DOI QR코드

DOI QR Code

Effects of Melatonin and Fluid Shear Stress on 3T3-L1 Preadipocytes

3T3-L1 지방전구세포에서 멜라토닌과 유체전단응력의 영향

  • Lee, Jeongkun (Department of Biomedical Engineering, Yonsei University) ;
  • Lee, Yeong Hun (Department of Biomedical Engineering, Yonsei University) ;
  • Park, Chae Lim (Department of Biomedical Engineering, Yonsei University) ;
  • Kim, Chi Hyun (Department of Biomedical Engineering, Yonsei University)
  • 이정근 (연세대학교 보건과학대학 의공학부) ;
  • 이영훈 (연세대학교 보건과학대학 의공학부) ;
  • 박채림 (연세대학교 보건과학대학 의공학부) ;
  • 김지현 (연세대학교 보건과학대학 의공학부)
  • Received : 2018.03.29
  • Accepted : 2018.05.18
  • Published : 2018.06.30

Abstract

Obesity is a worldwide disease caused by the excessive proliferation of adipocytes. Multiple factors, including melatonin and physical loading, are involved in the control of obesity. Melatonin has been shown to induce apoptosis on preadipocytes while physical loading such as fluid shear stress (FSS) affects the proliferation and differentiation of adipocytes. Here, we studied the combined effects of melatonin and FSS on 3T3-L1 preadipocytes. For physical loading, preadipocytes were stimulated with a maximum dynamic fluid shear stress of 1 Pa at 1 Hz for 2 hours with/without melatonin. The experiment conditions were divided into four groups: (1) control, (2) 1 mM melatonin treatment, (3) FSS, and (4) combined 1 mM melatonin and FSS. All groups had a fixed duration time of 2 hours. ERK, p-ERK, COX-2, $C/EBP{\beta}$, $PPAR{\gamma}$, osteopontin, Bax, caspase-3 and caspase-8 proteins were assessed by Western blot analysis. GAPDH was used as a control. Results showed that combined melatonin and FSS treatment activated the ERK/MAPK pathway but not COX-2. Furthermore, combined melatonin and FSS treatment significantly decreased $C/EBP{\beta}$ and $PPAR{\gamma}$ compared to other groups. However, caspase-3 and caspase-8 did not result in significant changes. In summary, combined melatonin and FSS appears to have the potential to inhibit adipogenesis and treat obesity.

