AL, Ogawa S et al.: A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γ. Nature 437(7059), 759–763 (2005).
  • Bagga D, Wang L, Farias-Eisner R, Glaspy JA, Reddy ST: Differential effects of prostaglandin derived from ω-6 and ω-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proc. Natl Acad. Sci. USA 100(4), 1751–1756 (2003).
  • Lee JY, Sohn KH, Rhee SH, Hwang D: Saturated fatty acids, but not unsaturated fatty acids,induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J. Biol. Chem. 276(20), 16683–16689 (2001).
  • ▪ Demonstration that fatty acids impact innate immunity.
  • Lee JY, Zhao L, Hwang DH: Modulation of pattern recognition receptor-mediated inflammation and risk of chronic diseases by dietary fatty acids. Nutr. Rev. 68(1), 38–61 (2010).
  • Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS: TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116(11), 3015–3025 (2006).
  • Wong SW, Kwon M-J, Choi AMK, Kim H-P, Nakahira K, Hwang DH: Fatty acids modulate Toll-like receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner. J. Biol. Chem. 284(40), 27384–27392 (2009).
  • Pariza MW, Ha YL: Conjugated dienoic derivatives of linoleic acid: a new class of anticarcinogens. Med. Oncol. Tumor. Pharmacother. 7(2–3), 169–171 (1990).
  • Ha YL, Grimm NK, Pariza MW: Anticarcinogens from fried ground beef: heat-altered derivatives of linoleic acid.Carcinogenesis 8(12), 1881–1887 (1987).
  • ▪ First demonstration of the biological activities of conjugated linoleic acid (CLA).
  • Wahle KW, Heys SD, Rotondo D: Conjugated linoleic acids: are they beneficial or detrimental to health? Prog. Lipid Res. 43(6), 553–587 (2004).
  • Rainer L, Heiss CJ: Conjugated linoleic acid: health implications and effects on body composition. J. Am. Diet. Assoc. 104(6), 963–968; quiz 1032 (2004).
  • Pariza MW, Park Y, Cook ME: The biologically active isomers of conjugated linoleic acid. Prog. Lipid. Res. 40(4), 283–298 (2001).
  • Whigham LD, Cook ME, Atkinson RL: Conjugated linoleic acid: implications for human health. Pharmacol. Res. 42(6), 503–510 (2000).
  • Kelly GS: Conjugated linoleic acid: a review. Altern. Med. Rev. 6(4), 367–382 (2001).
  • Lock AL, Bauman DE: Modifying milk fat composition of dairy cows to enhance fatty acids beneficial to human health. Lipids 39(12), 1197–1206 (2004).
  • Yurawecz MP: Advances in Conjugated Linoleic Acid Research. AOCS Press, IL, USA (1999).
  • Martins SV, Lopes PA, Alfaia CM et al.: Contents of conjugated linoleic acid isomers in ruminant-derived foods and estimation of their contribution to daily intake in Portugal.Br. J. Nutr. 98(6), 1206–1213 (2007).
  • Tsuzuki T, Ikeda I: Slow absorption of conjugated linoleic acid in rat intestines, and similar absorption rates of 9c,11t-conjugated linoleic acid and 10t,12c-conjugated linoleic acid. Biosci. Biotechnol. Biochem. 71(8), 2034–2040 (2007).
  • Emken EA, Adlof RO, Duval S, Nelson G, Benito P: Effect of dietary conjugated linoleic acid (CLA) on metabolism of isotope-labeled oleic, linoleic, and CLA isomers in women.Lipids 37(8), 741–750 (2002).
  • Petridou A, Mougios V, Sagredos A: Supplementation with CLA: isomer incorporation into serum lipids and effect on body fat of women. Lipids 38(8), 805–811 (2003).
  • Burdge GC, Derrick PR, Russell JJ et al.: Incorporation of cis-9, trans-11 or trans-10, cis-12 conjugated linoleic acid into human erythrocytes in vivo. Nutr. Res. 25(1), 13–19 (2005).
  • Burdge GC, Lupoli B, Russell JJ et al.: Incorporation of cis-9,trans-11 or trans-10,cis-12 conjugated linoleic acid into plasma and cellular lipids in healthy men.J. Lipid Res. 45(4), 736–741 (2004).
  • Kelley DS, Bartolini GL, Newman JW, Vemuri M, Mackey BE: Fatty acid composition of liver, adipose tissue, spleen, and heart of mice fed diets containing t10, c12-, and c9, t11-conjugated linoleic acid.Prostaglandins Leukot. Essent. Fatty Acids 74(5), 331–338 (2006).
  • Choi Y, Kim YC, Han YB, Park Y, Pariza MW, Ntambi JM: The trans-10,cis-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes. J. Nutr. 130(8), 1920–1924 (2000).
