한국축산식품학회지 (Food Science of Animal Resources)

  • 제31권3호
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  • Pages.381-388
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  • 2011
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  • 2636-0772(pISSN)
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  • 2636-0780(eISSN)
한국축산식품학회 (Korean Society for Food Science of Animal Resources)
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Conjugated Linoleic Acid Negatively Regulates TR4 Activity in 3T3-L1 Adipocytes

  • Choi, Ho-Jung (Department of Biological Sciences, Chonnam National University) ;
  • Kim, Eung-Seok (Department of Biological Sciences, Chonnam National University)
  • 투고 : 2011.04.26
  • 심사 : 2011.05.25
  • 발행 : 2011.06.30
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초록

Dietary conjugated linoleic acid (CLA) play key roles in lipid metabolism. Here, we investigated the effect of CLA on the transcriptional activity of TR4, an orphan nuclear receptor that plays an important role in lipid homeostasis. CLA increased TR4 gene mRNA level in 3T3-L1 adipocytes, but inhibited TR4 transcriptional activity in a dose-dependent manner. TR4 induced perilipin expression in 3T3-L1 adipocytes by activating perilipin promoter activity. In a gel shift assay, TR4 bound direct to the putative TR4 response element in the perilipin promoter. Interestingly, CLA reduced the interaction between TR4 and consensus DR1, a well-known TR4 binding site. Additionally, CLA inhibited TR4-induced perilipin promoter activity in a dose-dependent manner. Together, our results suggest that CLA may play a role in lipid homeostasis in adipocytes by functionally regulating TR4.

