1932

Abstract

Obesity is the most widespread nutritional disease in the United States. Developing effective and safe strategies to manage excess body weight is therefore of paramount importance. One potential strategy to reduce obesity is to consume conjugated linoleic acid (CLA) supplements containing isomers -9-11 and -10-12, or -10, 12 alone. Proposed antiobesity mechanisms of CLA include regulation of () adipogenesis, () lipid metabolism, () inflammation, () adipocyte apoptosis, () browning or beiging of adipose tissue, and () energy metabolism. However, causality of CLA-mediated responses to body fat loss, particularly the linkage between inflammation, thermogenesis, and energy metabolism, is unclear. This review examines whether CLA's antiobesity properties are due to inflammatory signaling and considers CLA's linkage with lipogenesis, lipolysis, thermogenesis, and browning of white and brown adipose tissue. We propose a series of questions and studies to interrogate the role of the sympathetic nervous system in mediating CLA's antiobesity properties.

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2016-07-17
2024-06-15
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Literature Cited

  1. Agatha G, Voigt A, Kauf E, Zintl F. 1.  2004. Conjugated linoleic acid modulation of cell membrane in leukemia cells. Cancer Lett. 209:187–103 [Google Scholar]
  2. Almind K, Manieri K, Sivitz W, Cinti S, Kahn CR. 2.  2007. Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice. PNAS 104:2366–71 [Google Scholar]
  3. Amisten S, Neville M, Hawkes R, Persaud SJ, Karpe F, Salehi A. 3.  2015. An atlas of G-protein coupled receptor expression and function in human subcutaneous adipose tissue. Pharmacol. Ther. 146:61–93 [Google Scholar]
  4. Bachman ES, Dhillon H, Zhang CY, Cinti S, Bianco AC. 4.  et al. 2002. betaAR signaling required for diet-induced thermogenesis and obesity resistance. Science 297:843–45 [Google Scholar]
  5. Bamshad M, Aoki VT, Adkison MG, Warren WS, Bartness TJ. 5.  1998. Central nervous system origins of the sympathetic nervous system outflow to white adipose tissue. Am. J. Physiol. 275:R291–99 [Google Scholar]
  6. Banni S, Angioni E, Murru E, Carta G, Melis MP. 6.  et al. 2001. Vaccenic acid feeding increases tissue levels of conjugated linoleic acid and suppresses development of premalignant lesions in rat mammary gland. Nutr. Cancer 41:1–291–97 [Google Scholar]
  7. Bartness T, Liu Y, Shrestha Y, Ryu V. 7.  2014. Neural innervation of white adipose tissue and the control of lipolysis. Front. Neuroendocrinol. 35:4473–93 [Google Scholar]
  8. Bartness T, Ryu V. 8.  2015. Neural control of white, beige, and brown adipocytes. Int. J. Obesity Suppl. 5:S35–39 [Google Scholar]
  9. Bartness TJ, Vaughan CH, Song CK. 9.  2010. Sympathetic and sensory innervation of brown adipose tissue. Int. J. Obesity 34:Suppl. 1S36–42 [Google Scholar]
  10. Bengtsson T, Cannon B, Nedergaard J. 10.  2000. Differential adrenergic regulation of gene expression of the β-adrenoreceptor subtypes β1, β2, and β3 in brown adipocytes. Biochem. J. 347:643–51 [Google Scholar]
  11. Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O. 11.  2000. Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J. Nutr. 130:122943–48 [Google Scholar]
  12. Brown JM, Boysen MS, Chung S, Fabiyi O, Morrison RF. 12.  et al. 2004. Conjugated linoleic acid induces human adipocyte delipidation: autocrine/paracrine regulation of MEK/ERK signaling by adipocytokines. J. Biol. Chem. 279:26735–47 [Google Scholar]
  13. Brown JM, Halvorsen YD, Lea-Currie YR, Geigerman C, McIntosh M. 13.  2001. 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. 131:92316–21 [Google Scholar]
  14. Brown JM, Sandberg-Boysen M, Jensen SS, Morrison R, Storkson J. 14.  et al. 2003. Isomer-specific regulation of metabolism and PPARγ by CLA in human preadipocytes. J. Lipid Res. 44:1287–300 [Google Scholar]