  • Choi Y, Park Y, Pariza MW, Ntambi JM: Regulation of stearoyl-coA desaturase activity by the trans-10,cis-12 isomer of conjugated linoleic acid in HepG2 cells. Biochem. Biophys. Res. Commun. 284(3), 689–693 (2001).
  • Lee KN, Pariza MW, Ntambi JM: Conjugated linoleic acid decreases hepatic stearoyl-coA desaturase mRNA expression.Biochem. Biophys. Res. Commun. 248(3), 817–821 (1998).
  • Smedman A, Vessby B: Conjugated linoleic acid supplementation in humans – metabolic effects. Lipids 36(8), 773–781 (2001).
  • Banni S, Petroni A, Blasevich M et al.: Conjugated linoleic acids (CLA) as precursors of a distinct family of PUFA. Lipids 39(11), 1143–1146 (2004).
  • Banni S, Carta G, Angioni E et al.: Distribution of conjugated linoleic acid and metabolites in different lipid fractions in the rat liver. J. Lipid Res. 42(7), 1056–1061 (2001).
  • Lucchi L, Banni S, Melis MP et al.: Changes in conjugated linoleic acid and its metabolites in patients with chronic renal failure. Kidney Int. 58(4), 1695–1702 (2000).
  • Cook ME, Miller CC, Park Y, Pariza M: Immune modulation by altered nutrient metabolism: nutritional control of immune- induced growth depression. Poult. Sci. 72(7), 1301–1305 (1993).
  • Miller CC, Park Y, Pariza MW, Cook ME: Feeding conjugated linoleic acid to animals partially overcomes catabolic responses due to endotoxin injection. Biochem. Biophys. Res. Commun. 198(3), 1107–1112 (1994).
  • Wong MW, Chew BP, Wong TS, Hosick HL, Boylston TD, Shultz TD: Effects of dietary conjugated linoleic acid on lymphocyte function and growth of mammary tumors in mice. Anticancer Res. 17(2A), 987–993 (1997).
  • Hayek MG, Han SN, Wu D et al.: Dietary conjugated linoleic acid influences the immune response of young and old C57BL/6NCrlBR mice. J. Nutr. 129(1), 32–38 (1999).
  • Rahman MM, Bhattacharya A, Banu J, Fernandes G: Conjugated linoleic acid protects against age-associated bone loss in C57BL/6 female mice. J. Nutr. Biochem. 18(7), 467–474 (2007).
  • Kelley DS, Warren JM, Simon VA, Bartolini G, Mackey BE, Erickson KL: Similar effects of c9,t11-CLA and t10,c12- CLA on immune cell functions in mice.Lipids 37(7), 725–728 (2002).
  • Song HJ, Grant I, Rotondo D et al.: Effect of CLA supplementation on immune function in young healthy volunteers. Eur. J. Clin. Nutr. 59(4), 508–517 (2005).
  • Albers R, Van Der Wielen RP, Brink EJ, Hendriks HF, Dorovska-Taran VN, Mohede IC: 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. 57(4), 595–603 (2003).
  • Tricon S, Burdge GC, Kew S et al.: Effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on immune cell function in healthy humans. Am. J. Clin. Nutr. 80(6), 1626–1633 (2004).
  • Nugent AP, Roche HM, Noone EJ, Long A, Kelleher DK, Gibney MJ: The effects of conjugated linoleic acid supplementation on immune function in healthy volunteers.Eur. J. Clin. Nutr. 59(6), 742–750 (2005).
  • Ramakers JD, Plat J, Sebedio JL, Mensink RP: Effects of the individual isomers cis-9,trans-11 vs. trans-10,cis-12 of conjugated linoleic acid (CLA) on inflammation parameters in moderately overweight subjects with LDL-phenotype B. Lipids 40(9), 909–918 (2005).
  • Ritzenthaler KL, Mcguire MK, Mcguire MA et al.: Consumption of conjugated linoleic acid (CLA) from CLA-enriched cheese does not alter milk fat or immunity in lactating women. J. Nutr. 135(3), 422–430 (2005).
  • Kelley DS, Taylor PC, Rudolph IL et al.: Dietary conjugated linoleic acid did not alter immune status in young healthy women.Lipids 35(10), 1065–1071 (2000).
  • Yu Y, Correll PH, Vanden Heuvel JP: Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPAR γ-dependent mechanism. Biochim. Biophys. Acta 1581(3), 89–99 (2002).
  • Luongo D, Bergamo P, Rossi M: Effects of conjugated linoleic acid on growth and cytokine expression in Jurkat T cells.Immunol. Lett. 90(2–3), 195–201 (2003).
  • Loscher CE, Draper E, Leavy O, Kelleher D, Mills KH, Roche HM: Conjugated linoleic acid suppresses NF-κ B activation and IL-12 production in dendritic cells through ERK-mediated IL-10 induction. J. Immunol. 175(8), 4990–4998 (2005).