키워드

참고문헌

  1. Alibin, C. P., Kopilas, M. A., and Anderson, H. D. (2008) Suppression of cardiac myocyte hypertrophy by conjugated linoleic acid: role of peroxisome proliferator-activated receptors alpha and gamma. J. Biol. Chem. 283, 10707-10715. https://doi.org/10.1074/jbc.M800035200
  2. Aouadi, M., Laurent, K., Prot, M., Le Marchand-Brustel, Y., Binetruy, B., and Bost, F. (2006) Inhibition of p38MAPK increases adipogenesis from embryonic to adult stages. Diabetes 55, 281-289. https://doi.org/10.2337/diabetes.55.02.06.db05-0963
  3. Arimura, N., Horiba, T., Imagawa, M., Shimizu, M., and Sato, R. (2004) The peroxisome proliferator-activated receptor gamma regulates expression of the perilipin gene in adipocytes. J. Biol. Chem. 279, 10070-10076. https://doi.org/10.1074/jbc.M308522200
  4. Bost, F., Aouadi, M., Caron, L., and Binetruy, B. (2005) The role of MAPKs in adipocyte differentiation and obesity. Biochimie 87, 51-56. https://doi.org/10.1016/j.biochi.2004.10.018
  5. Brasaemle, D. L., Rubin, B., Harten, I. A., Gruia-Gray, J., Kimmel, A. R., and Londos, C. (2000) Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis. J. Biol. Chem. 275, 38486-38493. https://doi.org/10.1074/jbc.M007322200
  6. Cariou, B., van Harmelen, K., Duran-Sandoval, D., van Dijk, T. H., Grefhorst, A., Abdelkarim, M., Caron, S., Torpier, G., Fruchart, J. C., Gonzalez, F. J., Kuipers, F., and Staels, B. (2006) The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J. Biol. Chem. 281, 11039-11049. https://doi.org/10.1074/jbc.M510258200
  7. Chen, S., Operana, T., Bonzo, J., Nguyen, N., and Tukey, R. H. (2005) ERK kinase inhibition stabilizes the aryl hydrocarbon receptor: implications for transcriptional activation and protein degradation. J. Biol. Chem. 280, 4350-4359. https://doi.org/10.1074/jbc.M411554200
  8. Chung, S., Brown, J. M., Sandberg, M. B., and McIntosh, M. (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, 885-895. https://doi.org/10.1194/jlr.M400476-JLR200
  9. Clement, L., Poirier, H., Niot, I., Bocher, V., Guerre-Millo, M., Krief, S., Staels, B., and Besnard, P. (2002) Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. J. Lipid Res. 43, 1400-1409. https://doi.org/10.1194/jlr.M20008-JLR200
  10. Evans, N. P., Misyak, S. A., Schmelz, E. M., Guri, A. J., Hontecillas, R., and Bassaganya-Riera, J. (2010) Conjugated linoleic acid ameliorates inflammation-induced colorectal cancer in mice through activation of PPARgamma. J. Nutr. 140, 515-521. https://doi.org/10.3945/jn.109.115642
  11. Granlund, L., Juvet, L. K., Pedersen, J. I., and Nebb, H. I. (2003) Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARgamma modulator. J. Lipid Res. 44, 1441-1452. https://doi.org/10.1194/jlr.M300120-JLR200
  12. Gregor, M. F. and Hotamisligil, G. S. (2007) Thematic review series: Adipocyte Biology. Adipocyte stress: the endoplasmic reticulum and metabolic disease. J. Lipid Res. 48, 1905-1914. https://doi.org/10.1194/jlr.R700007-JLR200
  13. Guilherme, A., Virbasius, J. V., Puri, V., and Czech, M. P. (2008) Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat. Rev. Mol. Cell Biol. 9, 367-377. https://doi.org/10.1038/nrm2391
  14. Ha, Y. L., Storkson, J., and Pariza, M. W. (1990) Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid. Cancer Res. 50, 1097-1101.
  15. Huq, M. D., Gupta, P., Tsai, N. P., and Wei, L. N. (2006) Modulation of testicular receptor 4 activity by mitogen-activated protein kinase-mediated phosphorylation. Mol. Cell Proteomics 5, 2072-2082. https://doi.org/10.1074/mcp.M600180-MCP200
  16. Kang, H. S., Okamoto, K., Kim, Y. S., Takeda, Y., Bortner, C. D., Dang, H., Wada, T., Xie, W., Yang, X. P., Liao, G., and Jetten, A. M. (2011) Nuclear orphan receptor TAK1/TR4- deficient mice are protected against obesity-linked inflammation, hepatic steatosis, and insulin resistance. Diabetes 60, 177-188. https://doi.org/10.2337/db10-0628
  17. Kang, K., Liu, W., Albright, K. J., Park, Y., and Pariza, M. W. (2003) trans-10,cis-12 CLA inhibits differentiation of 3T3-L1 adipocytes and decreases PPAR gamma expression. Biochem. Biophys. Res. Commun. 303, 795-799. https://doi.org/10.1016/S0006-291X(03)00413-3
  18. Kennedy, A., Chung, S., LaPoint, K., Fabiyi, O., and McIntosh, M. K. (2008) Trans-10, cis-12 conjugated linoleic acid antagonizes ligand-dependent PPARgamma activity in primary cultures of human adipocytes. J. Nutr. 138, 455-461.