  15. Cannon B, Nedergaard J. 15.  2004. Brown adipose tissue: function and physiological significance. Physiol. Rev. 84:277–359 [Google Scholar]
  16. Carvalho RF, Uehara SK, Rosa G. 16.  2012. Microencapsulated conjugated linoleic acid associated with hypocaloric diet reduces body fat in sedentary women with metabolic syndrome. Vasc. Health Risk Manag. 8:661–67 [Google Scholar]
  17. Celi FS. 17.  2009. Brown adipose tissue—when it pays to be inefficient. N. Engl. J. Med. 360:151553–56 [Google Scholar]
  18. Chao P, Yang L, Aja S, Moran T, Bi S. 18.  2011. Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity. Cell Metab. 13:5573–83 [Google Scholar]
  19. Chardigny JM, Hasselwander O, Genty M, Kraemer K, Ptock A, Sébédio JL. 19.  2003. Effect of conjugated FA on feed intake, body composition, and liver FA in mice. Lipids 38:9895–902 [Google Scholar]
  20. Chen SC, Lin YH, Huang HP, Hsu WL, Houng JY, Huang CK. 20.  2012. Effect of conjugated linoleic acid supplementation on weight loss and body fat composition in a Chinese population. Nutrition 28:5559–65 [Google Scholar]
  21. Choi SH, Chung KY, Johnson BJ, Go GW, Kim KH. 21.  et al. 2013. Co-culture of bovine muscle satellite cells with preadipocytes increases PPARγ and C/EBPβ gene expression in differentiated myoblasts and increases GPR43 gene expression in adipocytes. J. Nutr. Biochem. 24:3539–43 [Google Scholar]
  22. Chung S, Brown JM, Provo JN, Hopkins R, McIntosh MK. 22.  2005. Conjugated linoleic acid promotes human adipocyte insulin resistance through NFκB-dependent cytokine production. J. Biol. Chem. 280:38445–56 [Google Scholar]
  23. Chung S, Brown JM, Sandberg MB, McIntosh M. 23.  2005. Trans-10,Cis-12 CLA increases adipocyte lipolysis and alters lipid droplet-associated proteins: role of mTor and ERK signaling. J. Lipid Res. 46:885–95 [Google Scholar]
  24. Close RN, Schoeller DA, Watras AC, Nora EH. 24.  2007. Conjugated linoleic acid supplementation alters the 6-mo change in fat oxidation during sleep. Am. J. Clin. Nutr. 86:3797–804 [Google Scholar]
  25. Colakoglu S, Colakoglu M, Taneli F, Cetinoz F, Turkmen M. 25.  2006. Cumulative effects of conjugated linoleic acid and exercise on endurance development, body composition, serum leptin and insulin levels. J. Sports Med. Phys. Fitness 46:4570–77 [Google Scholar]
  26. Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D. 26.  et al. 1992. Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J. Cell Sci. 103:Pt. 4931–42 [Google Scholar]
  27. Cypess AM, Lehman S, Williams G, Tal I, Rodman D. 27.  et al. 2009. Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 360:151509–17 [Google Scholar]
  28. Czauderna M, Kowalczyk J, Korniluk K. 28.  2007. Effect of dietary conjugated linoleic acid and selenized yeast on the concentration of fatty acids and minerals in rats. Arch. Anim. Nutr. 61:2135–50 [Google Scholar]
  29. den Hartigh LJ, Han CY, Wang S, Omer M, Chait A. 29.  2013. 10E,12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species. J. Lipid Res. 54:112964–78 [Google Scholar]
  30. Ealey KN, El-Sohemy A, Archer MC. 30.  2002. Effects of dietary conjugated linoleic acid on the expression of uncoupling proteins in mice and rats. Lipids 37:9853–61 [Google Scholar]
  31. Ebrahimi M, Rajion MA, Goh YM. 31.  2014. Effects of oils rich in linoleic and α-linolenic acids on fatty acid profile and gene expression in goat meat. Nutrients 6:93913–28 [Google Scholar]
  32. Evans M, Lin X, Odle J, McIntosh M. 32.  2002. Trans-10, cis-12 conjugated linoleic acid increases fatty acid oxidation in 3T3-L1 preadipocytes. J. Nutr. 132:3450–55 [Google Scholar]
  33. Feldman H, Golozoubova V, Cannon B, Nedergaard J. 33.  2009. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living in thermoneutrality. Cell Metab. 9:203–9 [Google Scholar]
