Molecules and Cells

  • 제41권10호
  • /
  • Pages.900-908
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  • 2018
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Effects of Three Thiazolidinediones on Metabolic Regulation and Cold-Induced Thermogenesis

  • Sohn, Jee Hyung (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University) ;
  • Kim, Jong In (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University) ;
  • Jeon, Yong Geun (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University) ;
  • Park, Jeu (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University) ;
  • Kim, Jae Bum (National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University)
  • 투고 : 2018.07.09
  • 심사 : 2018.08.03
  • 발행 : 2018.10.31
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초록

Insulin resistance is closely associated with metabolic diseases such as type 2 diabetes, dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones (TZDs) have been developed to ameliorate insulin resistance by activation of peroxisome proliferator-activated receptor (PPAR) ${\gamma}$. Although TZDs are synthetic ligands for $PPAR{\gamma}$, metabolic outcomes of each TZD are different. Moreover, there are lack of head-to-head comparative studies among TZDs in the aspect of metabolic outcomes. In this study, we analyzed the effects of three TZDs, including lobeglitazone (Lobe), rosiglitazone (Rosi), and pioglitazone (Pio) on metabolic and thermogenic regulation. In adipocytes, Lobe more potently stimulated adipogenesis and insulin-dependent glucose uptake than Rosi and Pio. In the presence of pro-inflammatory stimuli, Lobe efficiently suppressed expressions of pro-inflammatory genes in macrophages and adipocytes. In obese and diabetic db/db mice, Lobe effectively promoted insulin-stimulated glucose uptake and suppressed pro-inflammatory responses in epididymal white adipose tissue (EAT), leading to improve glucose intolerance. Compared to other two TZDs, Lobe enhanced beige adipocyte formation and thermogenic gene expression in inguinal white adipose tissue (IAT) of lean mice, which would be attributable to cold-induced thermogenesis. Collectively, these comparison data suggest that Lobe could relieve insulin resistance and enhance thermogenesis at low-concentration conditions where Rosi and Pio are less effective.

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참고문헌

  1. Ahmadian, M., Suh, J.M., Hah, N., Liddle, C., Atkins, A.R., Downes, M., and Evans, R.M. (2013). $PPAR{\gamma}$ signaling and metabolism: the good, the bad and the future. Nat. Med. 99, 557. https://doi.org/10.1038/nm.3159
  2. Alfadda, A.A., Sallam, R.M., Gul, R., Hwang, I., and Ka, S. (2017). Endophilin A2: a potential link to adiposity and beyond. Mol. Cells 40, 855-863.
  3. Berria, R., Glass, L., Mahankali, A., Miyazaki, Y., Monroy, A., De Filippis, E., Cusi, K., Cersosimo, E., Defronzo, R.A., and Gastaldelli, A. (2007). Reduction in hematocrit and hemoglobin following pioglitazone treatment is not hemodilutional in Type II diabetes mellitus. Clin. Pharmacol. Therap. 82, 275-281. https://doi.org/10.1038/sj.clpt.6100146
  4. Bouhlel, M.A., Derudas, B., Rigamonti, E., Dievart, R., Brozek, J., Haulon, S., Zawadzki, C., Jude, B., Torpier, G., Marx, N., et al. (2007). $PPAR{\gamma}$ activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metabol. 6, 137-143. https://doi.org/10.1016/j.cmet.2007.06.010
  5. Carriere, A., Jeanson, Y., Berger-Muller, S., Andre, M., Chenouard, V., Arnaud, E., Barreau, C., Walther, R., Galinier, A., Wdziekonski, B., et al. (2014). Browning of white adipose cells by intermediate metabolites: an adaptive mechanism to alleviate redox pressure. Diabetes 63, 3253-3265. https://doi.org/10.2337/db13-1885
  6. Choe, S.S., Huh, J.Y., Hwang, I.J., Kim, J.I., and Kim, J.B. (2016). Adipose tissue remodeling: its role in energy metabolism and metabolic disorders. Front. Endocrinol. 7, 30.
