Table of Contents Author Guidelines Submit a Manuscript
Experimental Diabetes Research
Volume 2012, Article ID 716425, 16 pages
http://dx.doi.org/10.1155/2012/716425
Review Article

Role of Transcription Factor Modifications in the Pathogenesis of Insulin Resistance

1Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea
2Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea
3Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea

Received 26 May 2011; Accepted 25 July 2011

Academic Editor: Faidon Magkos

Copyright © 2012 Mi-Young Kim 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. J. E. Darnell Jr., “Variety in the level of gene control in eukaryotic cells,” Nature, vol. 297, no. 5865, pp. 365–371, 1982. View at Publisher · View at Google Scholar · View at Scopus
  2. E. H. Davidson, H. T. Jacobs, and R. J. Britten, “Very short repeats and coordinate induction of genes,” Nature, vol. 301, no. 5900, pp. 468–470, 1983. View at Publisher · View at Google Scholar · View at Scopus
  3. D. P. McDonnell, Z. Nawaz, and B. W. O'Malley, “In situ distinction between steroid receptor binding and transactivation at a target gene,” Molecular and Cellular Biology, vol. 11, no. 9, pp. 4350–4355, 1991. View at Google Scholar · View at Scopus
  4. D. P. McDonnell, E. Vegeto, and B. W. O'Malley, “Identification of a negative regulatory function for steroid receptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 22, pp. 10563–10567, 1992. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Li and Y. Shang, “Regulation of SRC family coactivators by post-translational modifications,” Cellular Signalling, vol. 19, no. 6, pp. 1101–1112, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. P. Zimmet, K. G. M. M. Alberti, and J. Shaw, “Global and societal implications of the diabetes epidemic,” Nature, vol. 414, no. 6865, pp. 782–787, 2001. View at Publisher · View at Google Scholar · View at Scopus
  7. D. Porte Jr., “Banting lecture 1990. β-cells in type II diabetes mellitus,” Diabetes, vol. 40, no. 2, pp. 166–180, 1991. View at Google Scholar
  8. C. R. Kahn, “Banting lecture: insulin action, diabetogenes, and the cause of type II diabetes,” Diabetes, vol. 43, no. 8, pp. 1066–1084, 1994. View at Google Scholar · View at Scopus
  9. G. M. Reaven, “Pathophysiology of insulin resistance in human disease,” Physiological Reviews, vol. 75, no. 3, pp. 473–486, 1995. View at Google Scholar · View at Scopus
  10. D. M. Muoio and C. B. Newgard, “Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes,” Nature Reviews Molecular Cell Biology, vol. 9, no. 3, pp. 193–205, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. J. A. Kim, Y. Wei, and J. R. Sowers, “Role of mitochondrial dysfunction in insulin resistance,” Circulation Research, vol. 102, no. 4, pp. 401–414, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. D. L. Eizirik, A. K. Cardozo, and M. Cnop, “The role for endoplasmic reticulum stress in diabetes mellitus,” Endocrine Reviews, vol. 29, no. 1, pp. 42–61, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. M. P. Wymann and R. Schneiter, “Lipid signalling in disease,” Nature Reviews Molecular Cell Biology, vol. 9, no. 2, pp. 162–176, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. S. E. Shoelson, J. Lee, and A. B. Goldfine, “Inflammation and insulin resistance,” Journal of Clinical Investigation, vol. 116, no. 7, pp. 1793–1801, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. L. P. van der Heide and M. P. Smidt, “Regulation of FoxO activity by CBP/p300-mediated acetylation,” Trends in Biochemical Sciences, vol. 30, no. 2, pp. 81–86, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. T. Hunter and M. Karin, “The regulation of transcription by phosphorylation,” Cell, vol. 70, no. 3, pp. 375–387, 1992. View at Publisher · View at Google Scholar · View at Scopus
  17. A. J. Whitmarsh and R. J. Davis, “Regulation of transcription factor function by phosphorylation,” Cellular and Molecular Life Sciences, vol. 57, no. 8-9, pp. 1172–1183, 2000. View at Google Scholar · View at Scopus
  18. G. W. Hart, M. P. Housley, and C. Slawson, “Cycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins,” Nature, vol. 446, no. 7139, pp. 1017–1022, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. Y. Hu, J. Suarez, E. Fricovsky et al., “Increased enzymatic O-GlcNAcylation of mitochondrial proteins impairs mitochondrial function in cardiac myocytes exposed to high glucose,” Journal of Biological Chemistry, vol. 284, no. 1, pp. 547–555, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. D. C. Love, J. Kochran, R. L. Cathey, S. H. Shin, and J. A. Hanover, “Mitochondrial and nucleocytoplasmic targeting of O-linked GlcNAc transferase,” Journal of Cell Science, vol. 116, part 4, pp. 647–654, 2003. View at Publisher · View at Google Scholar
  21. T. Issad and M. Kuo, “O-GlcNAc modification of transcription factors, glucose sensing and glucotoxicity,” Trends in Endocrinology and Metabolism, vol. 19, no. 10, pp. 380–389, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. T. Lefebvre, V. Dehennaut, C. Guinez et al., “Dysregulation of the nutrient/stress sensor O-GlcNAcylation is involved in the etiology of cardiovascular disorders, type-2 diabetes and Alzheimer's disease,” Biochimica et Biophysica Acta, vol. 1800, no. 2, pp. 67–79, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. R. C. Conaway, C. S. Brower, and J. W. Conaway, “Emerging roles of ubiquitin in transcription regulation,” Science, vol. 296, no. 5571, pp. 1254–1258, 2002. View at Publisher · View at Google Scholar · View at Scopus
  24. M. H. Glickman and A. Ciechanover, “The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction,” Physiological Reviews, vol. 82, no. 2, pp. 373–428, 2002. View at Google Scholar · View at Scopus
  25. M. Muratani and W. P. Tansey, “How the ubiquitin-proteasome system controls transcription,” Nature Reviews Molecular Cell Biology, vol. 4, no. 3, pp. 192–201, 2003. View at Publisher · View at Google Scholar · View at Scopus
  26. G. Gill, “Something about SUMO inhibits transcription,” Current Opinion in Genetics and Development, vol. 15, no. 5, pp. 536–541, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. G. Gill, “Post-translational modification by the small ubiquitin-related modifier SUMO has big effects on transcription factor activity,” Current Opinion in Genetics and Development, vol. 13, no. 2, pp. 108–113, 2003. View at Publisher · View at Google Scholar · View at Scopus
