Browse > Article
http://dx.doi.org/10.5851/kosfa.2010.30.5.787

Calcium Mobilization Inhibits Lipid Accumulation During the Late Adipogenesis via Suppression of PPARγ and LXRα Signalings  

Kim, Seung-Jin (Dept. of Biological sciences, College of Natural sciences, Chonnam National University)
Choi, Ho-Jung (Dept. of Biological sciences, College of Natural sciences, Chonnam National University)
Jung, Chung-Hwan (Dept. of Biological sciences, College of Natural sciences, Chonnam National University)
Park, Sung-Soo (Dept. of Biological sciences, College of Natural sciences, Chonnam National University)
Cho, Seung-Rye (Dept. of Biological sciences, College of Natural sciences, Chonnam National University)
Oh, Se-Jong (Division of Animal Science, College of Agriculture and Life Science, Chonnam National University)
Kim, Eung-Seok (Dept. of Biological sciences, College of Natural sciences, Chonnam National University)
Publication Information
Food Science of Animal Resources / v.30, no.5, 2010 , pp. 787-794 More about this Journal
Abstract
Calcium plays a role as a signaling molecule in various cellular events. It has been reported that calcium suppresses adipocyte differentiation only in the early phase of adipogenesis. Herein, we demonstrate that treatment of A23187, a mobilizer of intracellular calcium, on day 4 post adipocyte differentiation could still reduce lipid accumulation in differentiating 3T3-L1 cells for 48 h. In addition, luciferase reporter gene and RT-Q-PCR assays demonstrate that A23187 can selectively inhibit transcriptional activities and expression of PPAR$\gamma$ and LXR$\alpha$, suggesting that A23187 may reduce lipid accumulation in the late phase of adipogenesis via downregulation of PPAR$\gamma$ and LXR$\alpha$ expression and transactivation. Moreover, inhibition of HDAC activity by trichostatin A (TSA) partially blocked A23187-mediated downregulation of transcriptional activities of PPAR$\gamma$ and LXR$\alpha$. Together, our data demonstrate that calcium mobilization inhibits expression and transcriptional activities of PPAR$\gamma$ and LXR$\alpha$, resulting in reduced lipid accumulation in differentiating adipocytes, and thus, mobilization of intracellular calcium in adipocytes may serve as a new preventive and therapeutic approach for obesity.
Keywords
Calcium; adipocyte; PPAR$\gamma$; LXR$\alpha$;
Citations & Related Records

Times Cited By Web Of Science : 2  (Related Records In Web of Science)
Times Cited By SCOPUS : 0
연도 인용수 순위
  • Reference
1 Chen, G., Liang, G., Ou, J., Goldstein, J. L., and Brown, M. S. (2004) Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc. Natl. Acad Sci. USA 101, 11245-11250.   DOI   ScienceOn
2 Campbell, A. K. (1983) Intracellular calcium: Its universal role as regulator. John Wiley & Sons, Inc. Chichester; New York.
3 Shi, H., Halvorsen, Y. D., Ellis, P. N., Wilkison, W. O., and Zemel, M. B. (2000) Role of intracellular calcium in human adipocyte differentiation. Physiol Genomics. 3, 75-82.
