Table of Contents Author Guidelines Submit a Manuscript
Journal of Nutrition and Metabolism
Volume 2012 (2012), Article ID 932928, 13 pages
http://dx.doi.org/10.1155/2012/932928
Review Article

Dietary Conjugated Linoleic Acid and Hepatic Steatosis: Species-Specific Effects on Liver and Adipose Lipid Metabolism and Gene Expression

1Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA
2Department of Animal and Veterinary Sciences, Clemson University, Clemson, SC 29634, USA

Received 15 May 2011; Accepted 22 June 2011

Academic Editor: Konstantinos Kantartzis

Copyright © 2012 Diwakar Vyas et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Salas-Salvadó, F. Márquez-Sandoval, and M. Bulló, “Conjugated Linoleic acid intake in humans: a systematic review focusing on its effect on body composition, glucose, and lipid metabolism,” Critical Reviews in Food Science and Nutrition, vol. 46, no. 6, pp. 479–488, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. K. M. Flegal, M. D. Carroll, C. L. Ogden, and L. R. Curtin, “Prevalence and trends in obesity among US adults, 1999-2008,” Journal of the American Medical Association, vol. 303, no. 3, pp. 235–241, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. C. L. Ogden, M. D. Carroll, L. R. Curtin, M. M. Lamb, and K. M. Flegal, “Prevalence of high body mass index in US children and adolescents, 2007-2008,” Journal of the American Medical Association, vol. 303, no. 3, pp. 242–249, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. A. M. Zivkovic, J. B. German, and A. J. Sanyal, “Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease,” American Journal of Clinical Nutrition, vol. 86, no. 2, pp. 285–300, 2007. View at Google Scholar · View at Scopus
  5. E. Fabbrini, S. Sullivan, and S. Klein, “Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications,” Hepatology, vol. 51, no. 2, pp. 679–689, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. A. J. McCullough, “The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease,” Clinics in Liver Disease, vol. 8, no. 3, pp. 521–533, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. J. K. Reddy and M. S. Rao, “Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation,” American Journal of Physiology, vol. 290, no. 5, pp. G852–G858, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. F. Diraison, P. H. Moulin, and M. Beylot, “Contribution of hepatic de novo lipogenesis and reesterification of plasma non esterified fatty acids to plasma triglyceride synthesis during non-alcoholic fatty liver disease,” Diabetes and Metabolism, vol. 29, no. 5, pp. 478–485, 2003. View at Google Scholar · View at Scopus
  9. M. J. Ronis, Y. Chen, C. H. Jo, P. Simpson, and T. M. Badger, “Diets containing soy protein isolate increase hepatic CYP3A expression and inducibility in weanling male rats exposed during early development,” Journal of Nutrition, vol. 134, no. 12, pp. 3270–3276, 2004. View at Google Scholar · View at Scopus
  10. M. Charlton, R. Sreekumar, D. Rasmussen, K. Lindor, and K. S. Nair, “Apolipoprotein synthesis in nonalcoholic steatohepatitis,” Hepatology, vol. 35, no. 4, pp. 898–904, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. H. L. Huang, W. Y. Lin, L. T. Lee, H. H. Wang, W. J. Lee, and K. C. Huang, “Metabolic syndrome is related to nonalcoholic steatohepatitis in severely obese subjects,” Obesity Surgery, vol. 17, no. 11, pp. 1457–1463, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. Z. Z. Li, M. Berk, T. M. McIntyre, and A. E. Feldstein, “Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-Coa desaturase,” Journal of Biological Chemistry, vol. 284, no. 9, pp. 5637–5644, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. C. P. Day and O. F. W. James, “Steatohepatitis: a tale of two ‘Hits’,” Gastroenterology, vol. 114, no. 4 I, pp. 842–845, 1998. View at Publisher · View at Google Scholar · View at Scopus
  14. Y. Park and M. W. Pariza, “Mechanisms of body fat modulation by conjugated linoleic acid (CLA),” Food Research International, vol. 40, no. 3, pp. 311–323, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. M. W. Pariza, Y. Park, and M. E. Cook, “The biologically active isomers of conjugated linoleic acid,” Progress in Lipid Research, vol. 40, no. 4, pp. 283–298, 2001. View at Publisher · View at Google Scholar · View at Scopus
  16. K. Eulitz, M. P. Yurawecz, N. Sehat et al., “Preparation, separation, and confirmation of the eight geometrical cis/trans conjugated linoleic acid isomers 8, 10- through 11, 13-18:2,” Lipids, vol. 34, no. 8, pp. 873–877, 1999. View at Publisher · View at Google Scholar · View at Scopus
  17. N. Sehat, R. Rickert, M. M. Mossoba et al., “Improved separation of conjugated fatty acid methyl esters by silver ion-high-performance liquid chromatography,” Lipids, vol. 34, no. 4, pp. 407–413, 1999. View at Publisher · View at Google Scholar · View at Scopus
  18. P. W. Parodi, “Conjugated octadecadienoic acids of milk-fat,” Journal of Dairy Science, vol. 60, no. 10, pp. 1550–1553, 1977. View at Google Scholar