  28. J. S. Seeler and A. Dejean, “Nuclear and unclear functions of SUMO,” Nature Reviews Molecular Cell Biology, vol. 4, no. 9, pp. 690–699, 2003. View at Publisher · View at Google Scholar · View at Scopus
  29. H. Braun, R. Koop, A. Ertmer, S. Nacht, and G. Suske, “Transcription factor Sp3 is regulated by acetylation,” Nucleic Acids Research, vol. 29, no. 24, pp. 4994–5000, 2001. View at Google Scholar · View at Scopus
  30. J. M. P. Desterro, M. S. Rodriguez, and R. T. Hay, “SUMO-1 modification of IκBα inhibits NF-κB activation,” Molecular Cell, vol. 2, no. 2, pp. 233–239, 1998. View at Google Scholar · View at Scopus
  31. M. Balasubramanyam, R. Sampathkumar, and V. Mohan, “Is insulin signaling molecules misguided in diabetes for ubiquitin-proteasome mediated degradation?” Molecular and Cellular Biochemistry, vol. 275, no. 1-2, pp. 117–125, 2005. View at Publisher · View at Google Scholar · View at Scopus
  32. R. K. Hall and D. K. Granner, “Insulin regulates expression of metabolic genes through divergent signaling pathways,” Journal of Basic and Clinical Physiology and Pharmacology, vol. 10, no. 2, pp. 119–133, 1999. View at Google Scholar · View at Scopus
  33. A. Brunet, A. Bonni, M. J. Zigmond et al., “Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor,” Cell, vol. 96, no. 6, pp. 857–868, 1999. View at Google Scholar · View at Scopus
  34. J. Nakae, B. C. Park, and D. Accili, “Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a wortmannin-sensitive pathway,” Journal of Biological Chemistry, vol. 274, no. 23, pp. 15982–15985, 1999. View at Publisher · View at Google Scholar · View at Scopus
  35. P. K. Vogt, H. Jiang, and M. Aoki, “Triple layer control: phosphorylation, acetylation and ubiquitination of FOXO proteins,” Cell Cycle, vol. 4, no. 7, pp. 908–913, 2005. View at Google Scholar · View at Scopus
  36. J. E. Ayala, R. S. Streeper, J. S. Desgrosellier et al., “Conservation of an insulin response unit between mouse and human glucose-6-phosphatase catalytic subunit gene promoters: transcription factor FKHR binds the insulin response sequence,” Diabetes, vol. 48, no. 9, pp. 1885–1889, 1999. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Barthel, D. Schmoll, K. D. Krüger et al., “Differential regulation of endogenous glucose-6-phosphatase and phosphoenolpyruvate carboxykinase gene expression by the forkhead transcription factor FKHR in H4IIE-hepatoma cells,” Biochemical and Biophysical Research Communications, vol. 285, no. 4, pp. 897–902, 2001. View at Publisher · View at Google Scholar
  38. H. Daitoku, K. Yamagata, H. Matsuzaki, M. Hatta, and A. Fukamizu, “Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR,” Diabetes, vol. 52, no. 3, pp. 642–649, 2003. View at Publisher · View at Google Scholar · View at Scopus
  39. G. Rena, G. Shaodong, S. C. Cichy, T. G. Unterman, and P. Cohen, “Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B,” Journal of Biological Chemistry, vol. 274, no. 24, pp. 17179–17183, 1999. View at Publisher · View at Google Scholar · View at Scopus
  40. H. Huang, K. M. Regan, Z. Lou, J. Chen, and D. J. Tindall, “CDK2-dependent phosphorylation of FOXO1 as an apoptotic response to DNA damage,” Science, vol. 314, no. 5797, pp. 294–297, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. G. Rena, J. Bain, M. Elliott, and P. Cohen, “D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a,” EMBO Reports, vol. 5, no. 1, pp. 60–65, 2004. View at Publisher · View at Google Scholar · View at Scopus
  42. Y. L. Woods, G. Rena, N. Morrice et al., “The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site,” Biochemical Journal, vol. 355, part 3, pp. 597–607, 2001. View at Google Scholar · View at Scopus
  43. G. Rena, A. R. Prescott, S. Guo, P. Cohen, and T. G. Unterman, “Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in regulating 14-3-3 binding, transactivation and nuclear targetting,” Biochemical Journal, vol. 354, part 3, pp. 605–612, 2001. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Aoki, H. Jiang, and P. K. Vogt, “Proteasomal degradation of the FoxO1 transcriptional regulator in cells transformed by the P3k and Akt oncoproteins,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 37, pp. 13613–13617, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. H. Huang, K. M. Regan, F. Wang et al., “Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 5, pp. 1649–1654, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. H. Matsuzaki, H. Daitoku, M. Hatta, K. Tanaka, and A. Fukamizu, “Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 20, pp. 11285–11290, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. H. Daitoku, M. Hatta, H. Matsuzaki et al., “Silent information regulator 2 potentiates Foxo 1-mediated transcription through its deacetylase activity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 27, pp. 10042–10047, 2004. View at Publisher · View at Google Scholar · View at Scopus
  48. H. Matsuzaki, H. Daitoku, M. Hatta, H. Aoyama, K. Yoshimochi, and A. Fukamizu, “Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 32, pp. 11278–11283, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. L. Qiang, A. S. Banks, and D. Accili, “Uncoupling of acetylation from phosphorylation regulates FoxO1 function independent of its subcellular localization,” Journal of Biological Chemistry, vol. 285, no. 35, pp. 27396–27401, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. D. Frescas, L. Valenti, and D. Accili, “Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes,” Journal of Biological Chemistry, vol. 280, no. 21, pp. 20589–20595, 2005. View at Publisher · View at Google Scholar · View at Scopus
  51. J. M. Park, T. H. Kim, J. S. Bae, M. Y. Kim, K. S. Kim, and Y. H. Ahn, “Role of resveratrol in FOXO1-mediated gluconeogenic gene expression in the liver,” Biochemical and Biophysical Research Communications, vol. 403, no. 3-4, pp. 329–334, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. R. J. Copeland, J. W. Bullen, and G. W. Hart, “Cross-talk between GlcNAcylation and phosphorylation: roles in insulin resistance and glucose toxicity,” American Journal of Physiology—Endocrinology and Metabolism, vol. 295, no. 1, pp. E17–E28, 2008. View at Publisher · View at Google Scholar
