Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2014 (2014), Article ID 538183, 13 pages
http://dx.doi.org/10.1155/2014/538183
Research Article

Effects and Potential Mechanisms of Pioglitazone on Lipid Metabolism in Obese Diabetic KKAy Mice

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

Received 27 December 2013; Revised 20 February 2014; Accepted 20 February 2014; Published 31 March 2014

Academic Editor: Brian N. Finck

Copyright © 2014 Jun Peng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. F. Petersen and G. I. Shulman, “Etiology of insulin resistance,” American Journal of Medicine, vol. 119, no. 5, supplement 1, pp. S10–S16, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. S. Chitturi, S. Abeygunasekera, G. C. Farrell et al., “NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome,” Hepatology, vol. 35, no. 2, pp. 373–379, 2002. View at Publisher · View at Google Scholar · View at Scopus
  3. B. W. Smith and L. A. Adams, “Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment,” Nature Reviews Endocrinology, vol. 7, no. 8, pp. 456–465, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Tailleux, K. Wouters, and B. Staels, “Roles of PPARs in NAFLD: potential therapeutic targets,” Biochimica et Biophysica Acta, vol. 1821, no. 5, pp. 809–818, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. R. Belfort, S. A. Harrison, K. Brown et al., “A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis,” The New England Journal of Medicine, vol. 355, no. 22, pp. 2297–2307, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. M. J. Armstrong, D. D. Houlihan, and I. A. Rowe, “Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis,” The New England Journal of Medicine, vol. 363, no. 12, p. 1185, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. V. Ratziu, P. Giral, S. Jacqueminet et al., “Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial,” Gastroenterology, vol. 135, no. 1, pp. 100–110, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. D. B. Savage, “PPAR gamma as a metabolic regulator: insights from genomics and pharmacology,” Expert Reviews in Molecular Medicine, vol. 7, no. 1, pp. 1–16, 2005. View at Google Scholar
  9. M. Bedoucha, E. Atzpodien, and U. A. Boelsterli, “Diabetic KKAy mice exhibit increased hepatic PPARγ1 gene expression and develop hepatic steatosis upon chronic treatment with antidiabetic thiazolidinediones,” Journal of Hepatology, vol. 35, no. 1, pp. 17–23, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. R. Rahimian, E. Masih-Khan, M. Lo, C. Van Breemen, B. M. McManus, and G. P. Dubé, “Hepatic over-expression of peroxisome proliferator activated receptor γ2 in the ob/ob mouse model of non-insulin dependent diabetes mellitus,” Molecular and Cellular Biochemistry, vol. 224, no. 1-2, pp. 29–37, 2001. View at Publisher · View at Google Scholar · View at Scopus
  11. R. A. Memon, L. H. Tecott, K. Nonogaki et al., “Up-regulation of peroxisome proliferator-activated receptors (PPAR-α) and PPAR-γ messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-γ-responsive adipose tissue-specific genes in the liver of obese diabetic mice,” Endocrinology, vol. 141, no. 11, pp. 4021–4031, 2000. View at Google Scholar · View at Scopus
  12. O. Gavrilova, M. Haluzik, K. Matsusue et al., “Liver peroxisome proliferator-activated receptor γ contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass,” Journal of Biological Chemistry, vol. 278, no. 36, pp. 34268–34276, 2003. View at Publisher · View at Google Scholar · View at Scopus
  13. L. Chao, B. Marcus-Samuels, M. M. Mason et al., “Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones,” Journal of Clinical Investigation, vol. 106, no. 10, pp. 1221–1228, 2000. View at Google Scholar · View at Scopus
  14. K. Matsusue, M. Haluzik, G. Lambert et al., “Liver-specific disruption of PPARγ in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes,” Journal of Clinical Investigation, vol. 111, no. 5, pp. 737–747, 2003. View at Publisher · View at Google Scholar · View at Scopus