  • ▪ Details effects of the mechanism and signaling of CLA.
  • Li Y, Watkins BA: Conjugated linoleic acids alter bone fatty acid composition and reduce ex vivo prostaglandin E2 biosynthesis in rats fed n-6 or n-3 fatty acids. Lipids 33(4), 417–425 (1998).
  • Sugano M, Tsujita A, Yamasaki M, Noguchi M, Yamada K: Conjugated linoleic acid modulates tissue levels of chemical mediators and immunoglobulins in rats.Lipids 33(5), 521–527 (1998).
  • Lee Y, Thompson JT, Vanden Heuvel JP: 9E,11E-conjugated linoleic acid increases expression of the endogenous antiinflammatory factor, interleukin-1 receptor antagonist, in RAW 264.7 cells.J. Nutr. 139(10), 1861–1866 (2009).
  • Whigham LD, Cook EB, Stahl JL et al.: CLA reduces antigen-induced histamine and PGE2 release from sensitized guinea pig tracheae. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280(3), R908–R912 (2001).
  • Stachowska E, Dziedziejko V, Safranow K et al.: Inhibition of phospholipase A2 activity by conjugated linoleic acids in human macrophages. Eur. J. Nutr. 46(1), 28–33 (2007).
  • Eder K, Schleser S, Becker K, Korting R: Conjugated linoleic acids lower the release of eicosanoids and nitric oxide from human aortic endothelial cells. J. Nutr. 133(12), 4083–4089 (2003).
  • Stachowska E, Dziedziejko V, Safranow K et al.: Effect of conjugated linoleic acids on the activity and mRNA expression of 5- and 15-lipoxygenases in human macrophages.J. Agric. Food Chem. 55(13), 5335–5342 (2007).
  • Olefsky JM: Nuclear receptor minireview series. J. Biol. Chem. 276(40), 36863–36864 (2001).
  • Cuzzocrea S, Pisano B, Dugo L et al.: Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-γ, reduces acute inflammation. Eur. J. Pharmacol. 483(1), 79–93 (2004).
  • Roche HM, Noone E, Sewter C et al.: Isomer-dependent metabolic effects of conjugated linoleic acid:insights from molecular markers sterol regulatory element-binding protein-1c and LXRα.Diabetes 51(7), 2037–2044 (2002).
  • ▪ Isomer-specific action of CLA on SREBP1c and liver X receptor α transcription factor regulation.
  • Navarro MA, Badimon L, Rodriguez C et al.: Trans-10,cis-12-CLA dysregulate lipid and glucose metabolism and induce hepatic NR4A receptors. Front. Biosci. (Elite Ed.) 2, 87–97 (2010).
  • Cheng W-L, Lii C-K, Chen H-W, Lin T-H, Liu K-L: Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-κB pathway. J. Agric. Food Chem. 52(1), 71–78 (2003).
  • Ringseis R, Gahler S, Eder K: Conjugated linoleic acid isomers inhibit platelet-derived growth factor-induced NF-κB transactivation and collagen formation in human vascular smooth muscle cells. Eur. J. Nutr. 47(2), 59–67 (2008).
  • Li G, Barnes D, Butz D, Bjorling D, Cook ME: 10t,12c-conjugated linoleic acid inhibits lipopolysaccharide-induced cyclooxygenase expression in vitro and in vivo. J. Lipid Res. 46(10), 2134–2142 (2005).
  • Ross R: Atherosclerosis – an inflammatory disease. N. Engl. J. Med. 340(2), 115–126 (1999).
  • ▪▪ Excellent review of the the inflammatory aspects of atherosclerosis.
  • Glass CK, Witztum JL: Atherosclerosis. the road ahead. Cell 104(4), 503–516 (2001).
  • ▪▪ Excellent review of atherosclerosis and its relationship to inflammation.
  • Eder K, Ringseis R: Metabolism and actions of conjugated linoleic acids on atherosclerosis- related events in vascular endothelial cells and smooth muscle cells. Mol. Nutr. Food Res. 54(1), 17–36 (2010).
  • Lusis AJ: Atherosclerosis. Nature 407(6801), 233–241 (2000).
  • Weldon S, Mitchell S, Kelleher D, Gibney MJ, Roche HM: Conjugated linoleic acid and atherosclerosis: no effect on molecular markers of cholesterol homeostasis in THP-1 macrophages. Atherosclerosis 174(2), 261–273 (2004).
  • Mcclelland S, Cox C, O’connor R et al.: Conjugated linoleic acid suppresses the migratory and inflammatory phenotype of the monocyte/macrophage cell. Atherosclerosis 211(1), 96–102 (2010).