  53. M. Kuo, V. Zilberfarb, N. Gangneux, N. Christeff, and T. Issad, “O-glycosylation of FoxO1 increases its transcriptional activity towards the glucose 6-phosphatase gene,” FEBS Letters, vol. 582, no. 5, pp. 829–834, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Kuo, V. Zilberfarb, N. Gangneux, N. Christeff, and T. Issad, “O-GlcNAc modification of FoxO1 increases its transcriptional activity: a role in the glucotoxicity phenomenon?” Biochimie, vol. 90, no. 5, pp. 679–685, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. M. P. Housley, J. T. Rodgers, N. D. Udeshi et al., “O-GlcNAc regulates FoxO activation in response to glucose,” Journal of Biological Chemistry, vol. 283, no. 24, pp. 16283–16292, 2008. View at Publisher · View at Google Scholar · View at Scopus
  56. M. P. Housley, N. D. Udeshi, J. T. Rodgers et al., “A PGC-1α-O-GlcNAc transferase complex regulates FoxO transcription factor activity in response to glucose,” Journal of Biological Chemistry, vol. 284, no. 8, pp. 5148–5157, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Herzig, F. Long, U. S. Jhala et al., “CREB regulates hepatic gluconeogenesis through the coactivator PGC-1,” Nature, vol. 413, no. 6852, pp. 179–183, 2001. View at Publisher · View at Google Scholar · View at Scopus
  58. G. A. Gonzalez and M. R. Montminy, “Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133,” Cell, vol. 59, no. 4, pp. 675–680, 1989. View at Google Scholar · View at Scopus
  59. P. K. Dash, K. A. Karl, M. A. Colicos, R. Prywes, and E. R. Kandel, “cAMP response element-binding protein is activated by Ca2+/calmodulin- as well as cAMP-dependent protein kinase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 11, pp. 5061–5065, 1991. View at Google Scholar · View at Scopus
  60. M. Hagiwara, P. Brindle, A. Harootunian et al., “Coupling of hormonal stimulation and transcription via the cyclic AMP- responsive factor CREB is rate limited by nuclear entry of protein kinase A,” Molecular and Cellular Biology, vol. 13, no. 8, pp. 4852–4859, 1993. View at Google Scholar · View at Scopus
  61. J. C. Chrivia, R. P. S. Kwok, N. Lamb, M. Hagiwara, M. R. Montminy, and R. H. Goodman, “Phosphorylated CREB binds specifically to the nuclear protein CBP,” Nature, vol. 365, no. 6449, pp. 855–859, 1993. View at Publisher · View at Google Scholar · View at Scopus
  62. A. J. Bannister and T. Kouzarides, “The CBP co-activator is a histone acetyltransferase,” Nature, vol. 384, no. 6610, pp. 641–643, 1996. View at Publisher · View at Google Scholar · View at Scopus
  63. V. V. Ogryzko, R. L. Schiltz, V. Russanova, B. H. Howard, and Y. Nakatani, “The transcriptional coactivators p300 and CBP are histone acetyltransferases,” Cell, vol. 87, no. 5, pp. 953–959, 1996. View at Publisher · View at Google Scholar · View at Scopus
  64. T. K. Kim, T. H. Kim, and T. Maniatis, “Efficient recruitment of TFIIB and CBP-RNA polymerase II holoenzyme by an interferon-β enhanceosome in vitro,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 21, pp. 12191–12196, 1998. View at Publisher · View at Google Scholar · View at Scopus
  65. B. L. Kee, J. Arias, and M. R. Montminy, “Adaptor-mediated recruitment of RNA polymerase II to a signal-dependent activator,” Journal of Biological Chemistry, vol. 271, no. 5, pp. 2373–2375, 1996. View at Publisher · View at Google Scholar · View at Scopus
  66. P. Sun, H. Enslen, P. S. Myung, and R. A. Maurer, “Differential activation of CREB by Ca2+/calmodulin-dependent protein kinases type II and type IV involves phosphorylation of a site that negatively regulates activity,” Genes and Development, vol. 8, no. 21, pp. 2527–2539, 1994. View at Google Scholar · View at Scopus
  67. D. Parker, U. S. Jhala, I. Radhakrishnan et al., “Analysis of an activator: coactivator complex reveals an essential role for secondary structure in transcriptional activation,” Molecular Cell, vol. 2, no. 3, pp. 353–359, 1998. View at Google Scholar · View at Scopus
  68. Y. Shi, S. L. Venkataraman, G. E. Dodson, A. M. Mabb, S. LeBlanc, and R. S. Tibbetts, “Direct regulation of CREB transcriptional activity by ATM in response to genotoxic stress,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 16, pp. 5898–5903, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. N. P. Shanware, A. T. Trinh, L. M. Williams, and R. S. Tibbetts, “Coregulated ataxia telangiectasia-mutated and casein kinase sites modulate cAMP-response element-binding protein-coactivator interactions in response to DNA damage,” Journal of Biological Chemistry, vol. 282, no. 9, pp. 6283–6291, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. V. Iourgenko, W. Zhang, C. Mickanin et al., “Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 21, pp. 12147–12152, 2003. View at Publisher · View at Google Scholar · View at Scopus
  71. M. D. Conkright, G. Canettieri, R. Screaton et al., “TORCs: transducers of regulated CREB activity,” Molecular Cell, vol. 12, no. 2, pp. 413–423, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. S. H. Koo, L. Flechner, L. Qi et al., “The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism,” Nature, vol. 437, no. 7062, pp. 1109–1111, 2005. View at Publisher · View at Google Scholar · View at Scopus
  73. Y. Wang, H. Inoue, K. Ravnskjaer et al., “Targeted disruption of the CREB coactivator Crtc2 increases insulin sensitivity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 7, pp. 3087–3092, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. R. Dentin, S. Hedrick, J. Xie, J. Yates III, and M. Montminy, “Hepatic glucose sensing via the CREB coactivator CRTC2,” Science, vol. 319, no. 5868, pp. 1402–1405, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. F. Diraison, P. H. Moulin, and M. Beylot, “Contribution of hepatic de novo lipogenesis and reesterification of plasma non esterified fatty acids to plasma triglyceride synthesis during non-alcoholic fatty liver disease,” Diabetes and Metabolism, vol. 29, no. 5, pp. 478–485, 2003. View at Google Scholar · View at Scopus
