Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic gluconeogenesis

Yoon, Young-Sil;Ryu, Dong-Ryeol;Lee, Min-Woo;Hong, Sung-Pyo;Koo, Seung-Hoi

  • Published : 20090800
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Abstract

During fasting periods, hepatic glucose production is enhanced by glucagon to provide fuels for other organs. This process is mediated via cAMP-dependent induction of the CREB regulated transcriptional coactivator (CRTC) 2, a critical transcriptional activator for hepatic gluconeogenesis. We have previously shown that CRTC2 activity is regulated by AMP activated protein kinase (AMPK) family members. Here we show that adiponectin and thiazolidinedione directly regulate AMPK to modulate CRTC2 activity in hepatocytes. Adiponectin or thiazolidinedione lowered glucose production from primary hepatocytes. Treatment of both reagents reduced gluconeogenic gene expression as well as cAMP-mediated induction of CRE reporter, suggesting that these reagents directly affect CREB/CRTC2- dependent transcription. Furthermore, adiponectin or thiazolidinedione mediated repression of CRE activity is largely blunted by co-expression of phosphorylation defective mutant CRTC2, underscoring the importance of serine 171 residue of this factor. Taken together, we propose that adiponectin and thiazolidinedione promote the modulation of AMPK-dependent CRTC2 activity to influence hepatic gluconeogenesis.

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References

  1. Arias J, Alberts AS, Brindle P, Claret FX, Smeal T, Karin M, Feramisco J, Montminy M. Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature 1994;370:226-9 https://doi.org/10.1038/370226a0
  2. Chrivia JC, Kwok RP, Lamb N, Hagiwar M, Montminy MR, Goodman RH. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 1993;365:855-9 https://doi.org/10.1038/365855a0
  3. Dentin R, Liu Y, Koo SH, Hedrick S, Vargas T, Heredia J, Yates J 3rd, Montminy M. Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2. Nature 2007;449: 366-9 https://doi.org/10.1038/nature06128
  4. Dentin R, Hedrick S, Xie J, Yates J 3rd, Montminy M. Hepatic glucose sensing via the CREB coactivator CRTC2. Science 2008;319:1402-5 https://doi.org/10.1126/science.1151363
  5. Foretz M, Ancellin N, Andreelli F, Saintillan Y, Grondin P, Kahn A, Thorens B, Vaulont S, Viollet B. Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes 2005;54:1331-9 https://doi.org/10.2337/diabetes.54.5.1331
  6. Hall RK, Granner DK. Insulin regulates expression of metabolic genes through divergent signaling pathways. J Basic Clin Physiol Pharmacol 1999;10:119-33
  7. Hanson RW, Reshef L. Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression. Annu Rev Biochem 1997;66:581-611 https://doi.org/10.1146/annurev.biochem.66.1.581
  8. He W, Barak Y, Hevener A, Olson P, Liao D, Le J, Nelson M, Ong E, Olefsky JM, Evans RM. Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle. Proc Natl Acad Sci U S A 2003;100:15712-7 https://doi.org/10.1073/pnas.2536828100
  9. Herzig S, Long F, Jhala US, Hedrick S, Quinn R, Bauer A, Rudolph D, Schutz G, Yoon C, Puigserver P, Spiegelman B, Montminy M. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 2001;413:179-83 https://doi.org/10.1038/35093131
  10. Herzig S, Hedrick S, Morantte I, Koo SH, Galimi F, Montminy M. CREB controls hepatic lipid metabolism through nuclear hormone receptor PPAR-gamma. Nature 2003;426:190-3 https://doi.org/10.1038/nature02110
  11. Koo SH, Satoh H, Herzig S, Lee CH, Hedrick S, Kulkarni R, Evans RM, Olefsky J, Montminy M. PGC-1 promotes insulin resistance in liver through PPAR-alpha-dependent induction of TRB-3. Nat Med 2004;10:530-4 https://doi.org/10.1038/nm1044
  12. Koo SH, Flechner L, Qi L, Zhang X, Screaton RA, Jeffries S., Hedrick S, Xu W, Boussouar F, Brindle P, Takemori H, Montminy M. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 2005;437:1109-11 https://doi.org/10.1038/nature03967
  13. Lebrasseur NK, Kelly M, Tsao TS, Farmer SR, Saha AK, Ruderman NB, Tomas E. Thiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian tissues. Am J Physiol Endocrinol Metab 2006;291:E175-81 https://doi.org/10.1152/ajpendo.00453.2005
  14. Lee EH, Allen PD. Homo-dimerization of RyR1 C-terminus via charged residues in random coils or in an alpha-helix. Exp Mol Med 2007;39:594-602 https://doi.org/10.1038/emm.2007.65
  15. Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, Milne J, Meyers DJ, Cole P, Yates J 3rd, Olefsky J, Guarente L, Montminy M. A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature 2008;456:269-73 https://doi.org/10.1038/nature07349
  16. Nawrocki AR, Rajala MW, Tomas E, Pajvani UB, Saha AK, Trumbauer ME, Pang Z, Chen AS, Ruderman NB, Chen H, Rossetti L, Scherer PE. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 2006;281:2654-60 https://doi.org/10.1074/jbc.M505311200
  17. Screaton RA, Conkright MD, Katoh Y, Best JL, Canettieri G, Jeffries S, Guzman E, Niessen S, Yates JR 3rd, Takemori H, Okamoto M, Montminy M. The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell 2004;119:61-74 https://doi.org/10.1016/j.cell.2004.09.015
  18. Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, Montminy M, Cantley LC. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 2005;310:1642-6 https://doi.org/10.1126/science.1120781
  19. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001;108:1167-74 https://doi.org/10.1172/JCI13505

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