  15. E. Morán-Salvador, M. López-Parra, V. García-Alonso et al., “Role for PPARγ in obesity-induced hepatic steatosis as determined by hepatocyte- and macrophage-specific conditional knockouts,” The FASEB Journal, vol. 25, no. 8, pp. 2538–2550, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Yu, K. Matsusue, P. Kashireddy et al., “Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor γ1 (PPARγ1) overexpression,” Journal of Biological Chemistry, vol. 278, no. 1, pp. 498–505, 2003. View at Publisher · View at Google Scholar · View at Scopus
  17. I. García-Ruiz, C. Rodríguez-Juan, T. Díaz-Sanjuán, M. Á. Martínez, T. Muñoz-Yagüe, and J. A. Solís-Herruzo, “Effects of rosiglitazone on the liver histology and mitochondrial function in ob/ob mice,” Hepatology, vol. 46, no. 2, pp. 414–423, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. Y.-M. Nan, F. Han, L.-B. Kong et al., “Adenovirus-mediated peroxisome proliferator activated receptor gamma overexpression prevents nutritional fibrotic steatohepatitis in mice,” Scandinavian Journal of Gastroenterology, vol. 46, no. 3, pp. 358–369, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. C. W. Wu, E. S. H. Chu, C. N. Y. Lam et al., “PPARγ is essential for protection against nonalcoholic steatohepatitis,” Gene Therapy, vol. 17, no. 6, pp. 790–798, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. A. A. Gupte, J. Z. Liu, Y. Ren et al., “Rosiglitazone attenuates age- and diet-associated nonalcoholic steatohepatitis in male low-density lipoprotein receptor knockout mice,” Hepatology, vol. 52, no. 6, pp. 2001–2011, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Da Silva Morais, V. Lebrun, J. Abarca-Quinones et al., “Prevention of steatohepatitis by pioglitazone: implication of adiponectin-dependent inhibition of SREBP-1c and inflammation,” Journal of Hepatology, vol. 50, no. 3, pp. 489–500, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. V. Ratziu, F. Charlotte, C. Bernhardt et al., “Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the Fatty Liver Improvement by Rosiglitazone Therapy (FLIRT 2) extension trial,” Hepatology, vol. 51, no. 2, pp. 445–453, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. A. C. Calkin and P. Tontonoz, “Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR,” Nature Reviews Molecular Cell Biology, vol. 13, no. 4, pp. 213–224, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. S. H. Choi and H. N. Ginsberg, “Increased very low density lipoprotein (VLDL) secretion, hepatic steatosis, and insulin resistance,” Trends in Endocrinology and Metabolism, vol. 22, no. 9, pp. 353–363, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Nagashima, C. Lopez, D. Donovan et al., “Effects of the PPARγ agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus,” Journal of Clinical Investigation, vol. 115, no. 5, pp. 1323–1332, 2005. View at Publisher · View at Google Scholar · View at Scopus
  26. R. B. Goldberg, D. M. Kendall, M. A. Deeg et al., “A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia,” Diabetes Care, vol. 28, no. 7, pp. 1547–1554, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. M. A. Deeg, J. B. Buse, R. B. Goldberg et al., “Pioglitazone and rosiglitazone have different effects on serum lipoprotein particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia,” Diabetes Care, vol. 30, no. 10, pp. 2458–2464, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. Y. Takahashi, Y. Soejima, and T. Fukusato, “Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis,” World Journal of Gastroenterology, vol. 18, no. 19, pp. 2300–2308, 2012. View at Google Scholar
  29. K. Srinivasan and P. Ramarao, “Animal models in type 2 diabetes research: an overview,” Indian Journal of Medical Research, vol. 125, no. 3, pp. 451–472, 2007. View at Google Scholar · View at Scopus
  30. L. Yvan-Charvet, M. Ranalletta, N. Wang et al., “Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice,” Journal of Clinical Investigation, vol. 117, no. 12, pp. 3900–3908, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. W. T. Friedewald, R. I. Levy, and D. S. Fredrickson, “Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge,” Clinical Chemistry, vol. 18, no. 6, pp. 499–502, 1972. View at Google Scholar · View at Scopus