  34. Fiorentini G, Lage JF, Carvalho IP, Messana JD, Canesin RC. 34.  et al. 2015. Lipid sources with different fatty acid profile alters the fatty acid profile and quality of beef from confined Nellore steers. Asian-Australas. J. Anim. Sci. 28:7976–86 [Google Scholar]
  35. Frontini A, Cinti S. 35.  2010. Distribution and development of brown adipocytes in the murine and human adipose organ. Cell Metab. 11:253–56 [Google Scholar]
  36. Gao Z, Wang F, Xiang X, Cao R, Zhang W, Gao S. 36.  2007. Intracerebroventricular administration of conjugated linoleic acid (CLA) inhibits food intake by decreasing the gene expression of NPY and AgRP. Neurosci. Lett. 418:217–21 [Google Scholar]
  37. Gaullier JM, Halse J, Høivik HO, Høye K, Syvertsen C. 37.  et al. 2007. Six months supplementation with conjugated linoleic acid induces regional-specific fat mass decreases in overweight and obese. Br. J. Nutr. 97:3550–60 [Google Scholar]
  38. Gaullier JM, Halse J, Høye K, Kristiansen K, Fagertun H. 38.  et al. 2004. Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Am. J. Clin. Nutr. 79:61118–25 [Google Scholar]
  39. Gaullier JM, Halse J, Høye K, Kristiansen K, Fagertun H. 39.  et al. 2005. Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans. J. Nutr. 135:4778–84 [Google Scholar]
  40. Ha YL, Grimm NK, Pariza MW. 40.  1987. Anticarcinogens from fried ground beef: heat-altered derivatives of linoleic acid. Carcinogenesis 8:1881–87 [Google Scholar]
  41. Halade GV, Rahman MM, Fernandes G. 41.  2010. Differential effects of conjugated linoleic acid isomers in insulin-resistant female C57bl/6J mice. J. Nutr. Biochem. 21:332–37 [Google Scholar]
  42. Hargrave KM, Li C, Meyer BJ, Kachman SD, Hartzel DL. 42.  et al. 2002. Adipose depletion and apoptosis induced by trans-10, cis-12 conjugated linoleic acid in mice. Obesity Res. 10:1284–90 [Google Scholar]
  43. House RL, Cassady JP, Eisen EJ, Eling TE, Collins JB. 43.  et al. 2005. Functional genomic characterization of delipidation elicited by trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) in a polygenic obese line of mice. Physiol. Genomics 21:351–61 [Google Scholar]
  44. Hsu Y-C, Ip MM. 44.  2011. Conjugated linoleic acid-induced apoptosis in mouse mammary tumor cells is mediated by both G protein coupled receptor-dependent activation of the AMP-activated protein kinase pathway and by oxidative stress. Cell. Signal. 23:2013–20 [Google Scholar]
  45. Hughes PE, Hunter WJ, Tove SB. 45.  1982. Biohydrogenation of unsaturated fatty acids. Purification and properties of cis-9,trans-11-octadecadienoate reductase. J. Biol. Chem. 257:3643–49 [Google Scholar]
  46. Ishibashi J, Seale P. 46.  2010. Beige can be slimming. Science 328:1113–14 [Google Scholar]
  47. Jaudszus A, Moeckel P, Hamelmann E, Jahreis G. 47.  2010. Trans-10, Cis-12-CLA-caused lipodystrophy is associated with profound changes of fatty acid profiles of liver, white adipose tissue and erythrocytes in mice: possible link to tissue-specific alterations of fatty acid desaturation. Ann. Nutr. Metab. 57:103–11 [Google Scholar]
  48. Jiao P, Feng B, Ma J, Nie Y, Paul E, Li Y. 48.  et al. 2012. Constitutive activation of IKKβ in adipose tissue prevents diet-induced obesity in mice. Endocrinology 153:1154–65 [Google Scholar]
  49. Jørgensen H, Hansen CH, Mu H, Jakobsen K. 49.  2010. Protein and energy metabolism of young male Wistar rats fed conjugated linoleic acid as structured triacylglycerol. Arch. Anim. Nutr. 64:4322–36 [Google Scholar]
  50. Kang K, Liu W, Albright KJ, Park Y, Pariza MW. 50.  2003. Trans-10,cis-12 CLA inhibits differentiation of 3T3-L1 adipocytes and decreases PPAR gamma expression. Biochem. Biophys. Res. Commun. 303:3795–99 [Google Scholar]