Keywords

References

  1. P.G. Kopelman, "Obesity as a medical problem," Nature, vol. 404, pp. 635-643, 2000. https://doi.org/10.1038/35007508
  2. X. Formiguera, and A. Canton, "Obesity: epidemiology and clinical aspects," Best Pract. Res. Clin. Gastroenterol., vol. 18, no. 6, pp. 1125-1146, 2004. https://doi.org/10.1016/S1521-6918(04)00091-5
  3. K.M. Flegal, M.D. Carroll, and B.K. Kit, "Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010," Jama., vol. 307, no. 5, pp. 491-497, 2012. https://doi.org/10.1001/jama.2012.39
  4. N.S. Wellman, and B. Friedberg, "Causes and consequences of adult obesity: health, social and economic impacts in the United States," Asia Pac. J. Clin. Nutr., vol. 11, no. 8, pp. 705-709, 2002. https://doi.org/10.1046/j.1440-6047.11.s8.6.x
  5. T. Furuyashiki, H. Nagayasu, Y. Aoki, H. Bessho, T. Hashimoto, K. Kanazawa, and H. Ashida, "Tea catechin suppresses adipocyte differentiation accompanied by down-regulation of $PPAR{\gamma}2$ and $C/EBP{\alpha}$ in 3T3-L1 cells," Biosci. Biotechnol. Biochem., vol. 68, no. 11, pp. 2353-2359, 2004. https://doi.org/10.1271/bbb.68.2353
  6. C. Weyer, J.E. Foley, C. Bogardus, P.A. Tataranni, and R.E. Pratley, "Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance," Diabetologia, vol. 43, no. 12, pp. 1498-1506, 2000. https://doi.org/10.1007/s001250051560
  7. Y.W. Wang, and P.J.H. Jones, "Conjugated linoleic acid and obesity control: efficacy and mechanisms," Int. J. Obes., vol. 28, no. 8, pp. 941-955, 2004. https://doi.org/10.1038/sj.ijo.0802641
  8. D.B. Hausman, M. DiGirolamo, T.J. Bartness, G.J. Hausman, and R.J. Martin, "The biology of white adipocyte proliferation," Obes. Rev., vol. 2, no. 4, pp. 239-254, 2001. https://doi.org/10.1046/j.1467-789X.2001.00042.x
  9. O.A. MacDougald, and S. Mandrup, "Adipogenesis: forces that tip the scales," Trends Endocrinol. Metab., vol. 13, no. 1, pp. 5-11, 2002. https://doi.org/10.1016/S1043-2760(01)00517-3
  10. H. Green, and O. Kehinde, "Sublines of mouse 3T3 cells that accumulate lipid," Cell, vol 1, no. 3, pp. 113-116, 1974. https://doi.org/10.1016/0092-8674(74)90126-3
  11. M.I. Lefterova, and M.A. Lazar, "New developments in adipogenesis," Trends Endocrinol. Metab., vol. 20, no. 3, pp. 107-114, 2009. https://doi.org/10.1016/j.tem.2008.11.005
  12. K. Vermeulen, D.R.V Bockstaele, and Z.N. Berneman, "Apoptosis: mechanisms and relevance in cancer," Ann. Hematol., vol. 84, no.10, pp. 627-639, 2005. https://doi.org/10.1007/s00277-005-1065-x
  13. K.J. Woo, Y.J. Jeong, J.W. Park, and T.K. Kwon, "Chrysininduced apoptosis is mediated through caspase activation and Akt inactivation in U937 leukemia cells," Biochem. Biophys. Res. Commun., vol. 325, no. 4, pp. 1215-1222, 2004. https://doi.org/10.1016/j.bbrc.2004.09.225
  14. M.O. Hengartner, "The biochemistry of apoptosis," Nature, vol. 407, pp. 770-776, 2000. https://doi.org/10.1038/35037710
  15. C.L. Hsu, and G.C. Yen, "Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells," J. Agric. Food Chem., vol. 55, no. 5, pp. 1730-1736, 2007. https://doi.org/10.1021/jf062912b
  16. S. Rayalam, J.Y. Yang, S. Ambati, M.A. Della-Fera, and C. A. Baile, "Resveratrol induces apoptosis and inhibits adipogenesis in 3T3?L1 adipocytes," Phytother. Res., vol. 22, no. 10, pp. 1367-1371, 2008. https://doi.org/10.1002/ptr.2503
  17. N. Shoham, and A. Gefen. "Mechanotransduction in adipocytes," J. Biomech., vol. 45, no. 1, pp. 1-8, 2012. https://doi.org/10.1016/j.jbiomech.2011.10.023
  18. R.M. Sainz, J.C. Mayo, C. Rodriguez, D.X. Tan, S. Lopez-Burillo, and R.J. Reiter, "Melatonin and cell death: differential actions on apoptosis in normal and cancer cells," Cell Mol. Life Sci., vol. 60, no. 7, pp. 1407-1426, 2003. https://doi.org/10.1007/s00018-003-2319-1
  19. D.E. Blask, L.A. Sauer, R.T. Dauchy, E.W. Holowachuk, M.S. Ruhoff, and H.S. Kopff, "Melatonin inhibition of cancer growth in vivo involves suppression of tumor fatty acid metabolism via melatonin receptor-mediated signal transduction events," Cancer res., vol. 59, no. 18, pp. 4693-4701, 1999.
  20. J.A. Roth, T. Rosenblatt, A. Lis, and R. Bucelli, "Melatonininduced suppression of PC12 cell growth is mediated by its Gi coupled transmembrane receptors," Brain res., vol. 919, no. 1, pp. 139-146, 2001. https://doi.org/10.1016/S0006-8993(01)03016-5