  19. S. F. Chin, W. Liu, J. M. Storkson, Y. L. Ha, and M. W. Pariza, “Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognized class of anticarcinogens,” Journal of Food Composition and Analysis, vol. 5, no. 3, pp. 185–197, 1992. View at Google Scholar · View at Scopus
  20. K. N. Lee, D. Kritchevsky, and M. W. Parizaa, “Conjugated linoleic acid and atherosclerosis in rabbits,” Atherosclerosis, vol. 108, no. 1, pp. 19–25, 1994. View at Publisher · View at Google Scholar · View at Scopus
  21. C. C. Miller, Y. Park, M. W. Pariza, and M. E. Cook, “Feeding conjugated linoleic acid to animals partially overcomes catabolic responses due to endotoxin injection,” Biochemical and Biophysical Research Communications, vol. 198, no. 3, pp. 1107–1112, 1994. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. Y. Park, K. J. Albright, W. Liu, J. M. Storkson, M. E. Cook, and M. W. Pariza, “Effect of conjugated linoleic acid on body composition in mice,” Lipids, vol. 32, no. 8, pp. 853–858, 1997. View at Publisher · View at Google Scholar · View at Scopus
  23. C. Ip, Y. Dong, M. M. Ip et al., “Conjugated linoleic acid isomers and mammary cancer prevention,” Nutrition and Cancer, vol. 43, no. 1, pp. 52–58, 2002. View at Google Scholar · View at Scopus
  24. M. A. Belury, “Inhibition of carcinogenesis by conjugated linoleic acid: potential mechanisms of action,” Journal of Nutrition, vol. 132, no. 10, pp. 2995–2998, 2002. View at Google Scholar · View at Scopus
  25. Y. Park, J. M. Storkson, K. J. Albright, W. Liu, and M. W. Pariza, “Evidence that the trans-10,cis-12 isomer of conjugated linoleic acid induces body composition changes in mice,” Lipids, vol. 34, no. 3, pp. 235–241, 1999. View at Google Scholar · View at Scopus
  26. T. M. Larsen, S. Toubro, and A. Astrup, “Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies,” Journal of Lipid Research, vol. 44, no. 12, pp. 2234–2241, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. T. Ide, “Interaction of fish oil and conjugated linoleic acid in affecting hepatic activity of lipogenic enzymes and gene expression in liver and adipose tissue,” Diabetes, vol. 54, no. 2, pp. 412–423, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. M. F. Andreoli, M. A. Gonzalez, M. I. Martinelli, N. O. Mocchiutti, and C. A. Bernal, “Effects of dietary conjugated linoleic acid at high-fat levels on triacylglycerol regulation in mice,” Nutrition, vol. 25, no. 4, pp. 445–452, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. A. K. G. Kadegowda, E. E. Connor, B. B. Teter et al., “Dietary trans fatty acid isomers differ in their effects on mammary lipid metabolism as well as lipogenic gene expression in lactating mice,” Journal of Nutrition, vol. 140, no. 5, pp. 919–924, 2010. View at Publisher · View at Google Scholar · View at PubMed
  30. L. Clément, H. Poirier, I. Niot et al., “Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse,” Journal of Lipid Research, vol. 43, no. 9, pp. 1400–1409, 2002. View at Publisher · View at Google Scholar
  31. P. Degrace, L. Demizieux, J. Gresti, J. M. Chardigny, J. L. Sébédio, and P. Clouet, “Association of liver steatosis with lipid oversecretion and hypotriglyceridaemia in C57BL/6j mice fed trans-10,cis-12-linoleic acid,” FEBS Letters, vol. 546, no. 2-3, pp. 335–339, 2003. View at Publisher · View at Google Scholar
  32. R. Rasooly, D. S. Kelley, J. Greg, and B. E. Mackey, “Dietary trans 10, cis 12-conjugated linoleic acid reduces the expression of fatty acid oxidation and drug detoxification enzymes in mouse liver,” British Journal of Nutrition, vol. 97, no. 1, pp. 58–66, 2007. View at Publisher · View at Google Scholar · View at PubMed
  33. T. Jourdan, L. Djaouti, L. Demizieux, J. Gresti, B. Vergès, and P. Degrace, “Liver carbohydrate and lipid metabolism of insulin-deficient mice is altered by trans-10, cis-12 conjugated linoleic acid,” Journal of Nutrition, vol. 139, no. 10, pp. 1901–1907, 2009. View at Publisher · View at Google Scholar · View at PubMed
  34. Y. Takahashi, M. Kushiro, K. Shinohara, and T. Ide, “Activity and mRNA levels of enzymes involved in hepatic fatty acid synthesis and oxidation in mice fed conjugated linoleic acid,” Biochimica et Biophysica Acta, vol. 1631, no. 3, pp. 265–273, 2003. View at Publisher · View at Google Scholar
  35. L. F. Liu, A. Purushotham, A. A. Wendel, and M. A. Belury, “Combined effects of rosiglitazone and conjugated linoleic acid on adiposity, insulin sensitivity, and hepatic steatosis in high-fat-fed mice,” American Journal of Physiology, vol. 292, no. 6, pp. G1671–G1682, 2007. View at Publisher · View at Google Scholar · View at PubMed
  36. P. Degrace, L. Demizieux, J. Gresti, J. M. Chardigny, J. L. Sébédio, and P. Clouet, “Hepatic steatosis is not due to impaired fatty acid oxidation capacities in C57BL/6J mice fed the conjugated trans-10,cis-12-Isomer of Linoleic Acid,” Journal of Nutrition, vol. 134, no. 4, pp. 861–867, 2004. View at Google Scholar
  37. M. A. Belury and A. Kempa-Steczko, “Conjugated linoleic acid modulates hepatic lipid composition in mice,” Lipids, vol. 32, no. 2, pp. 199–204, 1997. View at Publisher · View at Google Scholar