  • Sneddon AA, Mcleod E, Wahle KW, Arthur JR: Cytokine-induced monocyte adhesion to endothelial cells involves platelet-activating factor: suppression by conjugated linoleic acid. Biochim. Biophys. Acta 1761(7), 793–801 (2006).
  • Coen P, Cummins P, Birney Y, Devery R, Cahill P: Modulation of nitric oxide and 6-keto-prostaglandin F1α production in bovine aortic endothelial cells by conjugated linoleic acid. Endothelium 11(3–4), 211–220 (2004).
  • Schleser S, Ringseis R, Eder K: Conjugated linoleic acids have no effect on TNFa-induced adhesion molecule expression, U937 monocyte adhesion, and chemokine release in human aortic endothelial cells. Atherosclerosis 186(2), 337–344 (2006).
  • Lee Y, Vanden Heuvel JP: Inhibition of macrophage adhesion activity by 9trans,11trans-conjugated linoleic acid.J. Nutr. Biochem. 21(6), 490–497 (2009).
  • Ringseis R, Muller A, Herter C, Gahler S, Steinhart H, Eder K: CLA isomers inhibit TNFα-induced eicosanoid release from human vascular smooth muscle cells via a PPARg ligand-like action. Biochim. Biophys. Acta 1760(2), 290–300 (2006).
  • Munday JS, Thompson KG, James KA: Dietary conjugated linoleic acids promote fatty streak formation in the C57BL/6 mouse atherosclerosis model. Br J. Nutr. 81(3), 251–255 (1999).
  • Nicolosi RJ, Rogers EJ, Kritchevsky D, Scimeca JA, Huth PJ: Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters. Artery 22(5), 266–277 (1997).
  • Wilson TA, Nicolosi RJ, Saati A, Kotyla T, Kritchevsky D: Conjugated linoleic acid isomers reduce blood cholesterol levels but not aortic cholesterol accumulation in hypercholesterolemic hamsters. Lipids 41(1), 41–48 (2006).
  • Lee KN, Kritchevsky D, Pariza MW: Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis 108(1), 19–25 (1994).
  • Reza JZ, Doosti M, Salehipour M, Packnejad M, Mojarrad M, Heidari M: Modulation peroxisome proliferators activated receptor a (PPAR a) and acyl coenzyme A: cholesterol acyltransferase1 (ACAT1) gene expression by fatty acids in foam cell. Lipids Health Dis. 8, 38 (2009).
  • Valeille K, Ferezou J, Amsler G et al.: A cis-9,trans-11-conjugated linoleic acid-rich oil reduces the outcome of atherogenic process in hyperlipidemic hamster. Am. J. Physiol. Heart Circ. Physiol. 289(2), H652–H659 (2005).
  • Herrmann J, Rubin D, Hasler R et al.: Isomer-specific effects of CLA on gene expression in human adipose tissue depending on PPARγ2 P12A polymorphism: a double blind, randomized, controlled cross-over study.Lipids Health Dis. 8, 35 (2009).
  • Park Y, Storkson JM, Albright KJ, Liu W, Pariza MW: Biological activities of conjugated fatty acids: conjugated eicosadienoic (conj. 20:2δ(c11,t13/t12,c14)), eicosatrienoic (conj. 20:3delta(c8,t12,c14)), and heneicosadienoic (conj. 21:2δ(c12,t14/c13,t15)) acids and other metabolites of conjugated linoleic acid. Biochim. Biophys. Acta 1687(1–3), 120–129 (2005).
  • Bulgarella JA, Patton D, Bull AW: Modulation of prostaglandin H synthase activity by conjugated linoleic acid (CLA) and specific CLA isomers. Lipids 36(4), 407–412 (2001).
  • Wang P, Mariman E, Renes J, Keijer J: The secretory function of adipocytes in the physiology of white adipose tissue. J. Cell. Physiol. 216(1), 3–13 (2008).
  • Berg AH, Combs TP, Du X, Brownlee M, Scherer PE: The adipocyte-secreted protein Acrp30 enhances hepatic insulin action.Nat. Med. 7(8), 947–953 (2001).
  • Yamauchi T, Kamon J, Waki H et al.: The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7(8), 941–946 (2001).
  • Fried SK, Bunkin DA, Greenberg AS: Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J. Clin. Endocrinol. Metab. 83(3), 847–850 (1998).
  • Weisberg SP, Mccann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW: Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112(12), 1796–1808 (2003).
  • Chen Y, Zhu J, Lum PY et al.: Variations in DNA elucidate molecular networks that cause disease. Nature 452(7186), 429–435 (2008).
  • Schenk S, Saberi M, Olefsky JM: Insulin sensitivity: modulation by nutrients and inflammation. J. Clin. Invest. 118(9), 2992–3002 (2008).