  76. F. Diraison and M. Beylot, “Role of human liver lipogenesis and reesterification in triglycerides secretion and in FFA reesterification,” American Journal of Physiology—Endocrinology and Metabolism, vol. 274, no. 2, part 1, pp. E321–E327, 1998. View at Google Scholar · View at Scopus
  77. R. Dentin, J. Girard, and C. Postic, “Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver,” Biochimie, vol. 87, no. 1, pp. 81–86, 2005. View at Publisher · View at Google Scholar · View at Scopus
  78. M. S. Brown and J. L. Goldstein, “Cholesterol feedback: from Schoenheimer's bottle to Scap's MELADL,” Journal of Lipid Research, vol. 50, pp. S15–S27, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. C. M. Taniguchi, T. Kondo, M. Sajan et al., “Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKCλ/ζ,” Cell Metabolism, vol. 3, no. 5, pp. 343–353, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. K. F. Leavens, R. M. Easton, G. I. Shulman, S. F. Previs, and M. J. Birnbaum, “Akt2 is required for hepatic lipid accumulation in models of insulin resistance,” Cell Metabolism, vol. 10, no. 5, pp. 405–418, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Sundqvist, M. T. Bengoechea-Alonso, X. Ye et al., “Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7),” Cell Metabolism, vol. 1, no. 6, pp. 379–391, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. M. T. Bengoechea-Alonso and J. Ericsson, “A phosphorylation cascade controls the degradation of active SREBP1,” Journal of Biological Chemistry, vol. 284, no. 9, pp. 5885–5895, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. G. Roth, J. Kotzka, L. Kremer et al., “MAP kinases Erk1/2 phosphorylate sterol regulatory element-binding protein (SREBP)-1a at serine 117 in vitro,” Journal of Biological Chemistry, vol. 275, no. 43, pp. 33302–33307, 2000. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Lu and J. Y. J. Shyy, “Sterol regulatory element-binding protein 1 is negatively modulated by PKA phosphorylation,” American Journal of Physiology—Cell Physiology, vol. 290, no. 6, pp. C1477–C1486, 2006. View at Publisher · View at Google Scholar · View at Scopus
  85. C. R. Yellaturu, X. Deng, L. M. Cagen et al., “Posttranslational processing of SREBP-1 in rat hepatocytes is regulated by insulin and cAMP,” Biochemical and Biophysical Research Communications, vol. 332, no. 1, pp. 174–180, 2005. View at Publisher · View at Google Scholar · View at Scopus
  86. Y. S. Yoon, W. Y. Seo, M. W. Lee, S. T. Kim, and S. H. Koo, “Salt-inducible kinase regulates hepatic lipogenesis by controlling SREBP-1c phosphorylation,” Journal of Biological Chemistry, vol. 284, no. 16, pp. 10446–10452, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. Y. Hirano, S. Murata, K. Tanaka, M. Shimizu, and R. Sato, “Sterol regulatory element-binding proteins are negatively regulated through SUMO-1 modification independent of the ubiquitin/26 S proteasome pathway,” Journal of Biological Chemistry, vol. 278, no. 19, pp. 16809–16819, 2003. View at Publisher · View at Google Scholar · View at Scopus
  88. V. Giandomenico, M. Simonsson, E. Grönroos, and J. Ericsson, “Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors,” Molecular and Cellular Biology, vol. 23, no. 7, pp. 2587–2599, 2003. View at Publisher · View at Google Scholar · View at Scopus
  89. B. Ponugoti, D. H. Kim, Z. Xiao et al., “SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism,” Journal of Biological Chemistry, vol. 285, no. 44, pp. 33959–33970, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. C. Postic, R. Dentin, P. D. Denechaud, and J. Girard, “ChREBP, a transcriptional regulator of glucose and lipid metabolism,” Annual Review of Nutrition, vol. 27, pp. 179–192, 2007. View at Publisher · View at Google Scholar · View at Scopus
  91. H. C. Towle, E. N. Kaytor, and H. M. Shih, “Regulation of the expression of lipogenic enzyme genes by carbohydrate,” Annual Review of Nutrition, vol. 17, pp. 405–433, 1997. View at Publisher · View at Google Scholar · View at Scopus
  92. T. Kawaguchi, M. Takenoshita, T. Kabashima, and K. Uyeda, “Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 24, pp. 13710–13715, 2001. View at Publisher · View at Google Scholar · View at Scopus
  93. T. Kawaguchi, K. Osatomi, H. Yamashita, T. Kabashima, and K. Uyeda, “Mechanism for fatty acid “sparing” effect on glucose-induced transcription: regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase,” Journal of Biological Chemistry, vol. 277, no. 6, pp. 3829–3835, 2002. View at Publisher · View at Google Scholar · View at Scopus
  94. T. Kabashima, T. Kawaguchi, B. E. Wadzinski, and K. Uyeda, “Xylulose 5-phosphate mediates glucose-induced lipogenesis by xylulose 5-phosphate-activated protein phosphatase in rat liver,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 9, pp. 5107–5112, 2003. View at Publisher · View at Google Scholar · View at Scopus
  95. M. V. Li, B. Chang, M. Imamura, N. Poungvarin, and L. Chan, “Glucose-dependent transcriptional regulation by an evolutionarily conserved glucose-sensing module,” Diabetes, vol. 55, no. 5, pp. 1179–1189, 2006. View at Publisher · View at Google Scholar · View at Scopus
  96. N. G. Tsatsos and H. C. Towle, “Glucose activation of ChREBP in hepatocytes occurs via a two-step mechanism,” Biochemical and Biophysical Research Communications, vol. 340, no. 2, pp. 449–456, 2006. View at Publisher · View at Google Scholar · View at Scopus
  97. C. Guinez, G. Filhoulaud, F. Rayah-Benhamed et al., “O-GlcNAcylation increases ChREBP protein content and transcriptional activity in the liver,” Diabetes, vol. 60, no. 5, pp. 1399–1413, 2011. View at Publisher · View at Google Scholar
  98. M. Prentki and C. J. Nolan, “Islet β cell failure in type 2 diabetes,” Journal of Clinical Investigation, vol. 116, no. 7, pp. 1802–1812, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. T. Kitamura and Y. I. Kitamura, “Role of FoxO proteins in pancreatic β cells,” Endocrine Journal, vol. 54, no. 4, pp. 507–515, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. J. Buteau and D. Accili, “Regulation of pancreatic β-cell function by the forkhead protein FoxO1,” Diabetes, Obesity and Metabolism, vol. 9, supplement 2, pp. 140–146, 2007. View at Publisher · View at Google Scholar