  51. Kennedy A, Chung S, Lapoint K, Fabiyi O, McIntosh MK. 51.  2008. Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARγ activity in primary cultures of human adipocytes. J. Nutr. 138:455–61 [Google Scholar]
  52. Kennedy A, Martinez K, Chung S, LaPoint K, Hopkins R. 52.  et al. 2010. Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes. J. Lipid Res. 51:1906–17 [Google Scholar]
  53. Kennedy A, Martinez K, Schmidt S, Mandrup S, LaPoint K, McIntosh M. 53.  2010. Antiobesity mechanisms of action of conjugated linoleic acid. J. Nutr. Biochem. 21:3171–79 [Google Scholar]
  54. Kennedy A, Overman A, Lapoint K, Hopkins R, West T. 54.  et al. 2009. Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol. J. Lipid Res. 50:225–32 [Google Scholar]
  55. Kepler CR, Hirons KP, McNeill JJ, Tove SB. 55.  1966. Intermediates and products of the biohydrogenation of linoleic acid by Butyrivibrio fibrisolvens. J. Biol. Chem. 241:1350–54 [Google Scholar]
  56. Kim YJ, Liu RH, Bond DR, Russell JB. 56.  2000. Effect of linoleic acid concentration on conjugated linoleic acid production by Butyrivibrio fibriosolvens A38. Appl. Environm. Microbiol. 66:5226–30 [Google Scholar]
  57. Kim YJ, Liu RH, Rychlik JL, Russell JB. 57.  2002. The enrichment of a ruminal bacterium (Megasphaera elsdenii YJ-4) that produces the trans-10, cis-12 isomer of conjugated linoleic acid. J. Appl. Microbiol. 92:976–82 [Google Scholar]
  58. Kishino S, Ogawa J, Ando A, Omura Y, Shimizu S. 58.  2002. Ricinoleic acid and castor oil as substrates for conjugated linoleic acid production by washed cells of Lactobacillus plantarum. Biosci. Biotechnol. Biochem. 66:102283–86 [Google Scholar]
  59. Kramer JKG, Cruz-Hernandez C, Deng Z, Zhou J, Jahreis G, Dugan MER. 59.  2004. Analysis of conjugated linoleic acid and trans 18:1 isomers in synthetic and animal products. Am. J. Clin. Nutr. 79:6 Suppl.1137S–45 [Google Scholar]
  60. Langin D. 60.  2010. Recruitment of brown fat and conversion of white into brown adipocytes: strategies to fight the metabolic complications of obesity?. Biochim. Biophys. Acta 1801:372–76 [Google Scholar]
  61. LaRosa PC, Miner J, Xia Y, Zhou Y, Kachman S, Fromm ME. 61.  2006. Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis. Physiol. Genom. 27:282–94 [Google Scholar]
  62. LaRosa PC, Riethoven JJ, Chen H, Xia Y, Zhou Y. 62.  et al. 2007. Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes. Physiol. Genomics 31:544–53 [Google Scholar]
  63. Laso N, Brugué E, Vidal J, Ros E, Arnaiz JA. 63.  et al. 2007. Effects of milk supplementation with conjugated linoleic acid (isomers cis-9, trans-11 and trans-10, cis-12) on body composition and metabolic syndrome components. Br. J. Nutr. 98:4860–67 [Google Scholar]
  64. Liu LF, Purushotham A, Wendel AA, Belury MA. 64.  2007. 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. 292:6G1671–82 [Google Scholar]
  65. López-Plaza B, Bermejo LM, Koester Weber T, Parra P, Serra F. 65.  et al. 2013. Effects of milk supplementation with conjugated linoleic acid on weight control and body composition in healthy overweight people. Nutr. Hosp. 28:62090–98 [Google Scholar]
  66. MacRedmond R, Singhera G, Attridge S, Bahzad M, Fava C. 66.  et al. 2010. Conjugated linoleic acid improves airway hyper-reactivity in overweight mild asthmatics. Clin. Exp. Allergy 40:71071–78 [Google Scholar]
  67. Madsen L, Pedersen LM, Lillefosse HH, Fjaere E, Bronstad I. 67.  et al. 2010. UCP1 induction during recruitment of brown adipocytes in white adipose tissue is dependent on cyclooxygenase activity. PLOS ONE 5:6e11391 [Google Scholar]
  68. Martin JC, Grégoire S, Siess MH, Genty M, Chardigny JM. 68.  et al. 2000. Effects of conjugated linoleic acid isomers on lipid-metabolizing enzymes in male rats. Lipids 35:91–98 [Google Scholar]