  38. D. S. Kelley, M. Vemuri, Y. Adkins, S. H. S. Gill, D. Fedor, and B. E. Mackey, “Flaxseed oil prevents trans-10, cis-12-conjugated linoleic acid-induced insulin resistance in mice,” British Journal of Nutrition, vol. 101, no. 5, pp. 701–708, 2009. View at Publisher · View at Google Scholar · View at PubMed
  39. H. Poirier, C. Rouault, L. Clément et al., “Hyperinsulinaemia triggered by dietary conjugated linoleic acid is associated with a decrease in leptin and adiponectin plasma levels and pancreatic beta cell hyperplasia in the mouse,” Diabetologia, vol. 48, no. 6, pp. 1059–1065, 2005. View at Publisher · View at Google Scholar · View at PubMed
  40. N. Tsuboyama-Kasaoka, M. Takahashi, K. Tanemura et al., “Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice,” Diabetes, vol. 49, no. 9, pp. 1534–1542, 2000. View at Google Scholar
  41. H. Poirier, J. S. Shapiro, R. J. Kim, and M. A. Lazar, “Nutritional supplementation with trans-10, cis-12-conjugated linoleic acid induces inflammation of white adipose tissue,” Diabetes, vol. 55, no. 6, pp. 1634–1641, 2006. View at Publisher · View at Google Scholar · View at PubMed
  42. G. V. Halade, M. M. Rahman, and G. Fernandes, “Differential effects of conjugated linoleic acid isomers in insulin-resistant female C57Bl/6J mice,” Journal of Nutritional Biochemistry, vol. 21, no. 4, pp. 332–337, 2010. View at Publisher · View at Google Scholar · View at PubMed
  43. G. V. Halade, M. M. Rahman, and G. Fernandes, “Effect of CLA isomers and their mixture on aging C57Bl/6J mice,” European Journal of Nutrition, vol. 48, no. 7, pp. 409–418, 2009. View at Publisher · View at Google Scholar · View at PubMed
  44. T. Nakanishi, D. Oikawa, T. Koutoku et al., “γ-linolenic acid prevents conjugated linoleic acid-induced fatty liver in mice,” Nutrition, vol. 20, no. 4, pp. 390–393, 2004. View at Publisher · View at Google Scholar · View at PubMed
  45. T. Yanagita, Y. M. Wang, K. Nagao, Y. Ujino, and N. Inoue, “Conjugated linoleic acid-induced fatty liver can be attenuated by combination with docosahexaenoic acid in C57BL/6N mice,” Journal of Agricultural and Food Chemistry, vol. 53, no. 24, pp. 9629–9633, 2005. View at Publisher · View at Google Scholar · View at PubMed
  46. Y. Park, K. J. Albright, J. M. Storkson, W. Liu, M. E. Cook, and M. W. Pariza, “Changes in body composition in mice during feeding and withdrawal of conjugated linoleic acid,” Lipids, vol. 34, no. 3, pp. 243–248, 1999. View at Google Scholar
  47. J. P. DeLany and D. B. West, “Changes in body composition with conjugated linoleic acid,” Journal of the American College of Nutrition, vol. 19, no. 4, pp. 487S–493S, 2000. View at Google Scholar
  48. M. R. Foote, S. L. Giesy, G. Bernal-Santos, D. E. Bauman, and Y. R. Boisclair, “t10,c12-CLA decreases adiposity in peripubertal mice without dose-related detrimental effects on mammary development, inflammation status, and metabolism,” American Journal of Physiology, vol. 299, no. 6, pp. R1521–R1528, 2010. View at Publisher · View at Google Scholar · View at PubMed
  49. A. Purushotham, G. E. Shrode, A. A. Wendel, L. F. Liu, and M. A. Belury, “Conjugated linoleic acid does not reduce body fat but decreases hepatic steatosis in adult Wistar rats,” Journal of Nutritional Biochemistry, vol. 18, no. 10, pp. 676–684, 2007. View at Publisher · View at Google Scholar · View at PubMed
  50. S. Y. Moya-Camarena, J. P. Vanden Heuvel, and M. A. Belury, “Conjugated linoleic acid activates peroxisome proliferator-activated receptor α and β subtypes but does not induce hepatic peroxisome proliferation in Sprague-Dawley rats,” Biochimica et Biophysica Acta, vol. 1436, no. 3, pp. 331–342, 1999. View at Publisher · View at Google Scholar
  51. J. S. Choi, M. H. Jung, H. S. Park, and J. Song, “Effect of conjugated linoleic acid isomers on insulin resistance and mRNA levels of genes regulating energy metabolism in high-fat-fed rats,” Nutrition, vol. 20, no. 11-12, pp. 1008–1017, 2004. View at Publisher · View at Google Scholar · View at PubMed
  52. T. Tsuzuki, M. Igarashi, and T. Miyazawa, “Conjugated Eicosapentaenoic acid (EPA) inhibits transplanted tumor growth via membrane lipid peroxidation in nude mice,” Journal of Nutrition, vol. 134, no. 5, pp. 1162–1166, 2004. View at Google Scholar
  53. M. F. Andreoli, M. V. Scalerandi, I. M. Borel, and C. A. Bernal, “Effects of CLA at different dietary fat levels on the nutritional status of rats during protein repletion,” Nutrition, vol. 23, no. 11-12, pp. 827–835, 2007. View at Publisher · View at Google Scholar · View at PubMed
  54. J. Miranda, I. Churruca, A. Fernández-Quintela et al., “Weak effect of trans-10, cis-12-conjugated linoleic acid on body fat accumulation in adult hamsters,” British Journal of Nutrition, vol. 102, no. 11, pp. 1583–1589, 2009. View at Publisher · View at Google Scholar · View at PubMed