  19. Kennedy, A., Overman, A., Lapoint, K., Hopkins, R., West, T., Chuang, C. C., Martinez, K., Bell, D., and McIntosh, M. (2009) Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol. J. Lipid Res. 50, 225-232.
  20. Kershaw, E. E. and Flier, J .S. (2004) Adipose tissue as an endocrine organ. J. Clin. Endocrinol. Metab. 89, 2548-2556 https://doi.org/10.1210/jc.2004-0395
  21. Kim, E., Liu, N. C., Yu, I. C., Lin, H. Y., Lee, Y. F., Sparks, J. D., Chen, L. M., and Chang, C. (2011) Metformin Inhibits Nuclear Receptor TR4-Mediated Hepatic Stearoyl-Coenzyme A Desaturase 1 Gene Expression With Altered Insulin Sensitivity. Diabetes DOI: 10.2337/db2310-0393.
  22. Kim, E., Xie, S., Yeh, S. D., Lee, Y. F., Collins, L. L., Hu, Y. C., Shyr, C. R., Mu, X. M., Liu, N. C., Chen, Y. T., Wang, P. H., and Chang, C. (2003) Disruption of TR4 orphan nuclear receptor reduces the expression of liver apolipoprotein E/C-I/C-II gene cluster. J. Biol. Chem. 278, 46919-46926. https://doi.org/10.1074/jbc.M304088200
  23. Kim, S. J., Choi, H., Jung, C. H., Park, S. S., Cho, S. R., Oh, S., and Kim, E. (2010) Calcium Mobilization Inhibits Lipid Accumulation During the Late Adipogenesis via Suppression of PPAR gamma and LXR alpha Signalings. Korean J. Food Sci. Ani. Resour. 30, 787-794. https://doi.org/10.5851/kosfa.2010.30.5.787
  24. Larsen, T. M., Toubro, S., and Astrup, A. (2003) Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. J. Lipid Res. 44, 2234-2241. https://doi.org/10.1194/jlr.R300011-JLR200
  25. Lee, H. J., Lee, Y., Burbach, J. P., and Chang, C. (1995) Suppression of gene expression on the simian virus 40 major late promoter by human TR4 orphan receptor. A member of the steroid receptor superfamily. J. Biol. Chem. 270, 30129-30133. https://doi.org/10.1074/jbc.270.50.30129
  26. Lee, K. N., Kritchevsky, D., and Pariza, M. W. (1994) Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis 108, 19-25. https://doi.org/10.1016/0021-9150(94)90034-5
  27. Lee, Y. F., Pan, H. J., Burbach, J. P., Morkin, E., and Chang, C. (1997) Identification of direct repeat 4 as a positive regulatory element for the human TR4 orphan receptor. A modulator for the thyroid hormone target genes. J. Biol. Chem. 272, 12215-12220. https://doi.org/10.1074/jbc.272.18.12215
  28. Lee, Y. F., Young, W. J., Lin, W. J., Shyr, C. R., and Chang, C. (1999) Differential regulation of direct repeat 3 vitamin D3 and direct repeat 4 thyroid hormone signaling pathways by the human TR4 orphan receptor. J. Biol. Chem. 274, 16198-16205. https://doi.org/10.1074/jbc.274.23.16198
  29. Miller, J. R., Siripurkpong, P., Hawes, J., Majdalawieh, A., Ro, H. S., and McLeod, R. S. (2008) The trans-10, cis-12 isomer of conjugated linoleic acid decreases adiponectin assembly by PPARgamma-dependent and PPARgamma-independent mechanisms. J. Lipid Res. 49, 550-562. https://doi.org/10.1194/jlr.M700275-JLR200
  30. Rosen, E. D. and Spiegelman, B. M. (2006) Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444, 847-853 https://doi.org/10.1038/nature05483
  31. Sakuma, S., Nishioka, Y., Imanishi, R., Nishikawa, K., Sakamoto, H., Fujisawa, J., Wada, K., Kamisaki, Y., and Fujimoto, Y. (2010) cis9, trans11-Conjugated linoleic acid differentiates mouse 3T3-L1 preadipocytes into mature small adipocytes through induction of peroxisome proliferator-activated receptor gamma. J. Clin. Biochem. Nutr. 47, 167-173. https://doi.org/10.3164/jcbn.10-44
  32. Shi, Y. and Burn, P. (2004) Lipid metabolic enzymes: emerging drug targets for the treatment of obesity. Nat. Rev. Drug Discov. 3, 695-710. https://doi.org/10.1038/nrd1469
  33. Tsai, N.P., Huq, M., Gupta, P., Yamamoto, K., Kagechika, H., and Wei, L. N. (2009) Activation of testicular orphan receptor 4 by fatty acids. Biochim. Biophys. Acta 1789, 734-740. https://doi.org/10.1016/j.bbagrm.2009.09.010
  34. Xie, S., Lee, Y. F., Kim, E., Chen, L. M., Ni, J., Fang, L. Y., Liu, S., Lin, S. J., Abe, J., Berk, B., Ho, F. M., and Chang, C. (2009) TR4 nuclear receptor functions as a fatty acid sensor to modulate CD36 expression and foam cell formation. P. Natl. Acad. Sci. USA 106, 13353-13358. https://doi.org/10.1073/pnas.0905724106

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