  69. Martinez KB, Kennedy AJ, McIntosh MK. 69.  2010. Conjugated linoleic acid. Encyclopedia of Dietary Supplements P Coates, JM Betz, MR Blackman, GM Cragg, M Levine, et al. 166–74 New York: Informa Healthc, 2nd ed.. [Google Scholar]
  70. Martinez K, Kennedy A, McIntosh M. 70.  2011. JNK inhibition by SP600125 attenuates trans-10, cis-12 conjugated linoleic acid-mediated regulation of inflammation and lipogenic gene expression. Lipids 46:885–92 [Google Scholar]
  71. Martinez K, Shyamasundar S, Kennedy A, Chuang CC, Marsh A. 71.  et al. 2013. Diacylglycerol kinase inhibitor R59022 attenuates conjugated linoleic acid-mediated inflammation in human adipocytes. J. Lipid Res. 54:662–70 [Google Scholar]
  72. Martins SV, Lopes PA, Alfaia CM, Rodrigues PO, Alves SP. 72.  et al. 2010. Serum adipokine profile and fatty acid composition of adipose tissues are affected by conjugated linoleic acid and saturated fat diets in obese Zucker rats. Br. J. Nutr. 103:6869–78 [Google Scholar]
  73. Mattsson CL, Csikasz RI, Chernogubova E, Yamamoto DL, Hogberg HT. 73.  et al. 2011. β1-adrenergic receptors increase UCP1 in human MADS brown adipocytes and rescue cold-acclimated β3-adrenergic receptor-knockout mice via nonshivering thermogenesis. Am. J. Physiol. Endocrinol. Metab. 301:6E1108–18 [Google Scholar]
  74. McCrorie TA, Keaveney EM, Wallace JM, Binns N, Livingstone MB. 74.  2011. Human health effects of conjugated linoleic acid from milk and supplements. Nutr. Res. Rev. 24:2206–27 [Google Scholar]
  75. Metges CC, Lehmann L, Boeuf S, Petzke KJ, Müller A. 75.  et al. 2003. cis-9,trans-11 and trans-10,cis-12 CLA affect lipid metabolism differently in primary white and brown adipocytes of Djungarian hamsters. Lipids 38:111133–42 [Google Scholar]
  76. Milligan G, Ulven T, Murdoch H, Hudson BD. 76.  2014. G-protein-coupled receptors for free fatty acids: nutritional and therapeutic targets. Br. J. Nutr. 111:Suppl. 1S3–7 [Google Scholar]
  77. Miner JL, Cederberg CA, Nielsen MK, Chen X, Baile CA. 77.  2001. Conjugated linoleic acid (CLA), body fat, and apoptosis. Obes. Res. 9:2129–34 [Google Scholar]
  78. Mitchell P, McLeod R. 78.  2008. Conjugated linoleic acid and atherosclerosis: studies in animal models. Biochem. Cell Biol. 86:4293–301 [Google Scholar]
  79. Morsy TA, Kholif SM, Kholif AE, Matloup OH, Salem AZ, Elella AA. 79.  2015. Influence of sunflower whole seeds or oil on ruminal fermentation, milk production, composition, and fatty acid profile in lactating goats. Asian-Australas J. Anim. Sci. 28:81116–22 [Google Scholar]
  80. Mougios V, Matsakas A, Petridou A, Ring S, Sagredos A. 80.  et al. 2001. Effect of supplementation with conjugated linoleic acid on human serum lipids and body fat. J. Nutr. Biochem. 12:10585–94 [Google Scholar]
  81. Murphy KT, Schwartz GJ, Nguyen NL, Mendez JM, Ryu V, Bartness TJ. 81.  2013. Leptin-sensitive sensory nerves innervate white fat. Am. J. Physiol. Endocrin. Metab. 304:E1338–47 [Google Scholar]
  82. Nagao K, Wang Y-M, Inoue N, Han S-Y, Buang Y. 82.  et al. 2003. The 10trans, 12cis isomer of conjugated linoleic acid promotes energy metabolism in OLETF rats. Nutrition 19:652–56 [Google Scholar]
  83. Nazare JA, de la Perrière AB, Bonnet F, Desage M, Peyrat J. 83.  et al. 2007. Daily intake of conjugated linoleic acid-enriched yoghurts: effects on energy metabolism and adipose tissue gene expression in healthy subjects. Br. J. Nutr. 97:2273–80 [Google Scholar]
  84. Norris LE, Collene AL, Asp ML, Hsu JC, Liu LF. 84.  et al. 2009. Comparison of dietary conjugated linoleic acid with safflower oil on body composition in obese postmenopausal women with type 2 diabetes mellitus. Am. J. Clin. Nutr. 90:3468–76 [Google Scholar]
  85. Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J. 85.  et al. 2011. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 480:104–8 [Google Scholar]