  7. Choi, J.H., Banks, A.S., Estall, J.L., Kajimura, S., Bostrom, P., Laznik, D., Ruas, J.L., Chalmers, M.J., Kamenecka, T.M., Bluher, M., et al. (2010). Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5. Nature 466, 451-456. https://doi.org/10.1038/nature09291
  8. Fonseca, V.A. (2009). Defining and characterizing the progression of type 2 diabetes. Diabetes Care 32 Suppl 2, S151-156. https://doi.org/10.2337/dc09-S301
  9. Gross, B., Pawlak, M., Lefebvre, P., and Staels, B. (2017). PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD. Nat. Rev. Endocrinol. 13, 36-49. https://doi.org/10.1038/nrendo.2016.135
  10. He, H., Tao, H., Xiong, H., Duan, S.Z., McGowan, F.X., Jr., Mortensen, R.M., and Balschi, J.A. (2014). Rosiglitazone causes cardiotoxicity via peroxisome proliferator-activated receptor gamma-independent mitochondrial oxidative stress in mouse hearts. Toxicol. Sci. 138, 468-481. https://doi.org/10.1093/toxsci/kfu015
  11. Huh, J.Y., Park, Y.J., Ham, M., and Kim, J.B. (2014). Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol. Cells 37, 365-371. https://doi.org/10.14348/molcells.2014.0074
  12. Ikeda, K., Maretich, P., and Kajimura, S. (2018). The common and distinct features of brown and beige adipocytes. Trends Endocrinol. Metabol. 29, 191-200. https://doi.org/10.1016/j.tem.2018.01.001
  13. Jang, J.Y., Bae, H., Lee, Y.J., Choi, Y.I., Kim, H.J., Park, S.B., Suh, S.W., Kim, S.W., and Han, B.W. (2018). Structural basis for the enhanced anti-diabetic efficacy of lobeglitazone on $PPAR{\gamma}$. Sci. Rep. 8, 31. https://doi.org/10.1038/s41598-017-18274-1
  14. Jenssen, T., and Hartmann, A. (2015). Emerging treatments for post-transplantation diabetes mellitus. Nat. Rev. Nephrol. 11, 465-477. https://doi.org/10.1038/nrneph.2015.59
  15. Jin, S.M., Park, C.Y., Cho, Y.M., Ku, B.J., Ahn, C.W., Cha, B.S., Min, K.W., Sung, Y.A., Baik, S.H., Lee, K.W., et al. (2015). Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group, active-controlled, phase III clinical trial with a 28-week extension. Diabetes Obes. Metabol. 17, 599-602. https://doi.org/10.1111/dom.12435
  16. Kahn, S.E., Haffner, S.M., Heise, M.A., Herman, W.H., Holman, R.R., Jones, N.P., Kravitz, B.G., Lachin, J.M., O'Neill, M.C., Zinman, B., et al. (2006). Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N. Engl J. Med. 355, 2427-2443. https://doi.org/10.1056/NEJMoa066224
  17. Kim, J.I., Huh, J.Y., Sohn, J.H., Choe, S.S., Lee, Y.S., Lim, C.Y., Jo, A., Park, S.B., Han, W., and Kim, J.B. (2015a). Lipid-overloaded enlarged adipocytes provoke insulin resistance independent of inflammation. Mol. Cell Biol. 35, 1686-1699. https://doi.org/10.1128/MCB.01321-14
  18. Kim, S.H., Kim, S.G., Kim, D.M., Woo, J.T., Jang, H.C., Chung, C.H., Ko, K.S., Park, J.H., Park, Y.S., Kim, S.J., et al. (2015b). Safety and efficacy of lobeglitazone monotherapy in patients with type 2 diabetes mellitus over 52 weeks: An open-label extension study. Diabetes Res. Clin. Pract. 110, e27-30. https://doi.org/10.1016/j.diabres.2015.09.009
  19. Kim, G., Lee, Y.H., Yun, M.R., Lee, J.Y., Shin, E.G., Lee, B.W., Kang, E.S., and Cha, B.S. (2017a). Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice. Int. J. Obes. 42, 545-551.