  • ▪▪ Interesting review that ties together the role of fatty acid excess, endoplasmic reticulum stress and inflammation in insulin resistance.
  • Park Y, Albright KJ, Liu W, Storkson JM, Cook ME, Pariza MW: Effect of conjugated linoleic acid on body composition in mice. Lipids 32(8), 853–858 (1997).
  • ▪ First demonstration of the dramatic effect of conjugated linoleic acids on adipose.
  • Terpstra AH, Beynen AC, Everts H, Kocsis S, Katan MB, Zock PL: The decrease in body fat in mice fed conjugated linoleic acid is due to increases in energy expenditure and energy loss in the excreta. J. Nutr. 132(5), 940–945 (2002).
  • Tsuboyama-Kasaoka N, Takahashi M, Tanemura K et al.: Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice.Diabetes 49(9), 1534–1542 (2000).
  • ▪ Early demonstration of the detrimental effects of CLA on adipose tissue.
  • Poirier H, Shapiro JS, Kim RJ, Lazar MA: Nutritional supplementation with trans-10, cis-12-conjugated linoleic acid induces inflammation of white adipose tissue. Diabetes 55(6), 1634–1641 (2006).
  • ▪▪ First demonstration that the effects of CLA in adipose tissue are related to inflammation and macrophage recruitment into adipose tissue.
  • Clement L, Poirier H, Niot I et al.: Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. J. Lipid Res. 43(9), 1400–1409 (2002).
  • Riserus U, Basu S, Jovinge S, Fredrikson GN, Arnlov J, Vessby B: Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein: a potential link to fatty acid-induced insulin resistance. Circulation 106(15), 1925–1929 (2002).
  • Brown JM, Halvorsen YD, Lea-Currie YR, Geigerman C, Mcintosh M: Trans-10, cis-12, but not cis-9, trans-11, conjugated linoleic acid attenuates lipogenesis in primary cultures of stromal vascular cells from human adipose tissue. J. Nutr. 131(9), 2316–2321 (2001).
  • Moloney F, Toomey S, Noone E et al.: Antidiabetic effects of cis-9, trans-11- conjugated linoleic acid may be mediated via anti-inflammatory effects in white adipose tissue. Diabetes 56(3), 574–582 (2007).
  • 9cis (Z),11trans (E)-CLA’s effects may act counter to 10E,12Z-CLA when administered independently.
  • Tricon S, Burdge GC, Kew S et al.: Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans. Am. J. Clin. Nutr. 80(3), 614–620 (2004).
  • Degrace P, Demizieux L, Gresti J, Chardigny JM, Sebedio JL, Clouet P: Association of liver steatosis with lipid oversecretion and hypotriglyceridaemia in C57BL/6J mice fed trans-10,cis-12-linoleic acid. FEBS Lett. 546(2–3), 335–339 (2003).
  • Degrace P, Moindrot B, Mohamed I et al.: Upregulation of liver VLDL receptor and FAT/CD36 expression in LDLR-1- apoB100/100 mice fed trans-10,cis-12 conjugated linoleic acid. J. Lipid Res. 47(12), 2647–2655 (2006).
  • Halade GV, Rahman MM, Fernandes G: Differential effects of conjugated linoleic acid isomers in insulin-resistant female C57Bl/6J mice. J. Nutr. Biochem. 21(4), 332–337 (2010).
  • Jourdan T, Djaouti L, Demizieux L, Gresti J, Verges B, Degrace P: Liver carbohydrate and lipid metabolism of insulin-deficient mice is altered by trans-10, cis-12 conjugated linoleic acid. J. Nutr. 139(10), 1901–1907 (2009).
  • Liu L-F, Purushotham A, Wendel AA, Belury MA: Combined effects of rosiglitazone and conjugated linoleic acid on adiposity, insulin sensitivity, and hepatic steatosis in high-fat-fed mice. Am. J. Physiol. Gastrointest. Liver Physiol. 292(6), G1671–G1682 (2007).
  • Cooper MH, Miller JR, Mitchell PL, Currie DL, Mcleod RS: Conjugated linoleic acid isomers have no effect on atherosclerosis and adverse effects on lipoprotein and liver lipid metabolism in APOE-1- mice fed a high-cholesterol diet. Atherosclerosis 200(2), 294–302 (2008).
  • Russell JS, Mcgee SO, Ip MM, Kuhlmann D, Masso-Welch PA: Conjugated linoleic acid induces mast cell recruitment during mouse mammary gland stromal remodeling. J. Nutr. 137(5), 1200–1207 (2007).
  • Patsouris D, Li P-P, Thapar D, Chapman J, Olefsky JM, Neels JG: Ablation of CD11c- positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab. 8(4), 301–309 (2008).
  • Silveira MB, Carraro R, Monereo S, Tebar J: Conjugated linoleic acid (CLA) and obesity.Public Health Nutr. 10(10A), 1181–1186 (2007).