  86. Obsen T, Faergeman NJ, Chung S, Martinez K, Gobern S. 86.  et al. 2012. Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes. J. Nutr. Biochem. 23:6580–90 [Google Scholar]
  87. Oh DY, Lagakos WS. 87.  2011. The role of G-protein-coupled receptors in mediating the effect of fatty acids on inflammation and insulin sensitivity. Curr. Opin. Clin. Nutr. Metab. Care 14:4322–27 [Google Scholar]
  88. Parra P, Serra F, Palou A. 88.  2010. Moderate doses of conjugated linoleic acid isomers mix contribute to lowering body fat content maintaining insulin sensitivity and a noninflammatory pattern in adipose tissue in mice. J. Nutr. Biochem. 21:107–15 [Google Scholar]
  89. Peters JM, Park Y, Gonzalez FJ, Pariza MW. 89.  2001. Influence of conjugated linoleic acid on body composition and target gene expression in peroxisome proliferator-activated receptor alpha-null mice. Biochim. Biophys. Acta 1533:3233–42 [Google Scholar]
  90. Pfeuffer M, Fielitz K, Laue C, Winkler P, Rubin D. 90.  et al. 2011. CLA does not impair endothelial function and decreases body weight as compared with safflower oil in overweight and obese male subjects. J. Am. Coll. Nutr. 30:119–28 [Google Scholar]
  91. Pini M, Touch S, Poirier H, Dalmas E, Niot I. 91.  et al. 2016. Adipose tissue adaptive response to trans-10, cis-12-conjugated linoleic acid engages alternatively activated M2 macrophages. FASEB J 30:241–51 [Google Scholar]
  92. Pinkoski C, Chilibeck PD, Candow DG, Esliger D, Ewaschuk JB. 92.  et al. 2006. The effects of conjugated linoleic acid supplementation during resistance training. Med. Sci. Sports Exerc. 38:2339–48 [Google Scholar]
  93. Poirier H, Niot I, Clement L, Guerre-Millo M, Besnard P. 93.  2005. Development of conjugated linoleic acid (CLA)-mediated lipoatrophic syndrome in the mouse. Biochimie 87:73–79 [Google Scholar]
  94. Poirier H, Shapiro J, Kim R, Lazar M. 94.  2006. Nutritional supplementation with trans-10, cis-12 conjugated linoleic acid induces inflammation of white adipose tissue. Diabetes 55:1634–41 [Google Scholar]
  95. Qiu Y, Nguyen KD, Odegaard JI, Cui X, Tian X. 95.  et al. 2014. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157:61292–308 [Google Scholar]
  96. Racine NM, Watras AC, Carrel AL, Allen DB, McVean JJ. 96.  et al. 2010. Effect of conjugated linoleic acid on body fat accretion in overweight or obese children. Am. J. Clin. Nutr. 91:51157–64 [Google Scholar]
  97. Raff M, Tholstrup T, Basu S, Nonboe P, Sørensen MT, Straarup EM. 97.  2008. 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. 138:3509–14 [Google Scholar]
  98. Raff M, Tholstrup T, Toubro S, Bruun JM, Lund P. 98.  et al. 2009. Conjugated linoleic acids reduce body fat in healthy postmenopausal women. J. Nutr. 139:71347–52 [Google Scholar]
  99. Rahman SM, Wang Y, Yotsumoto H, Cha J, Han S. 99.  et al. 2001. Effects of conjugated linoleic acid on serum leptin concentration, body-fat accumulation, and beta-oxidation of fatty acid in OLETF rats. Nutrition 17:5385–90 [Google Scholar]
  100. Reardon M, Gobern S, Martinez K, Shen W, Reid T, McIntosh M. 100.  2012. Oleic acid attenuates trans-10, cis-12 conjugated linoleic acid-mediated inflammatory gene expression in human adipocytes. Lipids 47:111043–51 [Google Scholar]
  101. Risérus U, Arner P, Brismar K, Vessby B. 101.  2002. Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care 25:1516–21 [Google Scholar]
  102. Risérus U, Basu S, Jovinge S, Fredrikson GN, Arnlöv J, Vessby B. 102.  2002. 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 106:151925–29 [Google Scholar]
  103. Risérus U, Berglund L, Vessby B. 103.  2001. Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial. Int. J. Obes. Relat. Metab. Disord. 25:81129–35 [Google Scholar]
  104. Risérus U, Vessby B, Arnlöv J, Basu S. 104.  2004. Effects of cis-9, trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men. Am. J. Clin. Nutr. 80:2279–83 [Google Scholar]