  20. Kim, K.M., Jin, H.J., Lee, S.Y., Maeng, H.J., Lee, G.Y., Oh, T.J., Choi, S.H., Jang, H.C., and Lim, S. (2017b). Effects of lobeglitazone, a new thiazolidinedione, on osteoblastogenesis and bone mineral density in mice. Endocrinol. Metabol. 32, 389-395. https://doi.org/10.3803/EnM.2017.32.3.389
  21. Kohlroser, J., Mathai, J., Reichheld, J., Banner, B.F., and Bonkovsky, H.L. (2000). Hepatotoxicity due to troglitazone: report of two cases and review of adverse events reported to the United States Food and Drug Administration. Am. J. Gastroenterol. 95, 272-276. https://doi.org/10.1111/j.1572-0241.2000.01707.x
  22. Lee, H.W., Kim, B.Y., Ahn, J.B., Kang, S.K., Lee, J.H., Shin, J.S., Ahn, S.K., Lee, S.J., and Yoon, S.S. (2005). Molecular design, synthesis, and hypoglycemic and hypolipidemic activities of novel pyrimidine derivatives having thiazolidinedione. Eur. J. Med. Chem. 40, 862-874. https://doi.org/10.1016/j.ejmech.2005.03.019
  23. Lee, J.H., Woo, Y.A., Hwang, I.C., Kim, C.Y., Kim, D.D., Shim, C.K., and Chung, S.J. (2009). Quantification of CKD-501, lobeglitazone, in rat plasma using a liquid-chromatography/tandem mass spectrometry method and its applications to pharmacokinetic studies. J. Pharm. Biomed. Anal. 50, 872-877. https://doi.org/10.1016/j.jpba.2009.06.003
  24. Lee, H.S., Chang, M., Lee, J.E., Kim, W., Hwang, I.C., Kim, D.H., Park, H.K., Choi, H.J., Jo, W., Cha, S.W., et al. (2014a). Carcinogenicity study of CKD-501, a novel dual peroxisome proliferator-activated receptors alpha and gamma agonist, following oral administration to Sprague Dawley rats for 94-101 weeks. Regul. Toxicol. Pharmacol. 69, 207-216. https://doi.org/10.1016/j.yrtph.2014.04.003
  25. Lee, J.H., Lee, G.Y., Jang, H., Choe, S.S., Koo, S.H., and Kim, J.B. (2014b). RNF20 regulates hepatic lipid metabolism through PKA-dependent SREBP1c degradation. Hepatology 60, 844-857. https://doi.org/10.1002/hep.27011
  26. Lee, M.A., Tan, L., Yang, H., Im, Y.G., and Im, Y.J. (2017). Structures of PPARgamma complexed with lobeglitazone and pioglitazone reveal key determinants for the recognition of antidiabetic drugs. Sci. Rep. 7, 16837. https://doi.org/10.1038/s41598-017-17082-x
  27. Lehmann, J.M., Moore, L.B., Smith-Oliver, T.A., Wilkison, W.O., Willson, T.M., and Kliewer, S.A. (1995). An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$). J. Biol. Chem. 270, 12953-12956. https://doi.org/10.1074/jbc.270.22.12953
  28. Li, Y., Wang, Z., Furukawa, N., Escaron, P., Weiszmann, J., Lee, G., Lindstrom, M., Liu, J., Liu, X., Xu, H., et al. (2008). T2384, a novel antidiabetic agent with unique peroxisome proliferator-activated receptor gamma binding properties. J. Biol. Chem. 283, 9168-9176. https://doi.org/10.1074/jbc.M800104200
  29. Lim, S., Lee, K.S., Lee, J.E., Park, H.S., Kim, K.M., Moon, J.H., Choi, S.H., Park, K.S., Kim, Y.B., and Jang, H.C. (2015). Effect of a new PPAR-gamma agonist, lobeglitazone, on neointimal formation after balloon injury in rats and the development of atherosclerosis. Atherosclerosis 243, 107-119. https://doi.org/10.1016/j.atherosclerosis.2015.08.037
