JBiSE  Vol.4 No.11 , November 2011
Compounds that inhibit triglyceride accumulation and TNFα secretion in adipocytes
ABSTRACT
Obese subjects show both a fatty predisposition and a higher risk of metabolic syndrome. This characteristic depends on adipocytes. However, the roles of adipocytes in metabolic syndrome have been insufficiently investigated, because few pure adipocyte cell lines have been isolated. The present study had two objectives: the isolation of a pure adipocyte cell line and clarification of the differences between adipocytes and preadipocytes, and screening for compounds that can potentially prevent metabolic syndrome. We isolated a novel adipocyte cell line, 3T3-L24. In the 3T3-L24 cells, the gene expression levels (of C/EBPα and β, PPARγ and AP2) and the production of triglyceride and TNFα were much higher than those in the preadipocyte 3T3-L1 cells. We used the 3T3-L24 adipocytes to screen for compounds that could inhibit triglyceride accumulation and TNFα secretion. Fatty acids enhanced the triglyceride accumulation. Sodium carboxylate, taurine and carnitine not only inhibited triglyceride accumulation, but also inhibited TNFα secretion. Therefore, these compounds might be effective to decrease the risk of metabolic syndrome in obese subjects.

Cite this paper
nullShiomi, N. , Maeda, M. and Mimura, M. (2011) Compounds that inhibit triglyceride accumulation and TNFα secretion in adipocytes. Journal of Biomedical Science and Engineering, 4, 684-691. doi: 10.4236/jbise.2011.411085.
References
[1]   Egusa, G., Murakami, F., Ito, C., Matsumoto, Y., Kado, S., Okamura, M., Mori, H., Yamane, K., Hara, H. and Yamakido, M. (1993) Westernized food habits and concentrations of serum lipids in the Japanese. Atherosclerosis, 100, 249-255. doi:10.1016/0021-9150(93)90211-C

[2]   Ahima, R.S. (2006) Adipose tissue as an endocrine organ. Obesity, 14, 242-249. doi:10.1038/oby.2006.317

[3]   Rosen, E.D. and Spiegelman, B.M. (2000) Molecular regulation of adipogenesis. Annual Review of Cell Biology, 16, 145- 171. doi:10.1146/annurev.cellbio.16.1.145

[4]   Matuzawa, Y. (2006) The metabolic syndrome and adipocytokines. FEBS Letters, 580, 2917-292. doi:10.1016/j.febslet.206.04.028

[5]   Maeda, K., Okubo, K., Shimomura, I., Funahashi T. and Matsuzawa, K. (1996). cDNA cloning and expression of novel adipose specific collagen-like factor apM1. Biochemical and Biophysical Research Communications, 221, 286-289.doi:10.1006/bbrc.1996.0587

[6]   Szkudelski, T. (2006) Intercellular mediators in regulation of leptin secretion from adipocytes. Physiological Research, 56, 503-512.

[7]   Hotamisligi, G.S., Peraldi, P., Budavari, A., Ellis, R., White, M.F. and Spiegelman, B.M. (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity induced insulin resistance. Science, 271, 665-668. doi:10.1126/science.271.5249.665

[8]   Yamaguchi, T., Kamo, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama- Kasaoka, N., Ezaki, O., Akanuma, Y., Gavrilova, O., Vinson, C., Reitman, M.L., Kagechika, H., Shudo, K., Yoda, M., Nakano, Y., Tobe, K., Nagai, R., Kimura, S., Tomita, M., Froguel, P. and Kadowaki, T. (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity, Nature Medicine, 7, 941-946. doi:10.1038/090984

[9]   Simomura, I., Hammer, R.E., Ikemoto, S., Brown, M.S. and Gorldstein, J.L. (1999) Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature, 401, 73-76. doi:10.1038/43448

[10]   Hotamisligil, G.S., Sharg, N.S. and Spiegelman, B.M. (1993) Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science, 259, 87-91. doi:10.1126/science.7678183

[11]   Bastard, J.P., Maachi, M., Lagathu, C., Kim, M.J., Caron, M., Vidal, H., Capeau, J. and Feve, B. (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. European Cytokine Network, 17, 4-12.