  55. A. Zabala, I. Churruca, A. Fernández-Quintela et al., “Trans-10,cis-12 conjugated linoleic acid inhibits lipoprotein lipase but increases the activity of lipogenic enzymes in adipose tissue from hamsters fed an atherogenic diet,” British Journal of Nutrition, vol. 95, no. 6, pp. 1112–1119, 2006. View at Publisher · View at Google Scholar
  56. M. T. Macarulla, A. Fernández-Quintela, A. Zabala et al., “Effects of conjugated linoleic acid on liver composition and fatty acid oxidation are isomer-dependent in hamster,” Nutrition, vol. 21, no. 4, pp. 512–519, 2005. View at Publisher · View at Google Scholar · View at PubMed
  57. V. Navarro, M. P. Portillo, A. Margotat et al., “A multi-gene analysis strategy identifies metabolic pathways targeted by trans-10, cis-12-conjugated linoleic acid in the liver of hamsters,” British Journal of Nutrition, vol. 102, no. 4, pp. 537–545, 2009. View at Publisher · View at Google Scholar · View at PubMed
  58. V. Bissonauth, Y. Chouinard, J. Marin, N. Leblanc, D. Richard, and H. Jacques, “The effects of t10,c12 CLA isomer compared with c9,t11 CLA isomer on lipid metabolism and body composition in hamsters,” Journal of Nutritional Biochemistry, vol. 17, no. 9, pp. 597–603, 2006. View at Publisher · View at Google Scholar · View at PubMed
  59. A. Lasa, E. Simón, I. Churruca et al., “Effects of trans-10,cis-12 CLA on liver size and fatty acid oxidation under energy restriction conditions in hamsters,” Nutrition, vol. 27, no. 1, pp. 116–121, 2011. View at Publisher · View at Google Scholar · View at PubMed
  60. E. Simón, M. T. MacArulla, I. Churruca, A. Fernández-Quintela, and M. P. Portillo, “trans-10,cis-12 Conjugated linoleic acid prevents adiposity but not insulin resistance induced by an atherogenic diet in hamsters,” Journal of Nutritional Biochemistry, vol. 17, no. 2, pp. 126–131, 2006. View at Publisher · View at Google Scholar · View at PubMed
  61. E. J. Tarling, K. J. P. Ryan, A. J. Bennett, and A. M. Salter, “Effect of dietary conjugated linoleic acid isomers on lipid metabolism in hamsters fed high-carbohydrate and high-fat diets,” British Journal of Nutrition, vol. 101, no. 11, pp. 1630–1638, 2009. View at Publisher · View at Google Scholar · View at PubMed
  62. E. A. M. De Deckere, J. M. M. Van Amelsvoort, G. P. McNeill, and P. Jones, “Effects of conjugated linoleic acid (CLA) isomers on lipid levels and peroxisome proliferation in the hamster,” British Journal of Nutrition, vol. 82, no. 4, pp. 309–317, 1999. View at Google Scholar
  63. E. Thom, J. Wadstein, and O. Gudmundsen, “Conjugated linoleic acid reduces body fat in healthy exercising humans,” Journal of International Medical Research, vol. 29, no. 5, pp. 392–396, 2001. View at Google Scholar
  64. K. L. Zambell, N. L. Keim, M. D. Van Loan et al., “Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure,” Lipids, vol. 35, no. 7, pp. 777–782, 2000. View at Google Scholar
  65. A. Petridou, V. Mougios, and A. Sagredos, “Supplementation with CLA: isomer incorporation into serum lipids and effect on body fat of women,” Lipids, vol. 38, no. 8, pp. 805–811, 2003. View at Publisher · View at Google Scholar
  66. C. Malpuech-Brugère, W. P. H. G. Verboeket-Van De Venne, R. P. Mensink et al., “Effects of two conjugated linoleic acid isomers on body fat mass in overweight humans,” Obesity Research, vol. 12, no. 4, pp. 591–598, 2004. View at Google Scholar
  67. G. Berven, A. Bye, O. Hals et al., “Safety of conjugated linoleic acid (CLA) in overweight or obese human volunteers,” European Journal of Lipid Science and Technology, vol. 102, no. 7, pp. 455–462, 2000. View at Google Scholar
  68. U. Risérus, B. Vessby, P. Arner, and B. Zethelius, “Supplementation with trans10cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity,” Diabetologia, vol. 47, no. 6, pp. 1016–1019, 2004. View at Google Scholar
  69. U. Riserus, P. Arner, K. Brismar et al., “Treatment with dietary trans10cis12 conjugated linoleic add causes isomerm-specific insulin resistance in obese men with the metabolic syndrome,” Diabetes Care, vol. 25, no. 9, pp. 1516–1521, 2002. View at Google Scholar
  70. S. Basu, U. Risérus, A. Turpeinen, and B. Vessby, “Conjugated linoleic acid induces lipid peroxidation in men with abdominal obesity,” Clinical Science, vol. 99, no. 6, pp. 511–516, 2000. View at Publisher · View at Google Scholar
  71. P. Benito, G. J. Nelson, D. S. Kelley, G. Bartolini, P. C. Schmidt, and V. Simon, “The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans,” Lipids, vol. 36, no. 3, pp. 229–236, 2001. View at Google Scholar
  72. V. Mougios, A. Matsakas, A. Petridou et al., “Effect of supplementation with conjugated linoleic acid on human serum lipids and body fat,” Journal of Nutritional Biochemistry, vol. 12, no. 10, pp. 585–594, 2001. View at Publisher · View at Google Scholar
  73. R. B. Kreider, M. P. Ferreira, M. Greenwood, M. Wilson, and A. L. Almada, “Effects of conjugated linoleic acid supplementation during resistance training on body composition, bone density, strength, and selected hematological markers,” Journal of Strength and Conditioning Research, vol. 16, no. 3, pp. 325–334, 2002. View at Publisher · View at Google Scholar · View at PubMed