  105. Rodríguez E, Ribot J, Palou A. 105.  2002. Trans-10, cis-12, but not cis-9, trans-11 CLA isomer, inhibits brown adipocyte thermogenic capacity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282:6R1789–97 [Google Scholar]
  106. Sartorius T, Drescher A, Panse M, Lastovicka P, Peter A. 106.  et al. 2015. Mice lacking free fatty acid receptor 1 (GPR40/FFAR1) are protected against conjugated linoleic acid-induced fatty liver but develop inflammation and insulin resistance in the brain. Cell Physiol. Biochem. 35:62272–84 [Google Scholar]
  107. Sauer LA, Dauchy RT, Blask DE, Krause JA, Davidson LK. 107.  et al. 2004. Conjugated linoleic acid isomers and trans fatty acids inhibit fatty acid transport in hepatoma 7288CTC and inguinal fat pads in Buffalo rats. J. Nutr. 134:81989–97 [Google Scholar]
  108. Schmidt J, Liebscher K, Merten N, Grundmann M, Mielenz M. 108.  et al. 2011. Conjugated linoleic acids mediate insulin release through islet G protein-coupled receptor FFA1/GPR40. J. Biol. Chem. 286:1411890–94 [Google Scholar]
  109. Seale P, Kajimura S, Spiegelman BM. 109.  2009. Transcriptional control of brown adipocyte development and physiological function—of mice and men. Genes Dev. 23:7788–97 [Google Scholar]
  110. Sébédio JL, Angioni E, Chardigny JM, Grégoire S, Juanéda P, Berdeaux O. 110.  2001. The effect of conjugated linoleic acid isomers on fatty acid profiles of liver and adipose tissues and their conversion to isomers of 16:2 and 18:3 conjugated fatty acids in rats. Lipids 36:6575–82 [Google Scholar]
  111. Shen W, Baldwin J, Collins B, Hixson L, Lee KT. 111.  et al. 2015. Low level of trans-10, cis-12 conjugated linoleic acid decreases adiposity and increases browning independent of inflammatory signaling in overweight Sv129 mice. J. Nutr. Biochem. 26:616–25 [Google Scholar]
  112. Shen W, Chuang CC, Martinez K, Reid T, Brown JM. 112.  et al. 2013. Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice. J. Lipid Res. 54:4909–22 [Google Scholar]
  113. Shen W, Martinez K, Chuang CC, McIntosh M. 113.  2013. The phospholipase C (PLC) inhibitor U73122 attenuates trans-10, cis-12 conjugated linoleic acid-mediated inflammatory signaling and insulin resistance in human adipocytes. J. Nutr. 243:584–90 [Google Scholar]
  114. Shivani S, Srivastava A, Shandilya UK, Kale V, Tyagi AK. 114.  2016. Dietary supplementation of Butyrivibrio fibrisolvens alters fatty acids of milk and rumen fluid in lactating goats. J. Sci. Food Agric. 96:1716–22 [Google Scholar]
  115. Smedman A, Basu S, Jovinge S, Fredrikson GN, Vessby B. 115.  2005. Conjugated linoleic acid increased C-reactive protein in human subjects. Br. J. Nutr. 94:5791–95 [Google Scholar]
  116. Smedman A, Vessby B. 116.  2001. Conjugated linoleic acid supplementation in humans—metabolic effects. Lipids 36:8773–81 [Google Scholar]
  117. Steck SE, Chalecki AM, Miller P, Conway J, Austin GL. 117.  et al. 2007. Conjugated linoleic acid supplementation for twelve weeks increases lean body mass in obese humans. J. Nutr. 137:51188–93 [Google Scholar]
  118. Stout MB. 118.  2011. Differential metabolic effects in white and brown adipose tissue by conjugated linoleic acid elicit lipodystrophy-associated hepatic insulin resistance PhD Diss., Ohio State Univ., Columbus [Google Scholar]
  119. Stout MB, Wendel AA, Asp ML, Tian M, Cole RM. 119.  et al. 2010. Dietary conjugated linoleic acid alters adipose phenotype in a depot-specific manner in mice Presented at Keystone Symp. Mol. Cell. Biol., Jan. 24–29, Keystone, Colo. [Google Scholar]
  120. Subbaiah PV, Sircar D, Aizezi B, Mintzer E. 120.  2010. Differential effects of conjugated linoleic acid isomers on the biophysical and biochemical properties of model membranes. Biochim. Biophys. Acta 1798:3506–14 [Google Scholar]