[12]   Minamimoto, T., Orimo, M., Shimizu, I., Kunieda, T., Yokoyama, M., Ito, T., Nojima, A., Nabetani, A., Oike, Y., Matsubara, H., Ishikawa, F. and Komuro, I. (2009) A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nature Medicine, 15, 1082-1087. doi:10.1038/nm.2014

[13]   Green, H. and, Kehinde, O. (1975) An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell, 5, 19-27. doi:10.1016/0092-8674(75)90087-2

[14]   Gregoire, F.M., Smas, C.M. and Sul, H.S. (1998) Understanding adipocyte differentiation. Physiologcal Review 78, 783-809.

[15]   Mimura, M., Nabeshima, R., Maeda, M. and Shiomi, N. (2008) A highly sensitive enzyme-linked immunosorbent assay for quantification of adipocytokines secreted by mouse adipocytes. Biochemical Engineering Journal, 43, 58-63. doi:10.1016/j.bej.2008.08.008

[16]   Tang, Q.Q. and Lane, M.D. (2000) Role of C/EBP homologous protein (CHOP-10) in the programmed activation of CCAAT/enhancer binding protein-β during adipogenesis. Proceeding of National Academy of Science in USA, 97, 12446-12450. doi:10.1073/pnas.220425597

[17]   Noon, L.A., Clark, A.K. and King P.J. (2004) A peroxisome proliferatore-response element in the murine mc2-γ promoter regulates its transcriptional activation during differentiation of 3T3-L1 adipocytes. Journal of Biological Chemistry, 279, 22803-22808. doi:10.1074/jbc.M401861200

[18]   Prusty, D., Park, B.H., Davis, K.E. and Farmer, S.R. (2002) Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferation-acti- vated receptor γ (PPARγ) and C/EBPα gene expression during the differentiation of 3T3-L1 preadipocytes. Journal of Biological Chemistry, 277, 46226-46232. doi:10.1074/jbc.M207776200

[19]   Wu, Z., Rosen, E.D., Brun, R., Hauser, S., Adelmat, G., Troy, A.E., Mckeon, C., Darlington, G.J. and Spiegelman, B.M. (1999) Cross-regulation of C/EBP alpha and PPARγ controls the transcriptional pathways of adipogenesis and insulin sensitivity. Molecular Cell, 3, 151-158. doi:10.1016/S1097-2765(00)80306-8

[20]   Ruderman N., Chisholm D., Pi-Sunyer X. and Schneider S. (1998) The metabolically obese, normal-weight individual revisited. Diabetes, 47, 699-713. doi:10.2337/diabetes.47.5.699

[21]   Ishikawa, M., Arai, S., Takano, M., Hamada, A., Kunimasa, K. and Mon, M. (2010) Taurin’s health influence on Japanese school girls. Journal of Biomedical Science, 17, S47. doi:10.1186/1423-0127-17-S1-S47

[22]   Kim, H.M., Do, C.H. and Lee D.H. (2010) Characterization of taurine as anti-obesity agent in C. elegans. Journal of Biomedical Science, 17, S33. doi:10.1186/1423-0127-17-S1-S33

[23]   Derosa, G., Maffioli, P., Ferrari, I., D’Angelo, A., Fogari, E., Palumbo, I., Randazzo, S. and Cicero, A.F. (2011) Orlistat and L-carnitine compared to orlistat alone on insulin resistance in obese diabetic patients. Endocrine Journal, 57, 777-786. doi:10.1507/emdocrj.K10E-049

[24]   Warensj?, E., Sundstr?m, J., Lind, L. and Vessby, B. (2006) Factor analysis of fatty acids in serum lipids as a measure of dietary fat quality in relation to the metabolic syndrome in men. American Journal of Clinical Nutrition, 84, 442-448.

[25]   Warensj?, E., Risèrus, U. and Vessby, B. (2005) Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men. Diabetologia, 48, 1999-2005. doi:10.1007/s00125-005-1897-x

[26]   Badley, R.L., Fisher, F.M. and Maratos-Fisher, E. (2008) Dietary acids differentially regulate production of TNF- alpha and IL-10 by murine 3T3-L1 adipocytes. Obesity, 16, 938-944. doi:10.1038/oby.2008.39

 
 
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