  32. K. Matsusue, T. Kusakabe, T. Noguchi et al., “Hepatic steatosis in leptin-deficient mice is promoted by the PPARγ target gene Fsp27,” Cell Metabolism, vol. 7, no. 4, pp. 302–311, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. J. Ye and R. A. DeBose-Boyd, “Regulation of cholesterol and fatty acid synthesis,” Cold Spring Harbor Perspectives in Biology, vol. 3, no. 7, 2011. View at Publisher · View at Google Scholar · View at Scopus
  34. S. Mandard, M. Müller, and S. Kersten, “Peroxisome proliferator-activated receptor α target genes,” Cellular and Molecular Life Sciences, vol. 61, no. 4, pp. 393–416, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. S. M. Watkins, P. R. Reifsnyder, H.-J. Pan, J. Bruce German, and E. H. Leiter, “Lipid metabolome-wide effects of the PPARγ agonist rosiglitazone,” The Journal of Lipid Research, vol. 43, no. 11, pp. 1809–1817, 2002. View at Publisher · View at Google Scholar · View at Scopus
  36. C.-L. E. Yen, S. J. Stone, S. Koliwad, C. Harris, and R. V. Farese Jr., “DGAT enzymes and triacylglycerol biosynthesis,” Journal of Lipid Research, vol. 49, no. 11, pp. 2283–2301, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. M. M. Hussain, P. Rava, M. Walsh, M. Rana, and J. Iqbal, “Multiple functions of microsomal triglyceride transfer protein,” Nutrition and Metabolism, vol. 9, article 14, 2012. View at Publisher · View at Google Scholar · View at Scopus
  38. C. N. A. Palmer, M.-H. Hsu, K. J. Griffin, J. L. Raucy, and E. F. Johnson, “Peroxisome proliferator activated receptor-α expression in human liver,” Molecular Pharmacology, vol. 53, no. 1, pp. 14–22, 1998. View at Google Scholar · View at Scopus
  39. T. F. Daniels, K. M. Killinger, J. J. Michal, R. W. Wright Jr., and Z. Jiang, “Lipoproteins, cholesterol homeostasis and cardiac health,” International Journal of Biological Sciences, vol. 5, no. 5, pp. 474–488, 2009. View at Google Scholar · View at Scopus
  40. C. Chatterjee and D. L. Sparks, “Hepatic lipase, high density lipoproteins, and hypertriglyceridemia,” American Journal of Pathology, vol. 178, no. 4, pp. 1429–1433, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. W. Annema and U. J. F. Tietge, “Role of hepatic lipase and endothelial lipase in high-density lipoprotein-mediated reverse cholesterol transport,” Current Atherosclerosis Reports, vol. 13, no. 3, pp. 257–265, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. L. Djaouti, T. Jourdan, L. Demizieux et al., “Different effects of pioglitazone and rosiglitazone on lipid metabolism in mouse cultured liver explants,” Diabetes/Metabolism Research and Reviews, vol. 26, no. 4, pp. 297–305, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. C. Joyce, L. Freeman, H. B. Brewer Jr., and S. Santamarina-Fojo, “Study of ABCA1 function in transgenic mice,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 6, pp. 965–971, 2003. View at Publisher · View at Google Scholar · View at Scopus
  44. J.-Y. Lee and J. S. Parks, “ATP-binding cassette transporter Al and its role in HDL formation,” Current Opinion in Lipidology, vol. 16, no. 1, pp. 19–25, 2005. View at Google Scholar · View at Scopus
  45. D. A. Mogilenko, V. S. Shavva, E. B. Dizhe, S. V. Orlov, and A. P. Perevozchikov, “PPARγ activates ABCA1 gene transcription but reduces the level of ABCA1 protein in HepG2 cells,” Biochemical and Biophysical Research Communications, vol. 402, no. 3, pp. 477–482, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. A. Baldán, D. D. Bojanic, and P. A. Edwards, “The ABCs of sterol transport,” Journal of Lipid Research, vol. 50, pp. S80–S85, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. C. Funk, C. Ponelle, G. Scheuermann, and M. Pantze, “Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity: in vivo and in vitro interaction at the canalicular bile salt export pump (Bsep) in the rat,” Molecular Pharmacology, vol. 59, no. 3, pp. 627–635, 2001. View at Google Scholar · View at Scopus
  48. C. Funk, M. Pantze, L. Jehle et al., “Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export of bile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and the inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate,” Toxicology, vol. 167, no. 1, pp. 83–98, 2001. View at Publisher · View at Google Scholar · View at Scopus