  121. Syvertsen C, Halse J, Høivik HO, Gaullier JM, Nurminiemi M. 121.  et al. 2007. The effect of 6 months supplementation with conjugated linoleic acid on insulin resistance in overweight and obese. Int. J. Obes. 31:71148–54 [Google Scholar]
  122. Tang T, Zhang J, Yin J, Staszkiewicz J, Gawronska-Kozak B. 122.  et al. 2010. Uncoupling of inflammation and insulin resistance by NF-kappaB in transgenic mice through elevated energy expenditure. J. Biol. Chem. 285:74637–44 [Google Scholar]
  123. Tholstrup T, Raff M, Straarup E, Lund P, Basu S, Bruun JM. 123.  2008. An oil mixture with trans-10, cis-12 conjugated linoleic acid increases markers of inflammation and in vivo lipid peroxidation compared with cis-9, trans-11 conjugated linoleic acid in postmenopausal women. J. Nutr. 138:1445–51 [Google Scholar]
  124. Thom E, Wadstein J, Gudmundsen O. 124.  2001. Conjugated linoleic acid reduces body fat in healthy exercising humans. J. Int. Med. Res. 29:5392–96 [Google Scholar]
  125. Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T. 125.  et al. 2000. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes 49:1534–42 [Google Scholar]
  126. Vaughan CH, Zarebidaki E, Ehlen JC, Bartness TJ. 126.  2014. Analysis and measurement of the sympathetic and sensory innervation of white and brown adipose tissue. Methods Enzymol. 537:199–225 [Google Scholar]
  127. Vegiopoulos A, Müller-Decker K, Strzoda D, Schmitt I, Chichelnitskiy E. 127.  et al. 2010. Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 328:1158–61 [Google Scholar]
  128. Viladomiu M, Hontecillas R, Bassaganya-Riera J. 128.  2016. Modulation of inflammation and immunity by dietary conjugated linoleic acid. Eur. J. Pharmacol. doi: 10.1016/j.ejphar.2015.03.095. In press [Google Scholar]
  129. Wallace RJ, McKain N, Shingfield KJ, Devillard E. 129.  2007. Isomers of conjugated linoleic acids are synthesized via different mechanisms in ruminal digesta and bacteria. J. Lipid Res. 48:102247–54 [Google Scholar]
  130. Wang Y, Proctor SD. 130.  2013. Current issues surrounding the definition of trans-fatty acids: implications for health, industry and food labels. Br. J. Nutr. 110:81369–83 [Google Scholar]
  131. Watras AC, Buchholz AC, Close RN, Zhang Z, Schoeller DA. 131.  2007. The role of conjugated linoleic acid in reducing body fat and preventing holiday weight gain. Int. J. Obes. 31:3481–87 [Google Scholar]
  132. Wendel AA, Purushotham A, Liu LF, Belury MA. 132.  2009. Conjugated linoleic acid induces uncoupling protein 1 in white adipose tissue of ob/ob mice. Lipids 44:975–82 [Google Scholar]
  133. West DB, Blohm FY, Truett AA, DeLany JP. 133.  2000. Conjugated linoleic acid persistently increases total energy expenditure in AKR/J mice without increasing uncoupling protein gene expression. J. Nutr. 130:102471–77 [Google Scholar]
  134. Whigham LD, Watras AC, Schoeller DA. 134.  2007. Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. Am. J. Clin. Nutr. 85:1203–11 [Google Scholar]
  135. Ye L, Wu J, Cohen P, Kazak L, Khandekar M. 135.  et al. 2013. Fat cells directly sense temperature to activate thermogenesis. PNAS 110:3012480–85 [Google Scholar]
  136. Youngstrom T, Bartness T. 136.  1998. White adipose tissue sympathetic nervous system denervation increases fat pad mass and fat cell number. Am. J. Physiol. 275:R1488–93 [Google Scholar]
  137. Yuan G-F, Sinclair AJ, Sun H-Y, Li D. 137.  2009. Fatty acid composition in tissues of mice fed diets containing conjugated linolenic acid and conjugated linoleic acid. J. Food Lipids 16:148–63 [Google Scholar]
  138. Zhao WS, Zhai JJ, Wang YH, Xie PS, Yin XJ. 138.  et al. 2009. Conjugated linoleic acid supplementation enhances antihypertensive effect of ramipril in Chinese patients with obesity-related hypertension. Am. J. Hypertens. 22:6680–86 [Google Scholar]
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