4 Forman, B. M., Tontonoz, P., Chen, J., Brun, R. P., Spiegelman, B. M., and Evans, R. M. (1995) 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 83, 803-812.   DOI   ScienceOn
5 Volle, D. H., Mouzat, K., Duggavathi, R., Siddeek, B., Dechelotte, P., Sion, B., Veyssiere, G., Benahmed, M., and Lobaccaro, J. M. (2007) Multiple roles of the nuclear receptors for oxysterols liver X receptor to maintain male fertility. Mol. Endocrinol. 21, 1014-1027.   DOI   ScienceOn
6 Fu, M., Sun, T., Bookout, A. L., Downes, M., Yu, R. T., Evans, R. M., and Mangelsdorf, D. J. (2005) A Nuclear Receptor Atlas: 3T3-L1 adipogenesis. Mol. Endocrinol. 19, 2437-2450.   DOI   ScienceOn
7 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.   DOI   ScienceOn
8 Kim, H. B., Kong, M., Kim, T. M., Suh, Y. H., Kim, W. H., Lim, J. H., Song, J. H., and Jung, M. H. (2006) NFATc4 and ATF3 negatively regulate adiponectin gene expression in 3T3-L1 adipocytes. Diabetes. 55, 1342-1352.   DOI   ScienceOn
9 Laffitte, B. A., Joseph, S. B., Walczak, R., Pei, L., Wilpitz, D. C., Collins, J. L., and Tontonoz, P. (2001) Autoregulation of the human liver X receptor alpha promoter. Mol. Cell. Biol. 21, 7558-7568.   DOI   ScienceOn
10 Draznin, B., Sussman, K. E., Eckel, R. H., Kao, M., Yost, T., and Sherman, N. A. (1988) Possible role of cytosolic free calcium concentrations in mediating insulin resistance of obesity and hyperinsulinemia. J. Clin. Invest. 82, 1848-1852.   DOI
11 Rosen, E. D. and Spiegelman, B. M. (2006) Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 444, 847-853.   DOI   ScienceOn
12 Sekiya, M., Yahagi, N., Matsuzaka, T., Takeuchi, Y., Nakagawa, Y., Takahashi, H., Okazaki, H., Iizuka, Y., Ohashi, K., Gotoda, T., Ishibashi, S., Nagai, R., Yamazaki, T., Kadowaki, T., Yamada, N., Osuga, J., and Shimano, H. (2007) SREBP-1-independent regulation of lipogenic gene expression in adipocytes. J. Lipid. Res. 48, 1581-1591.   DOI   ScienceOn
13 Shi, Y. and Burn, P. (2004) Lipid metabolic enzymes: emerging drug targets for the treatment of obesity. Nat. Rev. Drug Discov. 3, 695-710.   DOI   ScienceOn
14 Szabo, E., Qiu, Y., Baksh, S., Michalak, M., and Opas, M. (2008) Calreticulin inhibits commitment to adipocyte differentiation. J. Cell Biol. 182, 103-116.   DOI   ScienceOn
15 Peet, D. J., Turley, S. D., Ma,W., Janowski, B. A., Lobaccaro, J. M., Hammer, R. E., and Mangelsdorf, D. J. (1998) Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR$\alpha$. Cell. 93, 693-704.   DOI   ScienceOn
16 Pilvi, T.K., Storvik, M., Louhelainen, M., Merasto, S., Korpela, R., and Mervaala, E. M. (2008) Effect of dietary calcium and dairy proteins on the adipose tissue gene expression profile in diet-induced obesity. J Nutrigenet Nutrigenomics. 1, 240-251.   DOI   ScienceOn
17 Moniotte, S., Kobzik, L., Feron, O., Trochu, J. N., Gauthier, C., and Balligand, J. L. (2001) Upregulation of beta(3)- adrenoceptors and altered contractile response to inotropic amines in human failing myocardium. Circulation. 103, 1649-1655.   DOI   ScienceOn
18 Rosen, E. D., Walkey, C. J., Puigserver, P., and Spiegelman, B. M. (2000) Transcriptional regulation of adipogenesis. Genes. Dev. 14, 1293-1307.