  101. T. Kitamura, J. Nakae, Y. Kitamura et al., “The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth,” Journal of Clinical Investigation, vol. 110, no. 12, pp. 1839–1847, 2002. View at Publisher · View at Google Scholar · View at Scopus
  102. J. Nakae, W. H. Biggs III, T. Kitamura et al., “Regulation of insulin action and pancreatic β-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1,” Nature Genetics, vol. 32, no. 2, pp. 245–253, 2002. View at Publisher · View at Google Scholar · View at Scopus
  103. M. E. Cerf, “Transcription factors regulating β-cell function,” European Journal of Endocrinology, vol. 155, no. 5, pp. 671–679, 2006. View at Publisher · View at Google Scholar
  104. D. Kawamori, H. Kaneto, Y. Nakatani et al., “The forkhead transcription factor Foxo1 bridges the JNK pathway and the transcription factor PDX-1 through its intracellular translocation,” Journal of Biological Chemistry, vol. 281, no. 2, pp. 1091–1098, 2006. View at Publisher · View at Google Scholar · View at Scopus
  105. D. Kawamori, Y. Kajimoto, H. Kaneto et al., “Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH2-terminal kinase,” Diabetes, vol. 52, no. 12, pp. 2896–2904, 2003. View at Publisher · View at Google Scholar · View at Scopus
  106. K. A. Moynihan, A. A. Grimm, M. M. Plueger et al., “Increased dosage of mammalian Sir2 in pancreatic β cells enhances glucose-stimulated insulin secretion in mice,” Cell Metabolism, vol. 2, no. 2, pp. 105–117, 2005. View at Publisher · View at Google Scholar · View at Scopus
  107. Y. I. Kitamura, T. Kitamura, J. P. Kruse et al., “FoxO1 protects against pancreatic β cell failure through NeuroD and MafA induction,” Cell Metabolism, vol. 2, no. 3, pp. 153–163, 2005. View at Publisher · View at Google Scholar · View at Scopus
  108. Y. Gao, J. I. Miyazaki, and G. W. Hart, “The transcription factor PDX-1 is post-translationally modified by O-linked N-acetylglucosamine and this modification is correlated with its DNA binding activity and insulin secretion in min6 β-cells,” Archives of Biochemistry and Biophysics, vol. 415, no. 2, pp. 155–163, 2003. View at Publisher · View at Google Scholar
  109. S. S. Andrali, Q. Qian, and S. Özcan, “Glucose mediates the translocation of neuroD1 by O-linked glycosylation,” Journal of Biological Chemistry, vol. 282, no. 21, pp. 15589–15596, 2007. View at Publisher · View at Google Scholar · View at Scopus
  110. Y. Akimoto, G. W. Hart, L. Wells et al., “Elevation of the post-translational modification of proteins by O-linked N-acetylglucosamine leads to deterioration of the glucose-stimulated insulin secretion in the pancreas of diabetic Goto-Kakizaki rats,” Glycobiology, vol. 17, no. 2, pp. 127–140, 2007. View at Publisher · View at Google Scholar · View at Scopus
  111. J. H. Chae, G. H. Stein, and J. E. Lee, “NeuroD: the predicted and the suprising,” Molecules and Cells, vol. 18, no. 3, pp. 271–288, 2004. View at Google Scholar · View at Scopus
  112. H. Kaneto, T. A. Matsuoka, Y. Nakatani, D. Kawamori, M. Matsuhisa, and Y. Yamasaki, “Oxidative stress and the JNK pathway in diabetes,” Current diabetes reviews, vol. 1, no. 1, pp. 65–72, 2005. View at Publisher · View at Google Scholar · View at Scopus
  113. W. M. Macfarlane, S. B. Smith, R. F. L. James et al., “The p38/reactivating kinase mitogen-activated protein kinase cascade mediates the activation of the transcription factor insulin upstream factor 1 and insulin gene transcription by high glucose in pancreatic β-cells,” Journal of Biological Chemistry, vol. 272, no. 33, pp. 20936–20944, 1997. View at Publisher · View at Google Scholar · View at Scopus
  114. W. M. Macfarlane, C. M. McKinnon, Z. A. Felton-Edkins, H. Cragg, R. F. L. James, and K. Docherty, “Glucose stimulates translocation of the homeodomain transcription factor PDX1 from the cytoplasm to the nucleus in pancreatic β-cells,” Journal of Biological Chemistry, vol. 274, no. 2, pp. 1011–1016, 1999. View at Publisher · View at Google Scholar · View at Scopus
  115. I. Rafiq, G. da Silva Xavier, S. Hooper, and G. A. Rutter, “Glucose-stimulated preproinsulin gene expression and nuclear translocation of pancreatic duodenum homeobox-1 require activation of phosphatidylinositol 3-kinase but not p38 MAPK/SAPK2,” Journal of Biological Chemistry, vol. 275, no. 21, pp. 15977–15984, 2000. View at Publisher · View at Google Scholar · View at Scopus
  116. A. Kishi, T. Nakamura, Y. Nishio, H. Maegawa, and A. Kashiwagi, “Sumoylation of Pdx1 is associated with its nuclear localization and insulin gene activation,” American Journal of Physiology—Endocrinology and Metabolism, vol. 284, no. 4, pp. E830–E840, 2003. View at Google Scholar
  117. M. J. Boucher, L. Selander, L. Carlsson, and H. Edlund, “Phosphorylation marks IPF1/PDX1 protein for degradation by glycogen synthase kinase 3-dependent mechanisms,” Journal of Biological Chemistry, vol. 281, no. 10, pp. 6395–6403, 2006. View at Publisher · View at Google Scholar · View at Scopus
  118. D. Cai, M. Yuan, D. F. Frantz et al., “Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB,” Nature Medicine, vol. 11, no. 2, pp. 183–190, 2005. View at Publisher · View at Google Scholar · View at Scopus
  119. M. Y. Donath and S. E. Shoelson, “Type 2 diabetes as an inflammatory disease,” Nature Reviews Immunology, vol. 11, no. 2, pp. 98–107, 2011. View at Publisher · View at Google Scholar
  120. N. Hosogai, A. Fukuhara, K. Oshima et al., “Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation,” Diabetes, vol. 56, no. 4, pp. 901–911, 2007. View at Publisher · View at Google Scholar · View at Scopus
  121. J. Ye, Z. Gao, J. Yin, and Q. He, “Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice,” American Journal of Physiology—Endocrinology and Metabolism, vol. 293, no. 4, pp. E1118–E1128, 2007. View at Publisher · View at Google Scholar
  122. S. P. Weisberg, D. McCann, M. Desai, M. Rosenbaum, R. L. Leibel, and A. W. Ferrante Jr., “Obesity is associated with macrophage accumulation in adipose tissue,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1796–1808, 2003. View at Publisher · View at Google Scholar · View at Scopus
  123. H. Xu, G. T. Barnes, Q. Yang et al., “Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1821–1830, 2003. View at Publisher · View at Google Scholar · View at Scopus