  • Whigham LD, Watras AC, Schoeller DA: Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans.Am. J. Clin. Nutr. 85(5), 1203–1211 (2007).
  • Riserus U, Arner P, Brismar K, Vessby B: Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care 25(9), 1516–1521 (2002).
  • ▪ Early demonstration that the 10E12Z isomer has detrimental effects in humans as well as animals.
  • Ramos R, Mascarenhas J, Duarte P, Vicente C, Casteleiro C: Conjugated linoleic acid-induced toxic hepatitis: first case report.Dig. Dis. Sci. 54(5), 1141–1143 (2009).
  • Basu S, Riserus U, Turpeinen A, Vessby B: Conjugated linoleic acid induces lipid peroxidation in men with abdominal obesity.Clin. Sci. 99(6), 511–516 (2000).
  • Thrush AB, Chabowski A, Heigenhauser GJ, Mcbride BW, Or-Rashid M, Dyck DJ: Conjugated linoleic acid increases skeletal muscle ceramide content and decreases insulin sensitivity in overweight, non-diabetic humans. Appl. Physiol. Nutr. Metab. 32(3), 372–382 (2007).
  • Gaullier JM, Halse J, Hoivik HO et al.: Six months supplementation with conjugated linoleic acid induces regional-specific fat mass decreases in overweight and obese. Br. J. Nutr. 97(3), 550–560 (2007).
  • Granlund L, Juvet LK, Pedersen JI, Nebb HI: Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARg modulator.J. Lipid Res. 44(8), 1441–1452 (2003).
  • Kang K, Liu W, Albright KJ, Park Y, Pariza MW: Trans-10,cis-12 CLA inhibits differentiation of 3T3-L1 adipocytes and decreases PPAR γ expression. Biochem. Biophys. Res. Commun. 303(3), 795–799 (2003).
  • Evans M, Park Y, Pariza M, Curtis L, Kuebler B, Mcintosh M: Trans-10,cis-12 conjugated linoleic acid reduces triglyceride content while differentially affecting peroxisome proliferator activated receptor g2 and aP2 expression in 3T3-L1 preadipocytes.Lipids 36(11), 1223–1232 (2001).
  • Evans M, Geigerman C, Cook J, Curtis L, Kuebler B, Mcintosh M: Conjugated linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3T3-L1 preadipocytes. Lipids 35(8), 899–910 (2000).
  • Brown JM, Boysen MS, Chung S et al.: Conjugated linoleic acid induces human adipocyte delipidation: autocrine/paracrine regulation of MEK/ERK signaling by adipocytokines. J. Biol. Chem. 279(25), 26735–26747 (2004).
  • Chung S, Brown JM, Provo JN, Hopkins R, Mcintosh MK: Conjugated linoleic acid promotes human adipocyte insulin resistance through NF{κ}B-dependent cytokine production. J. Biol. Chem. 280(46), 38445–38456 (2005).
  • ▪▪ Demonstrates that NF-κB plays a signficant role in inducing both inflammatory and insulin resistance responses to 10E,12Z-CLA in human adipocytes .
  • Evans M, Lin X, Odle J, Mcintosh M: Trans-10, cis-12 conjugated linoleic acid increases fatty acid oxidation in 3T3-L1 preadipocytes. J. Nutr. 132(3), 450–455 (2002).
  • Tsuboyama-Kasaoka N, Miyazaki H, Kasaoka S, Ezaki O: Increasing the amount of fat in a conjugated linoleic acid-supplemented diet reduces lipodystrophy in mice. J. Nutr. 133(6), 1793–1799 (2003).
  • Subbaiah PV, Sircar D, Aizezi B, Mintzer E: Differential effects of conjugated linoleic acid isomers on the biophysical and biochemical properties of model membranes. Biochim. Biophys. Acta 1798(3), 506–514 (2010).
  • Vainio S, Bykov I, Hermansson M, Jokitalo E, Somerharju P, Ikonen E: Defective insulin receptor activation and altered lipid rafts in Niemann–Pick type C disease hepatocytes. Biochem. J. 391(Pt 3), 465–472 (2005).
  • Larosa PC, Riethoven JJ, Chen H et al.: Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes. Physiol. Genomics 31(3), 544–553 (2007).
  • Wek RC, Jiang H-Y, Anthony TG: Coping with stress: eIF2 kinases and translational control. Biochem. Soc. Trans. 34(Pt 1), 7–11 (2006).
  • Ozcan U, Cao Q, Yilmaz E et al.: Endoplasmic reticulum stress links obesity, insulin action, and Type 2 diabetes. Science 306(5695), 457–461 (2004).
  • ▪▪ Details functional links between endoplasmic reticulum stress and insulin sensitivity in adipose tissue.