  74. M. M. J. W. Kamphuis, M. P. G. M. Lejeune, W. H. M. Saris, and M. S. Westerterp-Plantenga, “Effect of conjugated linoleic acid supplementation after weight loss on appetite and food intake in overweight subjects,” European Journal of Clinical Nutrition, vol. 57, no. 10, pp. 1268–1274, 2003. View at Publisher · View at Google Scholar · View at PubMed
  75. F. Moloney, T. P. Yeow, A. Mullen, J. J. Nolan, and H. M. Roche, “Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus,” American Journal of Clinical Nutrition, vol. 80, no. 4, pp. 887–895, 2004. View at Google Scholar
  76. L. D. Whigham, M. O'Shea, I. C. M. Mohede, H. P. Walaski, and R. L. Atkinson, “Safety profile of conjugated linoleic acid in a 12-month trial in obese humans,” Food and Chemical Toxicology, vol. 42, no. 10, pp. 1701–1709, 2004. View at Publisher · View at Google Scholar
  77. J. M. Gaullier, J. Halse, K. Høye et al., “Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans,” Journal of Nutrition, vol. 135, no. 4, pp. 778–784, 2005. View at Google Scholar
  78. J. M. Gaullier, J. Halse, and K. Høye, “Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans (vol 79, pg 1118, 2004),” American Journal of Clinical Nutrition, vol. 81, no. 2, p. 538, 2005. View at Google Scholar
  79. J. S. W. Taylor, S. R. P. Williams, R. Rhys, P. James, and M. P. Frenneaux, “Conjugated linoleic acid impairs endothelial function,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 2, pp. 307–312, 2006. View at Publisher · View at Google Scholar · View at PubMed
  80. A. B. Thrush, A. Chabowski, G. J. Heigenhauser, B. W. McBride, M. Or-Rashid, and D. J. Dyck, “Conjugated linoleic acid increases skeletal muscle ceramide content and decreases insulin sensitivity in overweight, non-diabetic humans,” Applied Physiology, Nutrition and Metabolism, vol. 32, no. 3, pp. 372–382, 2007. View at Publisher · View at Google Scholar · View at PubMed
  81. N. M. Racine, A. C. Watras, A. L. Carrel et al., “Effect of conjugated linoleic acid on body fat accretion in overweight or obese children,” American Journal of Clinical Nutrition, vol. 91, no. 5, pp. 1157–1164, 2010. View at Publisher · View at Google Scholar · View at PubMed
  82. O. A. Gudbrandsen, E. Rodríguez, H. Wergedahl et al., “Trans-10, cis-12-conjugated linoleic acid reduces the hepatic triacylglycerol content and the leptin mRNA level in adipose tissue in obese Zucker fa/fa rats,” British Journal of Nutrition, vol. 102, no. 6, pp. 803–815, 2009. View at Publisher · View at Google Scholar · View at PubMed
  83. L. D. Whigham, A. C. Watras, and D. A. Schoeller, “Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans,” American Journal of Clinical Nutrition, vol. 85, no. 5, pp. 1203–1211, 2007. View at Google Scholar
  84. A. Bhattacharya, J. Banu, M. Rahman, J. Causey, and G. Fernandes, “Biological effects of conjugated linoleic acids in health and disease,” Journal of Nutritional Biochemistry, vol. 17, no. 12, pp. 789–810, 2006. View at Publisher · View at Google Scholar · View at PubMed
  85. H. Blankson, J. A. Stakkestad, H. Fagertun, E. Thom, J. Wadstein, and O. Gudmundsen, “Conjugated linoleic acid reduces body fat mass in overweight and obese humans,” Journal of Nutrition, vol. 130, no. 12, pp. 2943–2948, 2000. View at Google Scholar
  86. M. H. Cooper, J. R. Miller, P. L. Mitchell, D. L. Currie, and R. S. McLeod, “Conjugated linoleic acid isomers have no effect on atherosclerosis and adverse effects on lipoprotein and liver lipid metabolism in apoE-/- mice fed a high-cholesterol diet,” Atherosclerosis, vol. 200, no. 2, pp. 294–302, 2008. View at Publisher · View at Google Scholar · View at PubMed
  87. C. L. Gentile and M. J. Pagliassotti, “The endoplasmic reticulum as a potential therapeutic target in nonalcoholic fatty liver disease,” Current Opinion in Investigational Drugs, vol. 9, no. 10, pp. 1084–1088, 2008. View at Google Scholar
  88. F. Diraison and M. Beylot, “Role of human liver lipogenesis and reesterification in triglycerides secretion and in FFA reesterification,” American Journal of Physiology, vol. 274, no. 2, pp. E321–E327, 1998. View at Google Scholar
  89. K. L. Donnelly, C. I. Smith, S. J. Schwarzenberg, J. Jessurun, M. D. Boldt, and E. J. Parks, “Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease,” Journal of Clinical Investigation, vol. 115, no. 5, pp. 1343–1351, 2005. View at Publisher · View at Google Scholar
  90. U. A. Boelsterli and M. Bedoucha, “Toxicological consequences of altered peroxisome proliferator-activated receptor γ (PPARγ) expression in the liver: insights from models of obesity and type 2 diabetes,” Biochemical Pharmacology, vol. 63, no. 1, pp. 1–10, 2002. View at Publisher · View at Google Scholar
  91. P. Tontonoz, E. Hu, and B. M. Spiegelman, “Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor,” Cell, vol. 79, no. 7, pp. 1147–1156, 1994. View at Google Scholar