19 Schmid, B., Rippmann, J. F., Tadayyon, M., and Hamilton, B. S. (2005) Inhibition of fatty acid synthase prevents preadipocyte differentiation. Biochem. Biophys. Res. Commun. 328, 1073-1082.   DOI   ScienceOn
20 Liang, G., Yang, J., Horton, J. D., Hammer, R. E., Goldstein, J. L., and Brown, M. S. (2002) Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. J. Biol. Chem. 277, 9520-9528.   DOI   ScienceOn
21 Papakonstantinou, E., Flatt, W. P., Huth, P. J., and Harris, R. B. (2003) High dietary calcium reduces body fat content, digestibility of fat, and serum vitamin D in rats. Obes. Res. 11, 387-394.   DOI   ScienceOn
22 Kitamura, N., Wong, P., and Matsumura, F. (2006) Mechanistic investigation on the cause for reduced toxicity of TCDD in wa-1 homozygous TGFalpha mutant strain of mice as compared its matching wild-type counterpart, C57BL/6J mice. J. Biochem. Mol. Toxicol. 20, 151-158.   DOI   ScienceOn
23 Juvet, L. K., Andresen, S. M., Schuster, G. U., Dalen, K. T., Tobin, K. A., Hollung, K., Haugen, F., Jacinto, S., Ulven, S. M., Bamberg, K., Gustafsson, J. A., and Nebb, H. I. (2003) On the role of liver X receptors in lipid accumulation in adipocytes. Mol. Endocrinol. 17, 172-182.   DOI   ScienceOn
24 Kershaw, E. E. and Flier, J. S. (2004) Adipose tissue as an endocrine organ. J. Clin. Endocrinol. Metab. 89, 2548-2556   DOI   ScienceOn
25 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/CI/C-II gene cluster. J. Biol. Chem. 278, 46919-46926.   DOI   ScienceOn
26 Duffus, J. H. and Patterson, L. J. (1974) Control of cell division in yeast using the ionophore, A23187 with calcium and magnesium. Nature 251, 626-627.   DOI   ScienceOn
27 Lane, M. D., Tang, Q. Q., and Jiang, M. S. (1999) Role of the CCAAT enhancer binding proteins (C/EBPs) in adipocyte differentiation. Biochem. Biophys. Res. Commun. 266, 677-683.   DOI   ScienceOn
28 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.   DOI   ScienceOn
29 Jensen, B., Farach-Carson, M. C., Kenaley, E., and Akanbi, K. A. (2004) High extracellular calcium attenuates adipogenesis in 3T3-L1 preadipocytes. Exp. Cell Res. 301, 280-292.   DOI   ScienceOn
30 Joseph, S. B., Laffitte, B. A., Patel, P. H., Watson, M. A., Matsukuma, K. E., Walczak, R., Collins, J. L., Osborne, T. F., and Tontonoz, P. (2002) Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J. Biol. Chem. 277, 11019-11025.   DOI   ScienceOn
31 Evans, R. M. (1988) The steroid and thyroid hormone receptor superfamily. Science 240, 889-895.   DOI
32 Chawla, A., Schwarz, E. J., Dimaculangan, D. D., and Lazar, M. A. (1994) Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 135, 798-800.   DOI   ScienceOn
33 Giguere, V. (1999) Orphan nuclear receptors: from gene to function. Endocr. Rev. 20, 689-725.   DOI   ScienceOn
34 Gregoire, F. M., Smas, C. M., and Sul, H. S. (1998) Understanding adipocyte differentiation. Physiol. Rev. 78, 783-809
35 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.   DOI   ScienceOn
36 Zayzafoon, M. (2006) Calcium/calmodulin signaling controls osteoblast growth and differentiation. J. Cell Biochem. 97, 56-70.   DOI   ScienceOn
37 Darlington, G. J., Ross, S. E., and MacDougald, O. A. (1998) The role of C/EBP genes in adipocyte differentiation. J. Biol. Chem. 273, 30057-30060.   DOI
38 Berger, J., Tanen, M., Elbrecht, A., Hermanowski-Vosatka, A., Moller, D. E., Wright, S. D., and Thieringer, R. (2001) Peroxisome proliferator-activated receptor-gamma ligands inhibit adipocyte 11beta-hydroxysteroid dehydrogenase type 1 expression and activity. J. Biol. Chem. 276, 12629-12635.   DOI   ScienceOn
39 Berridge, M. J. (1993) Inositol trisphosphate and calcium signalling. Nature 361, 315-325.   DOI   ScienceOn
40 Whitehead, J. P., Molero, J. C., Clark, S., Martin, S., Meneilly, G., and James, D. E. (2001) The role of Ca2+ in insulin-stimulated glucose transport in 3T3-L1 cells. J. Biol. Chem. 276, 27816-27824.   DOI   ScienceOn