  21. D.L. Drazen, D. Bilu, S.D. Bilbo, and R.J. Nelson, "Melatonin enhancement of splenocyte proliferation is attenuated by luzindole, a melatonin receptor antagonist," Am. J. Physiol. Regul. Integr. Comp. Physiol., vol. 280, no. 5, pp. R1476-R1482, 2001. https://doi.org/10.1152/ajpregu.2001.280.5.R1476
  22. K. Zwirska-Korczala, J. Jochem, M. Adamczyk-Sowa, P. Sowa, R. Polaniak, E. Birkner, M. Latocha, K. Pilc, and R. Suchanek, "Influence of melatonin on cell proliferation, antioxidative enzyme activities and lipid peroxidation in 3T3-L1 preadipocytes-an in vitro study," J. Physiol. Pharmacol., vol. 56, pp. 91-99, 2005.
  23. H. Kato, G. Tanaka, S. Masuda, J. Ogasawara, T. Sakurai, T. Kizaki, H. Ohno, and T. Izawa, "Melatonin promotes adipogenesis and mitochondrial biogenesis in 3T3-L1 preadipocytes," J. Pineal. Res., vol. 59, no. 2, pp. 267-275, 2015. https://doi.org/10.1111/jpi.12259
  24. L. Zhang, P. Su, C. Xu, C. Chen, A. Liang, K. Du, Y. Peng, and D. Huang, "Melatonin inhibits adipogenesis and enhances osteogenesis of human mesenchymal stem cells by suppressing $PPAR{\gamma}$ expression and enhancing Runx2 expression," J. Pineal. Res., vol. 49, no. 4, pp. 364-372, 2010. https://doi.org/10.1111/j.1600-079X.2010.00803.x
  25. E. Linder-Ganz, N. Shabshin, Y. Itzchak, and A. Gefen, "Assessment of mechanical conditions in sub-dermal tissues during sitting: a combined experimental-MRI and finite element approach," J. Biomech., vol. 40, no. 7, pp. 1443-1454, 2007. https://doi.org/10.1016/j.jbiomech.2006.06.020
  26. Y. Hara, S. Wakino, Y. Tanabe, M. Saito, H. Tokuyama, N. Washida, S. Tatematsu, K. Yoshioka, K. Homma, K. Hasegawa, H. Minakuchi, K. Fujimura, K. Hosoya, K. Hayashi, K. Nakayama, and H. Itoh, "Rho and Rho-kinase activity in adipocytes contributes to a vicious cycle in obesity that may involve mechanical stretch," Sci. Signal., vol. 4, no. 157, pp. ra3, 2011. https://doi.org/10.1126/scisignal.2001227
  27. Y. Tanabe, M. Koga, M. Saito, Y. Matsunaga, and K. Nakayama, "Inhibition of adipocyte differentiation by mechanical stretching through ERK-mediated downregulation of $PPAR{\gamma}2$," J. Cell. Sci., vol. 117, no. 16, pp. 3605-3614, 2004. https://doi.org/10.1242/jcs.01207
  28. Y. Tanabe, Y. Matsunaga, M. Saito, and K. Nakayama, "Involvement of cyclooxygenase-2 in synergistic effect of cyclic stretching and eicosapentaenoic acid on adipocyte differentiation," J. Pharmacol. Sci., vol. 106, no. 3, pp. 478-484, 2008. https://doi.org/10.1254/jphs.FP0071886
  29. H. Huang, R.D. Kamm, and R.T. Lee. "Cell mechanics and mechanotransduction:pathways, probes, and physiology," Am. J. Physiol. Cell. Physiol., vol. 287, no. 1, pp. C1-C11, 2004. https://doi.org/10.1152/ajpcell.00559.2003
  30. T.M. Maul, D.W. Chew, A. Nieponice, and D.A. Vorp, "Mechanical stimuli differentially control stem cell behavior: morphology, proliferation, and differentiation," Biomech. Model. Mechanobiol., vol. 10, no. 6, pp. 939-953, 2011. https://doi.org/10.1007/s10237-010-0285-8
  31. L. Liu, W. Yuan, and J. Wang, "Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress," Biomech. Model. Mechanobiol., vol. 9, no. 6, pp. 659-670, 2010. https://doi.org/10.1007/s10237-010-0206-x
  32. C.H. Kim, L. You, C.E. Yellowley, and C.R. Jacobs, "Oscillatory fluid flow-induced shear stress decreases osteoclastogenesis through RANKL and OPG signaling," Bone, vol. 39, no. 5, pp. 1043-1047, 2006. https://doi.org/10.1016/j.bone.2006.05.017
  33. C.H. Kim, and Y.M. Yoo, "Fluid shear stress and melatonin in combination activate anabolic proteins in MC3T3-E1 osteoblast cells," J. Pineal Res., vol. 54, no. 4, pp. 453-461, 2013. https://doi.org/10.1111/jpi.12043
  34. M. Zeyda, K. Gollinger, J. Todoric, F.W. Kiefer, M. Keck, O. Aszmann, G. Prager, G.J. Zlabinger, P. Petzelbauer, and T.M. stulnig, "Osteopontin is an activator of human adipose tissue macrophages and directly affects adipocyte function," Endocrinology, vol. 152, no. 6, pp. 2219-2227, 2011. https://doi.org/10.1210/en.2010-1328
  35. F.M. Pavalko, R.L. Gerard, S.M. Ponik, P.J. Gallagher, Y. Jin, and S.M. Norvell, "Fluid shear stress inhibits TNF-${\alpha}$-induced apoptosis in osteoblasts: A role for fluid shear stress-induced activation of PI3-kinase and inhibition of caspase-3," J. Cell. Physiol., vol. 194, no. 2, pp. 194-205, 2003. https://doi.org/10.1002/jcp.10221