  124. C. N. Lumeng, J. L. Bodzin, and A. R. Saltiel, “Obesity induces a phenotypic switch in adipose tissue macrophage polarization,” Journal of Clinical Investigation, vol. 117, no. 1, pp. 175–184, 2007. View at Publisher · View at Google Scholar · View at Scopus
  125. C. N. Lumeng, S. M. DeYoung, J. L. Bodzin, and A. R. Saltiel, “Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity,” Diabetes, vol. 56, no. 1, pp. 16–23, 2007. View at Publisher · View at Google Scholar · View at Scopus
  126. S. Fernández-Veledo, I. Nieto-Vazquez, R. Vila-Bedmar, L. Garcia-Guerra, M. Alonso-Chamorro, and M. Lorenzo, “Molecular mechanisms involved in obesity-associated insulin resistance: therapeutical approach,” Archives of Physiology and Biochemistry, vol. 115, no. 4, pp. 227–239, 2009. View at Publisher · View at Google Scholar
  127. H. Kanda, S. Tateya, Y. Tamori et al., “MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity,” Journal of Clinical Investigation, vol. 116, no. 6, pp. 1494–1505, 2006. View at Publisher · View at Google Scholar · View at Scopus
  128. S. Schenk, M. Saberi, and J. M. Olefsky, “Insulin sensitivity: modulation by nutrients and inflammation,” Journal of Clinical Investigation, vol. 118, no. 9, pp. 2992–3002, 2008. View at Publisher · View at Google Scholar · View at Scopus
  129. S. E. Shoelson, L. Herrero, and A. Naaz, “Obesity, inflammation, and insulin resistance,” Gastroenterology, vol. 132, no. 6, pp. 2169–2180, 2007. View at Publisher · View at Google Scholar · View at Scopus
  130. N. D. Perkins, “Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway,” Oncogene, vol. 25, no. 51, pp. 6717–6730, 2006. View at Publisher · View at Google Scholar · View at Scopus
  131. L. F. Chen, W. Fischle, E. Verdin, and W. C. Greene, “Duration of nuclear NF-κB action regulated by reversible acetylation,” Science, vol. 293, no. 5535, pp. 1653–1657, 2001. View at Publisher · View at Google Scholar · View at Scopus
  132. F. Yeung, J. E. Hoberg, C. S. Ramsey et al., “Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase,” EMBO Journal, vol. 23, no. 12, pp. 2369–2380, 2004. View at Publisher · View at Google Scholar · View at Scopus
  133. W. V. Berghe, K. de Bosscher, E. Boone, S. Plaisance, and G. Haegeman, “The nuclear factor-κB engages CBP/p300 and histone acetyltransferase activity for transcriptional activation of the interleukin-6 gene promoter,” Journal of Biological Chemistry, vol. 274, no. 45, pp. 32091–32098, 1999. View at Publisher · View at Google Scholar · View at Scopus
  134. T. Yoshizaki, J. C. Milne, T. Imamura et al., “SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes,” Molecular and Cellular Biology, vol. 29, no. 5, pp. 1363–1374, 2009. View at Publisher · View at Google Scholar · View at Scopus
  135. F. Liang, S. Kume, and D. Koya, “SIRT1 and insulin resistance,” Nature Reviews Endocrinology, vol. 5, no. 7, pp. 367–373, 2009. View at Publisher · View at Google Scholar · View at Scopus
  136. R. Kiernan, V. Brès, R. W. M. Ng et al., “Post-activation turn-off of NF-κB-dependent transcription is regulated by acetylation of p65,” Journal of Biological Chemistry, vol. 278, no. 4, pp. 2758–2766, 2003. View at Publisher · View at Google Scholar · View at Scopus
  137. M. L. Schmitz, I. Mattioli, H. Buss, and M. Kracht, “NF-κB: a multifaceted transcription factor regulated at several levels,” ChemBioChem, vol. 5, no. 10, pp. 1348–1358, 2004. View at Publisher · View at Google Scholar · View at Scopus
  138. L. Vermeulen, G. de Wilde, P. van Damme, W. V. Berghe, and G. Haegeman, “Transcriptional activation of the NF-κB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1),” EMBO Journal, vol. 22, no. 6, pp. 1313–1324, 2003. View at Publisher · View at Google Scholar · View at Scopus
  139. A. Duran, M. T. Diaz-Meco, and J. Moscat, “Essential role of RelA Ser311 phosphorylation by ζPKC in NF-κB transcriptional activation,” EMBO Journal, vol. 22, no. 15, pp. 3910–3918, 2003. View at Publisher · View at Google Scholar · View at Scopus
  140. H. Sakurai, H. Chiba, H. Miyoshi, T. Sugita, and W. Toriumi, “IκB kinases phosphorylate NF-κB p65 subunit on serine 536 in the transactivation domain,” Journal of Biological Chemistry, vol. 274, no. 43, pp. 30353–30356, 1999. View at Publisher · View at Google Scholar · View at Scopus
  141. D. Wang, S. D. Westerheide, J. L. Hanson, and A. S. Baldwin Jr., “Tumor necrosis factor α-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II,” Journal of Biological Chemistry, vol. 275, no. 42, pp. 32592–32597, 2000. View at Google Scholar
  142. F. Fujita, Y. Taniguchi, T. Kato et al., “Identification of NAP1, a regulatory subunit of IκB kinase-related kinases that potentiates NF-κB signaling,” Molecular and Cellular Biology, vol. 23, no. 21, pp. 7780–7793, 2003. View at Publisher · View at Google Scholar · View at Scopus
  143. A. Ryo, F. Suizu, Y. Yoshida et al., “Regulation of NF-κB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA,” Molecular Cell, vol. 12, no. 6, pp. 1413–1426, 2003. View at Publisher · View at Google Scholar · View at Scopus
  144. Y. Fan, R. Mao, Y. Zhao et al., “Tumor necrosis factor-α induces RelA degradation via ubiquitination at lysine 195 to prevent excessive nuclear factor-κB activation,” Journal of Biological Chemistry, vol. 284, no. 43, pp. 29290–29297, 2009. View at Publisher · View at Google Scholar · View at Scopus
  145. P. Delmotte, S. Degroote, J. J. Lafitte, G. Lamblin, J. M. Perini, and P. Roussel, “Tumor necrosis factor α increases the expression of glycosyltransferases and sulfotransferases responsible for the biosynthesis of sialylated and/or sulfated Lewis x epitopes in the human bronchial mucosa,” Journal of Biological Chemistry, vol. 277, no. 1, pp. 424–431, 2002. View at Publisher · View at Google Scholar · View at Scopus
  146. L. R. James, D. Tang, A. Ingram et al., “Flux through the hexosamine pathway is a determinant of nuclear factor κB-dependent promoter activation,” Diabetes, vol. 51, no. 4, pp. 1146–1156, 2002. View at Google Scholar · View at Scopus
  147. H. Y. Won, Y. P. Sang, W. N. Hyung et al., “NFκB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 45, pp. 17345–17350, 2008. View at Publisher · View at Google Scholar · View at Scopus