  92. Y. L. Zhang, A. Hernandez-Ono, P. Siri et al., “Aberrant hepatic expression of PPARγ2 stimulates hepatic lipogenesis in a mouse model of obesity, insulin resistance, dyslipidemia, and hepatic steatosis,” Journal of Biological Chemistry, vol. 281, no. 49, pp. 37603–37615, 2006. View at Publisher · View at Google Scholar · View at PubMed
  93. O. Gavrilova, M. Haluzik, K. Matsusue et al., “Liver peroxisome proliferator-activated receptor γ contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass,” Journal of Biological Chemistry, vol. 278, no. 36, pp. 34268–34276, 2003. View at Publisher · View at Google Scholar · View at PubMed
  94. P. D. Denechaud, P. Bossard, J. M. Lobaccaro et al., “LXR stimulates ChREBP expression but glucose is required its post-traductional activation,” Diabetes, vol. 56, p. A39, 2007. View at Google Scholar
  95. N. Guillén, M. A. Navarro, C. Arnal et al., “Microarray analysis of hepatic gene expression identifies new genes involved in steatotic liver,” Physiological Genomics, vol. 37, no. 3, pp. 187–198, 2009. View at Publisher · View at Google Scholar · View at PubMed
  96. X. Lin, J. J. Loor, and J. H. Herbein, “Trans10,cis12-18:2 is a more potent inhibitor of de novo fatty acid synthesis and desaturation than cis9,trans11-18:2 in the mammary gland of lactating mice,” Journal of Nutrition, vol. 134, no. 6, pp. 1362–1368, 2004. View at Google Scholar
  97. D. M. Stringer, P. Zahradka, V. C. DeClercq et al., “Modulation of lipid droplet size and lipid droplet proteins by trans-10,cis-12 conjugated linoleic acid parallels improvements in hepatic steatosis in obese, insulin-resistant rats,” Biochimica et Biophysica Acta, vol. 1801, no. 12, pp. 1375–1385, 2010. View at Publisher · View at Google Scholar · View at PubMed
  98. G. Musso, R. Gambino, G. Pacini, F. De Michieli, and M. Cassader, “Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of fatty liver,” American Journal of Clinical Nutrition, vol. 89, no. 2, pp. 558–567, 2009. View at Publisher · View at Google Scholar · View at PubMed
  99. H. Doege, R. A. Baillie, A. M. Ortegon et al., “Targeted deletion of FATP5 reveals multiple functions in liver metabolism: alterations in hepatic lipid homeostasis,” Gastroenterology, vol. 130, no. 4, pp. 1245–1258, 2006. View at Publisher · View at Google Scholar · View at PubMed
  100. S. L. Zhou, F. X. Ge, C. G. Hu et al., “Increased insulin- and leptin-regulated hepatocellular fatty acid uptake plays a major role in the pathogenesis of hepatic steatosis in mouse models with intact leptin signaling, but not in those lacking leptin (ob/ob) or the leptin receptor (db/db),” Hepatology, vol. 48, no. 4, p. 1161, 2008. View at Google Scholar
  101. M. A. Belury, S. Y. Moya-Camarena, M. Lu, L. Shi, L. M. Leesnitzer, and S. G. Blanchard, “Conjugated linoleic acid is an activator and ligand for peroxisome proliferator-activated receptor-gamma (PPARγ),” Nutrition Research, vol. 22, no. 7, pp. 817–824, 2002. View at Publisher · View at Google Scholar
  102. P. Degrace, B. Moindrot, I. Mohamed et al., “Upregulation of liver VLDL receptor and FAT/CD36 expression in LDLR −/− apoB100/100 mice fed trans-10,cis-12 conjugated linoleic acid,” Journal of Lipid Research, vol. 47, no. 12, pp. 2647–2655, 2006. View at Publisher · View at Google Scholar · View at PubMed
  103. A. Nagayoshi, N. Matsuki, H. Saito et al., “Defect in assembly process of very-low-density lipoprotein in suncus liver: an animal model of fatty liver,” Journal of Biochemistry, vol. 117, no. 4, pp. 787–793, 1995. View at Google Scholar
  104. Y. Lin, E. Schuurbiers, S. Van Der Veen, and E. A. M. De Deckere, “Conjugated linoleic acid isomers have differential effects on triglyceride secretion in Hep G2 cells,” Biochimica et Biophysica Acta, vol. 1533, no. 1, pp. 38–46, 2001. View at Publisher · View at Google Scholar
  105. J. K. Reddy and T. Hashimoto, “Peroxisomal β-oxidation and peroxisome proliferator - Activated receptor α: an adaptive metabolic system,” Annual Review of Nutrition, vol. 21, pp. 193–230, 2001. View at Publisher · View at Google Scholar · View at PubMed
  106. M. Javadi, A. C. Beynen, R. Hovenier et al., “Prolonged feeding of mice with conjugated linoleic acid increases hepatic fatty acid synthesis relative to oxidation,” Journal of Nutritional Biochemistry, vol. 15, no. 11, pp. 680–687, 2004. View at Publisher · View at Google Scholar · View at PubMed
  107. J. M. Chardigny, O. Hasselwander, M. Genty, K. Kraemer, A. Ptock, and J. L. Sébédio, “Effect of conjugated FA on feed intake, body composition, and liver FA in mice,” Lipids, vol. 38, no. 9, pp. 895–902, 2003. View at Publisher · View at Google Scholar
  108. D. S. Kelley, G. L. Bartolini, J. M. Warren, V. A. Simon, B. E. Mackey, and K. L. Erickson, “Contrasting effects of t10,c12- and c9,t11-conjugated linoleic acid isomers on the fatty acid profiles of mouse liver lipids,” Lipids, vol. 39, no. 2, pp. 135–141, 2004. View at Google Scholar