  • Gregor MF, Hotamisligil GS: Thematic review series: adipocyte biology. Adipocyte stress: the endoplasmic reticulum and metabolic disease. J. Lipid Res. 48(9), 1905–1914 (2007).
  • Ariyama H, Kono N, Matsuda S, Inoue T, Arai H: Decrease in membrane phospholipid unsaturation induces unfolded protein response. J. Biol. Chem. 285(29), 22027–22035 (2010).
  • Ou L, Wu Y, Ip C, Meng X, Hsu Y-C, Ip MM: Apoptosis induced by t10,c12- conjugated linoleic acid is mediated by an atypical endoplasmic reticulum stress response. J. Lipid Res. 49(5), 985–994 (2008).
  • Kennedy A, Martinez K, Chung S et al.: Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid are dependent on intracellular calcium levels in primary cultures of human adipocytes.J. Lipid Res. 51(7), 1906–1917 (2010).
  • Peters JM, Park Y, Gonzalez FJ, Pariza MW: Influence of conjugated linoleic acid on body composition and target gene expression in peroxisome proliferator-activated receptor α-null mice. Biochim. Biophys. Acta 1533(3), 233–242 (2001).
  • Necela BM, Su W, Thompson EA: Toll-like receptor 4 mediates cross-talk between peroxisome proliferator-activated receptor g and nuclear factor-κB in macrophages.Immunology 125(3), 344–358 (2008).
  • Chae GN, Kwak SJ: NF-κB is involved in the TNF-α induced inhibition of the differentiation of 3T3-L1 cells by reducing PPARγ expression. Exp. Mol. Med. 35(5), 431–437 (2003).
  • Adams M, Reginato MJ, Shao D, Lazar MA, Chatterjee VK: Transcriptional activation by peroxisome proliferator-activated receptor γ is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site. J. Biol. Chem. 272(8), 5128–5132 (1997).
  • Kennedy A, Chung S, Lapoint K, Fabiyi O, Mcintosh MK: Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARγ activity in primary cultures of human adipocytes. J. Nutr. 138(3), 455–461 (2008).
  • Mcgillicuddy FC, Chiquoine EH, Hinkle CC et al.: Interferon γ attenuates insulin signaling, lipid storage, and differentiation in human adipocytes via activation of the JAK/STAT pathway. J. Biol. Chem. 284(46), 31936–31944 (2009).
  • Hotamisligil GS, Shargill NS, Spiegelman BM: Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science 259(5091), 87–91 (1993).
  • ▪▪ Demonstrates the inflammatory capacity of adipose tissue and its ability to secrete cytokines such as TNF-α in obesity and insulin resistance.
  • Larosa PC, Miner J, Xia Y, Zhou Y, Kachman S, Fromm ME: Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis.Physiol. Genomics 27(3), 282–294 (2006).
  • Kennedy A, Overman A, Lapoint K et al.: Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol.J. Lipid Res. 50(2), 225–232 (2009).
  • Serrero G, Lepak NM, Goodrich SP: Paracrine regulation of adipose differentiation by arachidonate metabolites: prostaglandin F2 α inhibits early and late markers of differentiation in the adipogenic cell line 1246. Endocrinology 131(6), 2545–2551 (1992).
  • Arnould T, Thibaut-Vercruyssen R, Bouaziz N, Dieu M, Remacle J, Michiels C: PGF2α, a prostanoid released by endothelial cells activated by hypoxia, is a chemoattractant candidate for neutrophil recruitment. Am. J. Pathol. 159(1), 345–357 (2001).
  • Serrero G, Lepak NM, Goodrich SP: Prostaglandin-F2 α inhibits the differentiation of adipocyte precurssors in primary culture. Biochem. Biophys. Res. Commun. 183(2), 438–442 (1992).
  • Stachowska E, Dolegowska B, Dziedziejko V et al.: Prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) synthesis is regulated by conjugated linoleic acids (CLA) in human macrophages. J. Physiol. Pharmacol. 60(1), 77–85 (2009).
  • Politis I, Dimopoulou M, Voudouri A, Noikokyris P, Feggeros K: Effects of dietary conjugated linoleic acid isomers on several functional properties of macrophages and heterophils in laying hens. Br. Poult. Sci. 44(2), 203–210 (2003).
  • Bassaganya-Riera J, Hontecillas-Magarzo R, Bregendahl K, Wannemuehler MJ, Zimmerman DR: Effects of dietary conjugated linoleic acid in nursery pigs of dirty and clean environments on growth, empty body composition, and immune competence. J. Anim. Sci. 79(3), 714–721 (2001).
  • Yamasaki M, Chujo H, Hirao A et al.: Immunoglobulin and cytokine production from spleen lymphocytes is modulated in C57BL/6J mice by dietary cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid.J. Nutr. 133(3), 784–788 (2003).