  148. J. M. Olefsky and C. K. Glass, “Macrophages, inflammation, and insulin resistance,” Annual Review of Physiology, vol. 72, pp. 219–246, 2010. View at Google Scholar
  149. M. Roden, T. B. Price, G. Perseghin et al., “Mechanism of free fatty acid-induced insulin resistance in humans,” Journal of Clinical Investigation, vol. 97, no. 12, pp. 2859–2865, 1996. View at Google Scholar · View at Scopus
  150. G. Boden, “Role of fatty acids in the pathogenesis of insulin resistance and NIDDM,” Diabetes, vol. 46, no. 1, pp. 3–10, 1997. View at Google Scholar · View at Scopus
  151. G. Boden, X. Chen, J. Ruiz, J. V. White, and L. Rossetti, “Mechanisms of fatty acid-induced inhibition of glucose uptake,” Journal of Clinical Investigation, vol. 93, no. 6, pp. 2438–2446, 1994. View at Google Scholar · View at Scopus
  152. A. Dresner, D. Laurent, M. Marcucci et al., “Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity,” Journal of Clinical Investigation, vol. 103, no. 2, pp. 253–259, 1999. View at Google Scholar · View at Scopus
  153. D. E. Kelley and L. J. Mandarino, “Fuel selection in human skeletal muscle in insulin resistance: a reexamination,” Diabetes, vol. 49, no. 5, pp. 677–683, 2000. View at Google Scholar · View at Scopus
  154. S. I. Itani, N. B. Ruderman, F. Schmieder, and G. Boden, “Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκB-α,” Diabetes, vol. 51, no. 7, pp. 2005–2011, 2002. View at Google Scholar · View at Scopus
  155. K. F. Petersen, S. Dufour, D. Befroy, R. Garcia, and G. I. Shulman, “Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes,” The New England Journal of Medicine, vol. 350, no. 7, pp. 664–671, 2004. View at Publisher · View at Google Scholar · View at Scopus
  156. J. K. Kim, Y. J. Kim, J. J. Fillmore et al., “Prevention of fat-induced insulin resistance by salicylate,” Journal of Clinical Investigation, vol. 108, no. 3, pp. 437–446, 2001. View at Publisher · View at Google Scholar · View at Scopus
  157. M. Yuan, N. Konstantopoulos, J. Lee et al., “Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ,” Science, vol. 293, no. 5535, pp. 1673–1677, 2001. View at Publisher · View at Google Scholar · View at Scopus
  158. N. Houstis, E. D. Rosen, and E. S. Lander, “Reactive oxygen species have a causal role in multiple forms of insulin resistance,” Nature, vol. 440, no. 7086, pp. 944–948, 2006. View at Publisher · View at Google Scholar · View at Scopus
  159. J. Hirosumi, G. Tuncman, L. Chang et al., “A central, role for JNK in obesity and insulin resistance,” Nature, vol. 420, no. 6913, pp. 333–336, 2002. View at Publisher · View at Google Scholar · View at Scopus
  160. L. J. C. van Loon and B. H. Goodpaster, “Increased intramuscular lipid storage in the insulin-resistant and endurance-trained state,” Pflugers Archiv, vol. 451, no. 5, pp. 606–616, 2006. View at Publisher · View at Google Scholar · View at Scopus
  161. E. D. Rosen, P. Sarraf, A. E. Troy et al., “PPARγ is required for the differentiation of adipose tissue in vivo and in vitro,” Molecular Cell, vol. 4, no. 4, pp. 611–617, 1999. View at Publisher · View at Google Scholar · View at Scopus
  162. R. Siersbæk, R. Nielsen, and S. Mandrup, “PPARγ in adipocyte differentiation and metabolism—novel insights from genome-wide studies,” FEBS Letters, vol. 584, no. 15, pp. 3242–3249, 2010. View at Publisher · View at Google Scholar
  163. Q. Q. Tang and M. D. Lane, “Activation and centromeric localization of CCAAT/enhancer-binding proteins during the mitotic clonal expansion of adipocyte differentiation,” Genes and Development, vol. 13, no. 17, pp. 2231–2241, 1999. View at Publisher · View at Google Scholar · View at Scopus
  164. O. A. MacDougald and M. D. Lane, “Transcriptional regulation of gene expression during adipocyte differentiation,” Annual Review of Biochemistry, vol. 64, pp. 345–373, 1995. View at Google Scholar · View at Scopus
  165. Z. Wu, E. D. Rosen, R. Brun et al., “Cross-regulation of C/EBPα and PPARγ controls the transcriptional pathway of adipogenesis and insulin sensitivity,” Molecular Cell, vol. 3, no. 2, pp. 151–158, 1999. View at Publisher · View at Google Scholar
  166. E. D. Rosen, C. H. Hsu, X. Wang et al., “C/EBPα induces adipogenesis through PPARγ: a unified pathway,” Genes and Development, vol. 16, no. 1, pp. 22–26, 2002. View at Publisher · View at Google Scholar · View at Scopus
  167. E. Hu, J. B. Kim, P. Sarraf, and B. M. Spiegelman, “Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARγ,” Science, vol. 274, no. 5295, pp. 2100–2103, 1996. View at Publisher · View at Google Scholar · View at Scopus
  168. H. Waki and P. Tontonoz, “Endocrine functions of adipose tissue,” Annual Review of Pathology, vol. 2, pp. 31–56, 2007. View at Publisher · View at Google Scholar · View at Scopus
  169. J. Nakae, T. Kitamura, Y. Kitamura, W. H. Biggs III, K. C. Arden, and D. Accili, “The forkhead transcription factor Foxo1 regulates adipocyte differentiation,” Developmental Cell, vol. 4, no. 1, pp. 119–129, 2003. View at Publisher · View at Google Scholar · View at Scopus
  170. L. Qiao and J. Shao, “SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer- binding protein α transcriptional complex,” Journal of Biological Chemistry, vol. 281, no. 52, pp. 39915–39924, 2006. View at Publisher · View at Google Scholar · View at Scopus
  171. T. Kadowaki, T. Yamauchi, N. Kubota, K. Hara, K. Ueki, and K. Tobe, “Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome,” Journal of Clinical Investigation, vol. 116, no. 7, pp. 1784–1792, 2006. View at Publisher · View at Google Scholar · View at Scopus
  172. I. Wierstra, “Sp1: emerging roles-beyond constitutive activation of TATA-less housekeeping genes,” Biochemical and Biophysical Research Communications, vol. 372, no. 1, pp. 1–13, 2008. View at Publisher · View at Google Scholar
  173. S. P. Jackson and R. Tjian, “O-glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation,” Cell, vol. 55, no. 1, pp. 125–133, 1988. View at Google Scholar · View at Scopus
  174. J. E. Kudlow, “Post-translational modification by O-GlcNAc: another way to change protein function,” Journal of Cellular Biochemistry, vol. 98, no. 5, pp. 1062–1075, 2006. View at Publisher · View at Google Scholar · View at Scopus