  109. D. S. Kelley, G. L. Bartolini, J. W. Newman, M. Vemuri, and B. E. Mackey, “Fatty acid composition of liver, adipose tissue, spleen, and heart of mice fed diets containing t10, c12-, and c9, t11-conjugated linoleic acid,” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 74, no. 5, pp. 331–338, 2006. View at Publisher · View at Google Scholar · View at PubMed
  110. S. V. Martins, P. A. Lopes, S. P. Alves et al., “Dietary conjugated linoleic acid isomers change the unsaturation degree of hepatic fatty acids in neutral lipids but not in polar lipids,” Nutrition Research, vol. 31, no. 3, pp. 246–254, 2011. View at Publisher · View at Google Scholar · View at PubMed
  111. J. L. Sébédio, E. Angioni, J. M. Chardigny, S. Grégoire, P. Juanéda, and O. Berdeaux, “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, vol. 36, no. 6, pp. 575–582, 2001. View at Google Scholar
  112. P. Puri, R. A. Baillie, M. M. Wiest et al., “A lipidomic analysis of nonalcoholic fatty liver disease,” Hepatology, vol. 46, no. 4, pp. 1081–1090, 2007. View at Publisher · View at Google Scholar · View at PubMed
  113. D. Wang, Y. Wei, and M. J. Pagliassotti, “Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis,” Endocrinology, vol. 147, no. 2, pp. 943–951, 2006. View at Publisher · View at Google Scholar · View at PubMed
  114. K. Eder, N. Slomma, and K. Becker, “Trans-10,cis-12 conjugated linoleic acid suppresses the desaturation of linoleic and α-linolenic acids in HepG2 cells,” Journal of Nutrition, vol. 132, no. 6, pp. 1115–1121, 2002. View at Google Scholar
  115. X. Lin, J. Bo, S. A. M. Oliver et al., “Dietary conjugated linoleic acid alters long chain polyunsaturated fatty acid metabolism in brain and liver of neonatal pigs,” The Journal of Nutritional Biochemistry. In press.
  116. M. Sugano, A. Tsujita, M. Yamasaki, M. Noguchi, and K. Yamada, “Conjugated linoleic acid modulates tissue levels of chemical mediators and immunoglobulins in rats,” Lipids, vol. 33, no. 5, pp. 521–527, 1998. View at Publisher · View at Google Scholar
  117. O. Y. Lukivskaya, A. A. Maskevich, and V. U. Buko, “Effect of ursodeoxycholic acid on prostaglandin metabolism and microsomal membranes in alcoholic fatty liver,” Alcohol, vol. 25, no. 2, pp. 99–105, 2001. View at Publisher · View at Google Scholar
  118. A. M. El-Badry, R. Graf, and P. A. Clavien, “Omega 3 - Omega 6: what is right for the liver?” Journal of Hepatology, vol. 47, no. 5, pp. 718–725, 2007. View at Publisher · View at Google Scholar · View at PubMed
  119. Y. Li and B. A. Watkins, “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, vol. 33, no. 4, pp. 417–425, 1998. View at Publisher · View at Google Scholar
  120. K. Eder, N. Slomma, K. Becker, and C. Brandsch, “Effect of linseed oil supplementation on concentrations of (n-3) polyunsaturated fatty acids in liver phospholipids of rats fed diets containing either an oil rich in conjugated linoleic acids, sunflower oil or high-oleic acid sunflower oil,” Journal of Animal Physiology and Animal Nutrition, vol. 89, no. 1-2, pp. 45–54, 2005. View at Publisher · View at Google Scholar
  121. S. Banni, A. Petroni, M. Blasevich et al., “Conjugated linoleic acids (CLA) as precursors of a distinct family of PUFA,” Lipids, vol. 39, no. 11, pp. 1143–1146, 2004. View at Publisher · View at Google Scholar
  122. J. M. Brown and M. K. McIntosh, “Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity,” Journal of Nutrition, vol. 133, no. 10, pp. 3041–3046, 2003. View at Google Scholar
  123. K. Kang, M. Miyazaki, J. M. Ntambi, and M. W. Pariza, “Evidence that the anti-obesity effect of conjugated linoleic acid is independent of effects on stearoyl-CoA desaturase1 expression and enzyme activity,” Biochemical and Biophysical Research Communications, vol. 315, no. 3, pp. 532–537, 2004. View at Publisher · View at Google Scholar · View at PubMed
  124. Y. Park, J. M. Storkson, J. M. Ntambi, M. E. Cook, C. J. Sih, and M. W. Pariza, “Inhibition of hepatic stearoyl-CoA desaturase activity by trans-10,cis- 12 conjugated linoleic acid and its derivatives,” Biochimica et Biophysica Acta, vol. 1486, no. 2-3, pp. 285–292, 2000. View at Publisher · View at Google Scholar
  125. J. M. Ntambi, M. Miyazaki, J. P. Stoehr et al., “Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 17, pp. 11482–11486, 2002. View at Publisher · View at Google Scholar · View at PubMed
  126. M. L. E. MacDonald, R. R. Singaraja, N. Bissada et al., “Absence of stearoyl-CoA desaturase-1 ameliorates features of the metabolic syndrome in LDLR-deficient mice,” Journal of Lipid Research, vol. 49, no. 1, pp. 217–229, 2008. View at Publisher · View at Google Scholar · View at PubMed
  127. M. Miyazaki, M. T. Flowers, H. Sampath et al., “Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis,” Cell Metabolism, vol. 6, no. 6, pp. 484–496, 2007. View at Publisher · View at Google Scholar · View at PubMed
  128. R. Gutiérrez-Juárez, A. Pocai, C. Mulas et al., “Critical role of stearoyl-CoA desaturase - 1 (SCD1) in the onset of diet-induced hepatic insulin resistance,” Journal of Clinical Investigation, vol. 116, no. 6, pp. 1686–1695, 2006. View at Publisher · View at Google Scholar · View at PubMed