  • Turini ME, Boza JJ, Gueissaz N et al.: Short-term dietary conjugated linoleic acid supplementation does not enhance the recovery of immunodepleted dexamethasone-treated rats. Eur. J. Nutr. 42(3), 171–179 (2003).
  • Ruth MR, Taylor CG, Zahradka P, Field CJ: Abnormal immune responses in fa/fa Zucker rats and effects of feeding conjugated linoleic acid. Obesity 16(8), 1770–1779 (2008).
  • Evans NP, Misyak SA, Schmelz EM, Guri AJ, Hontecillas R, Bassaganya-Riera J: Conjugated linoleic acid ameliorates inflammation-induced colorectal cancer in mice through activation of PPARγ. J. Nutr. 140(3), 515–521 (2010).
  • Reynolds CM, Draper E, Keogh B et al.: A conjugated linoleic acid-enriched beef diet attenuates lipopolysaccharide-induced inflammation in mice in part through PPARg-mediated suppression of toll-like receptor 4. J. Nutr. 139(12), 2351–2357 (2009).
  • Parra P, Palou A, Serra F: Moderate doses of conjugated linoleic acid reduce fat gain, maintain insulin sensitivity without impairing inflammatory adipose tissue status in mice fed a high-fat diet. Nutr. Metab. 7, 5 (2010).
  • Kritchevsky D, Tepper SA, Wright S, Tso P, Czarnecki SK: Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits.J. Am. Coll. Nutr. 19(4), 472S–477S (2000).
  • Park Y, Albright KJ, Storkson JM, Liu W, Cook ME, Pariza MW: Changes in body composition in mice during feeding and withdrawal of conjugated linoleic acid. Lipids 34(3), 243–248 (1999).
  • Mitchell PL, Langille MA, Currie DL, Mcleod RS: Effect of conjugated linoleic acid isomers on lipoproteins and atherosclerosis in the Syrian golden hamster. Biochim. Biophys. Acta 1734(3), 269–276 (2005).
  • Arbones-Mainar JM, Navarro MA, Guzman MA et al.: Selective effect of conjugated linoleic acid isomers on atherosclerotic lesion development in apolipoprotein E knockout mice.Atherosclerosis 189(2), 318–327 (2006).
  • Nestel P, Fujii A, Allen T: The cis-9,trans-11 isomer of conjugated linoleic acid (CLA) lowers plasma triglyceride and raises HDL cholesterol concentrations but does not suppress aortic atherosclerosis in diabetic apoE-deficient mice. Atherosclerosis 189(2), 282–287 (2006).
  • Toomey S, Harhen B, Roche HM, Fitzgerald D, Belton O: Profound resolution of early atherosclerosis with conjugated linoleic acid. Atherosclerosis 187(1), 40–49 (2006).
  • Navarro V, Macarulla MT, Fernandez-Quintela A, Rodriguez VM, Simon E, Portillo MP: Effects of trans-10,cis-12 conjugated linoleic acid on cholesterol metabolism in hypercholesterolaemic hamsters.Eur. J. Nutr. 46(4), 213–219 (2007).
  • Kelley DS, Vemuri M, Adkins Y, Gill SH, Fedor D, Mackey BE: Flaxseed oil prevents trans-10, cis-12-conjugated linoleic acid- induced insulin resistance in mice. Br. J. Nutr. 101(5), 701–708 (2009).
  • Benito P, Nelson GJ, Kelley DS, Bartolini G, Schmidt PC, Simon V: The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans. Lipids 36(3), 229–236 (2001).
  • Mougios V, Matsakas A, Petridou A et al.: Effect of supplementation with conjugated linoleic acid on human serum lipids and body fat. J. Nutr. Biochem 12(10), 585–594 (2001).
  • Gaullier JM, Halse J, Hoye K et al.: Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Am. J. Clin. Nutr. 79(6), 1118–1125 (2004).
  • Desroches S, Chouinard PY, Galibois I et al.: Lack of effect of dietary conjugated linoleic acids naturally incorporated into butter on the lipid profile and body composition of overweight and obese men. Am. J. Clin. Nutr. 82(2), 309–319 (2005).
  • Raff M, Tholstrup T, Basu S, Nonboe P, Sorensen MT, Straarup EM: A diet rich in conjugated linoleic acid and butter increases lipid peroxidation but does not affect atherosclerotic, inflammatory, or diabetic risk markers in healthy young men. J. Nutr. 138(3), 509–514 (2008).
  • Sluijs I, Plantinga Y, De Roos B, Mennen LI, Bots ML: Dietary supplementation with cis-9,trans-11 conjugated linoleic acid and aortic stiffness in overweight and obese adults. Am. J. Clin. Nutr. 91(1), 175–183 (2010).

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