  30. Moon, K.S., Lee, J.E., Lee, H.S., Hwang, I.C., Kim, D.H., Park, H.K., Choi, H.J., Jo, W., Son, W.C., and Yun, H.I. (2014). CKD-501, a novel selective PPARgamma agonist, shows no carcinogenic potential in ICR mice following oral administration for 104 weeks. J. Appl. Toxicol. 34, 1271-1284. https://doi.org/10.1002/jat.2918
  31. Nedergaard, J., Petrovic, N., Lindgren, E.M., Jacobsson, A., and Cannon, B. (2005). $PPAR{\gamma}$ in the control of brown adipocyte differentiation. Biochim. Biophys. Acta. 1740, 293-304. https://doi.org/10.1016/j.bbadis.2005.02.003
  32. Nissen, S.E., and Wolski, K. (2007). Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Eng. J. Med. 356, 2457-2471. https://doi.org/10.1056/NEJMoa072761
  33. Ohno, H., Shinoda, K., Spiegelman, B.M., and Kajimura, S. (2012). PPAR agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metabol. 15, 395-404. https://doi.org/10.1016/j.cmet.2012.01.019
  34. Olefsky, J.M., and Glass, C.K. (2010). Macrophages, inflammation, and insulin resistance. Ann. Rev. Physiol. 72, 219-246. https://doi.org/10.1146/annurev-physiol-021909-135846
  35. Qiang, L., Wang, L., Kon, N., Zhao, W., Lee, S., Zhang, Y., Rosenbaum, M., Zhao, Y., Gu, W., Farmer, S.R., et al. (2012). Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Ppargamma. Cell 150, 620-632. https://doi.org/10.1016/j.cell.2012.06.027
  36. Rizos, C.V., Elisaf, M.S., Mikhailidis, D.P., and Liberopoulos, E.N. (2009). How safe is the use of thiazolidinediones in clinical practice? Exp. Opin. Drug Safety 8, 15-32. https://doi.org/10.1517/14740330802597821
  37. Rothwell, N.J., Stock, M.J., and Tedstone, A.E. (1987). Effects of ciglitazone on energy balance, thermogenesis and brown fat activity in the rat. Mol. Cell. Endocrinol. 51, 253-257. https://doi.org/10.1016/0303-7207(87)90035-9
  38. Semple, R.K., Chatterjee, V.K., and O'Rahilly, S. (2006). PPAR gamma and human metabolic disease. J. Clin. Invest. 116, 581-589. https://doi.org/10.1172/JCI28003
  39. Soccio, R.E., Chen, E.R., and Lazar, M.A. (2014). Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes. Cell Metabol. 20, 573-591. https://doi.org/10.1016/j.cmet.2014.08.005
  40. Sohn, J.H., Lee, Y.K., Han, J.S., Jeon, Y.G., Kim, J.I., Choe, S.S., Kim, S.J., Yoo, H.J., and Kim, J.B. (2018). Perilipin 1 (Plin1) deficiency promotes inflammatory responses in lean adipose tissue through lipid dysregulation. J. Biol. Chem. pii: jbc.RA118.003541.
  41. Sola, D., Rossi, L., Schianca, G.P.C., Maffioli, P., Bigliocca, M., Mella, R., Corliano, F., Fra, G.P., Bartoli, E., and Derosa, G. (2015). Sulfonylureas and their use in clinical practice. Arch. Med. Sci. 11, 840-848.
  42. Taniguchi, C.M., Emanuelli, B., and Kahn, C.R. (2006). Critical nodes in signalling pathways: insights into insulin action. Nat. Rev. Mol. Cell Biol. 7, 85-96.
  43. Tontonoz, P., and Spiegelman, B.M. (2008). Fat and beyond: the diverse biology of PPARgamma. Ann. Rev. Biochem. 77, 289-312. https://doi.org/10.1146/annurev.biochem.77.061307.091829
  44. Yau, H., Rivera, K., Lomonaco, R., and Cusi, K. (2013). The future of thiazolidinedione therapy in the management of type 2 diabetes mellitus. Curr. Diabetes Rep. 13, 329-341. https://doi.org/10.1007/s11892-013-0378-8
  45. Yki-Jarvinen, H. (2004). Thiazolidinediones. N Engl. J. Med. 351, 1106-1118. https://doi.org/10.1056/NEJMra041001

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