  129. G. Jiang, Z. Li, F. Liu et al., “Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase-1,” Journal of Clinical Investigation, vol. 115, no. 4, pp. 1030–1038, 2005. View at Publisher · View at Google Scholar
  130. M. T. Flowers and J. M. Ntambi, “Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism,” Current Opinion in Lipidology, vol. 19, no. 3, pp. 248–256, 2008. View at Publisher · View at Google Scholar · View at PubMed
  131. R. L. House, J. P. Cassady, E. J. Eisen et al., “Functional genomic characterization of delipidation elicited by trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) in a polygenic obese line of mice,” Physiological Genomics, vol. 21, pp. 351–361, 2005. View at Publisher · View at Google Scholar · View at PubMed
  132. C. M. Reynolds and H. M. Roche, “Conjugated linoleic acid and inflammatory cell signalling,” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 82, no. 4–6, pp. 199–204, 2010. View at Publisher · View at Google Scholar · View at PubMed
  133. J. J. Senn, P. J. Klover, I. A. Nowak et al., “Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes,” Journal of Biological Chemistry, vol. 278, no. 16, pp. 13740–13746, 2003. View at Publisher · View at Google Scholar · View at PubMed
  134. P. A. Kern, G. B. Di Gregorio, T. Lu, N. Rassouli, and G. Ranganathan, “Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-α expression,” Diabetes, vol. 52, no. 7, pp. 1779–1785, 2003. View at Google Scholar
  135. N. Tsuboyama-Kasaoka, H. Miyazaki, S. Kasaoka, and O. Ezaki, “Increasing the amount of fat in a conjugated linoleic acid-supplemented diet reduces lipodystrophy in mice,” Journal of Nutrition, vol. 133, no. 6, pp. 1793–1799, 2003. View at Google Scholar
  136. K. Nagao, N. Inoue, Y. Ujino et al., “Effect of leptin infusion on insulin sensitivity and lipid metabolism in diet-induced lipodystrophy model mice,” Lipids in Health and Disease, vol. 7, article 8, 2008. View at Publisher · View at Google Scholar · View at PubMed
  137. M. Stout, L. Li, and M. Belury, “Hepatic steatosis by dietary-conjugated linoleic acid is accompanied by accumulation of diacylglycerol and increased membrane-associated protein kinase C ε in mice,” Molecular Nutrition and Food Research, vol. 55, no. 7, pp. 1010–1017, 2011. View at Publisher · View at Google Scholar · View at PubMed
  138. P. C. LaRosa, J. J. M. Riethoven, H. Chen et al., “Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes,” Physiological Genomics, vol. 31, no. 3, pp. 544–553, 2007. View at Publisher · View at Google Scholar · View at PubMed
  139. H. Poirier, I. Niot, L. Clément, M. Guerre-Millo, and P. Besnard, “Development of conjugated linoleic acid (CLA)-mediated lipoatrophic syndrome in the mouse,” Biochimie, vol. 87, no. 1, pp. 73–79, 2005. View at Publisher · View at Google Scholar · View at PubMed
  140. D. Oikawa, S. Tsuyama, Y. Akimoto, Y. Mizobe, and M. Furuse, “Arachidonic acid prevents fatty liver induced by conjugated linoleic acid in mice,” British Journal of Nutrition, vol. 101, no. 10, pp. 1558–1563, 2009. View at Publisher · View at Google Scholar · View at PubMed
  141. A. Ferramosca, V. Savy, L. Conte, and V. Zara, “Dietary combination of conjugated linoleic acid (CLA) and pine nut oil prevents CLA-induced fatty liver in mice,” Journal of Agricultural and Food Chemistry, vol. 56, no. 17, pp. 8148–8158, 2008. View at Publisher · View at Google Scholar · View at PubMed
  142. M. Vemuri, D. S. Kelley, and G. Bartolini, “Decosahexaenoic acid (DHA) but not eicosapentaenoic acid (EPA) reverses trans-10, cis-12-conjugated linoleic acid (t10, c12-CLA) induced insulin resistance in mice,” Faseb Journal, vol. 21, no. 5, p. A113, 2007. View at Google Scholar
  143. H. M. Roche, E. Noone, C. Sewter et al., “Isomer-dependent metabolic effects of conjugated linoleic acid: insights from molecular markers sterol regulatory element-binding protein-1c and LXRα,” Diabetes, vol. 51, no. 7, pp. 2037–2044, 2002. View at Google Scholar
  144. M. K. Mater, A. P. Thelen, and D. B. Jump, “Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression,” Journal of Lipid Research, vol. 40, no. 6, pp. 1045–1052, 1999. View at Google Scholar
  145. Y. Choi, Y. C. Kim, Y. B. Han, Y. Park, M. W. Pariza, and J. M. Ntambi, “The trans-10,cis-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 Adipocytes,” Journal of Nutrition, vol. 130, no. 8, pp. 1920–1924, 2000. View at Google Scholar
  146. J. S. Choi, I. U. Koh, M. H. Jung, and J. Song, “Effects of three different conjugated linoleic acid preparations on insulin signalling, fat oxidation and mitochondrial function in rats fed a high-fat diet,” British Journal of Nutrition, vol. 98, no. 2, pp. 264–275, 2007. View at Publisher · View at Google Scholar · View at PubMed
  147. B. De Roos, G. Rucklidge, M. Reid et al., “Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: a proteomics approach,” FASEB Journal, vol. 19, no. 12, pp. 1746–1748, 2005. View at Publisher · View at Google Scholar · View at PubMed