  175. M. J. Moreno-Aliaga, M. M. Swarbrick, S. Lorente-Cebrián, K. L. Stanhope, P. J. Havel, and J. A. Martínez, “Sp1-mediated trancription is involved in the metabolism induction of leptin by insulin-stimulated glucose metabolism,” Journal of Molecular Endocrinology, vol. 38, no. 5-6, pp. 537–546, 2007. View at Publisher · View at Google Scholar
  176. P. Zhang, E. S. Klenk, M. A. Lazzaro, L. B. Williams, and R. V. Considine, “Hexosamines regulate leptin production in 3T3-L1 adipocytes through transcriptional mechanisms,” Endocrinology, vol. 143, no. 1, pp. 99–106, 2002. View at Publisher · View at Google Scholar · View at Scopus
  177. A. La Cava and G. Matarese, “The weight of leptin in immunity,” Nature Reviews Immunology, vol. 4, no. 5, pp. 371–379, 2004. View at Google Scholar · View at Scopus
  178. F. H. Einstein, G. Atzmon, X. M. Yang et al., “Differential responses of visceral and subcutaneous fat depots to nutrients,” Diabetes, vol. 54, no. 3, pp. 672–678, 2005. View at Publisher · View at Google Scholar · View at Scopus
  179. S. S. Chung, H. H. Choi, Y. M. Cho, H. K. Lee, and K. S. Park, “Sp1 mediates repression of the resistin gene by PPARγ agonists in 3T3-L1 adipocytes,” Biochemical and Biophysical Research Communications, vol. 348, no. 1, pp. 253–258, 2006. View at Publisher · View at Google Scholar
  180. F. H. Einstein, S. Fishman, J. Bauman et al., “Enhanced activation of a “nutrient-sensing” pathway with age contributes to insulin resistance,” FASEB Journal, vol. 22, no. 10, pp. 3450–3457, 2008. View at Publisher · View at Google Scholar · View at Scopus
  181. R. K. Hall, T. Yamasaki, T. Kucera, M. Waltner-Law, R. O'Brien, and D. K. Granner, “Regulation of phosphoenolpyruvate carboxykinase and insulin-like growth factor-binding protein-1 gene expression by insulin. The role of winged helix/forkhead proteins,” Journal of Biological Chemistry, vol. 275, no. 39, pp. 30169–30175, 2000. View at Google Scholar · View at Scopus
  182. R. Sato, A. Okamoto, J. Inoue et al., “Transcriptional regulation of the ATP citrate-lyase gene by sterol regulatory element-binding proteins,” Journal of Biological Chemistry, vol. 275, no. 17, pp. 12497–12502, 2000. View at Publisher · View at Google Scholar · View at Scopus
  183. Y. A. Moon, J. J. Lee, S. W. Park, Y. H. Ahn, and K. S. Kim, “The roles of sterol regulatory element-binding proteins in the transactivation of the rat ATP citrate-lyase promoter,” Journal of Biological Chemistry, vol. 275, no. 39, pp. 30280–30286, 2000. View at Google Scholar · View at Scopus
  184. M. M. Magaña, S. S. Lin, K. A. Dooley, and T. F. Osborne, “Sterol regulation of acetyl coenzyme A carboxylase promoter requires two interdependent binding sites for sterol regulatory element binding proteins,” Journal of Lipid Research, vol. 38, no. 8, pp. 1630–1638, 1997. View at Google Scholar · View at Scopus
  185. S. Y. Oh, S. K. Park, J. W. Kim, Y. H. Ahn, S. W. Park, and K. S. Kim, “Acetyl-CoA carboxylase β gene is regulated by sterol regulatory element-binding protein-1 in liver,” Journal of Biological Chemistry, vol. 278, no. 31, pp. 28410–28417, 2003. View at Publisher · View at Google Scholar · View at Scopus
  186. M. K. Bennett, J. M. Lopez, H. B. Sanchez, and T. F. Osborne, “Sterol regulation of fatty acid synthase promoter. Coordinate feedback regulation of two major lipid pathways,” Journal of Biological Chemistry, vol. 270, no. 43, pp. 25578–25583, 1995. View at Publisher · View at Google Scholar · View at Scopus
  187. D. E. Tabor, J. B. Kim, B. M. Spiegelman, and P. A. Edwards, “Identification of conserved cis-elements and transcription factors required for sterol-regulated transcription of stearoyl-CoA desaturase 1 and 2,” Journal of Biological Chemistry, vol. 274, no. 29, pp. 20603–20610, 1999. View at Publisher · View at Google Scholar · View at Scopus
  188. S. Kumadaki, T. Matsuzaka, T. Kato et al., “Mouse Elovl-6 promoter is an SREBP target,” Biochemical and Biophysical Research Communications, vol. 368, no. 2, pp. 261–266, 2008. View at Publisher · View at Google Scholar
  189. H. M. Shih, Z. Liu, and H. C. Towle, “Two CACGTG motifs with proper spacing dictate the carbohydrate regulation of hepatic gene transcription,” Journal of Biological Chemistry, vol. 270, no. 37, pp. 21991–21997, 1995. View at Publisher · View at Google Scholar · View at Scopus
  190. B. L. O'Callaghan, S. H. Koo, Y. Wu, H. C. Freake, and H. C. Towle, “Glucose regulation of the acetyl-CoA carboxylase promoter PI in rat hepatocytes,” Journal of Biological Chemistry, vol. 276, no. 19, pp. 16033–16039, 2001. View at Publisher · View at Google Scholar · View at Scopus
  191. C. Rufo, M. Teran-Garcia, M. T. Nakamura, S. H. Koo, H. C. Towle, and S. D. Clarke, “Involvement of a unique carbohydrate-responsive factor in the glucose regulation of rat liver fatty-acid synthase gene transcription,” Journal of Biological Chemistry, vol. 276, no. 24, pp. 21969–21975, 2001. View at Publisher · View at Google Scholar · View at Scopus
  192. R. Beyaert, Nuclear Factor kB: Regulation and Role in Disease, Kluwer Academic Publishers, Dordrecht, The Netherlands, 2003.
  193. O. Muraoka, T. Kaisho, M. Tanabe, and T. Hirano, “Transcriptional activation of the interleukin-6 gene by HTLV-1 p40tax through an NF-κB-like binding site,” Immunology Letters, vol. 37, no. 2-3, pp. 159–165, 1993. View at Publisher · View at Google Scholar · View at Scopus
  194. T. Martin, P. M. Cardarelli, G. C. N. Parry, K. A. Felts, and R. R. Cobb, “Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-κB and AP-1,” European Journal of Immunology, vol. 27, no. 5, pp. 1091–1097, 1997. View at Google Scholar · View at Scopus
  195. S. Bi, O. Gavrilova, D. W. Gong, M. M. Mason, and M. Reitman, “Identification of a placental enhancer for the human leptin gene,” Journal of Biological Chemistry, vol. 272, no. 48, pp. 30583–30588, 1997. View at Publisher · View at Google Scholar · View at Scopus
  196. H. Osawa, K. Yamada, H. Onuma et al., “The G/G genotype of a resistin single-nucleotide polymorphism at -420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3,” American Journal of Human Genetics, vol. 75, no. 4, pp. 678–686, 2004. View at Publisher · View at Google Scholar · View at Scopus