Role of TFAP2B as environment response gene on Metabolic Syndrome

• Project/Area Number: 21591129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: MAEGAWA Hiroshi 滋賀医科大学, 医学部, 教授 (00209363)
• Co-Investigator(Renkei-kenkyūsha): MAEDA Shiro 理化学研究所, 遺伝子多型研究センター, チームリーダー (50314159)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: メタボリックシンドローム / 肥満 / 脂肪組織 / 転写因子 / AP2B / アディポサイトカイン / 遺伝子改変マウス / AP-2β / PKCμ / MCP-1 / Adiponectin / IL-6 / TNFα / アディポネクチン / レプチン / 皮下脂肪組織 / 内臓脂肪組織 / TFAP2B

Research Abstract

TFAP2B(AP-2β) is a candidate gene for conferring susceptibility to obesity and type 2 diabetes. We also found that protein kinase C(PKC)μwas highly phosphorylated in the re-feeding condition. Furthermore, overexpression of PKCμenhanced the effects of AP-2βon the expression of these adipocytokines. We also found that overexpression of AP-2βin 3T3-L1 adiposities impaired the promoter activity of IRS-1, and subsequently decreased mRNA and protein expression. Theses findings suggested that postprandial activation of PKCμplays roles in disordered postprandial adipocytokine expression and impaired insulin signaling through AP-2β.

Research Products

• [Journal Article] Regulation of Mitochondrial Biogenesis by Lipoprotein Lipase in Muscle of Insulin Resistant Offspring of Parents with Type 2 Diabetes (2012)
  • Author(s): Morino K, Petersen KF, Sono S, Choi CS, Varman T. Samuel VT, Lin A, Gallo A, Zhao H, Kashiwagi A, Ira J. Goldberg IR, Wang H, , Robert H. Eckel RH, Maegawa H, and Shulman GI
  • Journal Title: Diabetes Volume: 61 Pages: 877-87
  • Peer Reviewed
• [Journal Article] Autophagy regulates inflammation in adipocytes (2012)
  • Author(s): YoshizakiT, Kusunoki C, Kondo M, Yasuda M, Kume S, Morino K, Sekine O, Ugi S, Uzu T, Nishio Y, Kashiwagi A, Maegawa H.
  • Journal Title: Biochem Biophys Res Commun Volume: 417 Pages: 352-7
  • Peer Reviewed
• [Journal Article] Regulation of Mitochondrial Biogenesis by Lipoprotein Lipase in Muscle of Insulin-Resistant Offspring of Parents With Type 2 Diabetes (2012)
  • Author(s): Morino K, Maegawa H, et al
  • Journal Title: Diabetes Volume: 61 Issue: 4 Pages: 877-87
  • DOI: 10.2337/db11-1391
  • Peer Reviewed
• [Journal Article] Autophagy regulates inflammation in adipocytes (2012)
  • Author(s): Yoshizaki T, Maegawa H., et al
  • Journal Title: Biochem Biophys Res Commun Volume: 417 Issue: 1 Pages: 352-357
  • DOI: 10.1016/j.bbrc.2011.11.114
  • Peer Reviewed
• [Journal Article] Postprandial activation of protein kinase Cμregulates the expression of adipocytokines via the transcription factor AP-2β (2011)
  • Author(s): Kondo M, Ugi S, Morino K, Fuke T, Obata T, Yoshizaki T, Nishio Y, Maeda S, Kashiwagi A, Maegawa H.
  • Journal Title: Int J Mol Med Volume: 28 Pages: 95-100
  • Peer Reviewed
• [Journal Article] Postprandial activation of protein kinase Cμ regulates the expression of adipocytokines via the transcription factor AP-2ss (2011)
  • Author(s): Kondo M, Maegawa H, et al
  • Journal Title: Int J Mol Med. Volume: 28 Pages: 95-100
  • DOI: 10.3892/ijmm.2011.651
  • Peer Reviewed
• [Journal Article] Postprandial activation of protein kinase CM regulates the expression of adipocytokines via the transcription factor AP-2β. (2011)
  • Author(s): Kondo M, Maegawa, et al
  • Journal Title: Int J Mol Med. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Association between serum soluble TNFα receptors and renal dysfunction in type 2 diabetic patients without proteinuria. (2011)
  • Author(s): Miyazawa I, Maegawa H., et al.
  • Journal Title: Diab Research Clin Pract Volume: (in press)
  • Peer Reviewed
• [Journal Article] Transcription factor AP-2β: a negative regulator of IRS-1 gene expression (2010)
  • Author(s): Meng X, Kondo M, Morino K, Fuke T, Obata T, Yoshizaki, Ugi S, Nishio Y, Maeda S, Araki E, Kashiwagi A, Maegawa H.
  • Journal Title: Biochem Biophys Res Commun Volume: 392 Pages: 526-532
  • Peer Reviewed
• [Journal Article] Transcription factor AP-2βinhibits expression and secretion of leptin, an insulin-sensitizing hormone, in 3T3-L1 adipocytes (2010)
  • Author(s): Fuke T, Yoshizaki T, Kondo M, Morino K, Obata T, Ugi S, Nishio Y, Maeda S, Kashiwagi A, Maegawa H.
  • Journal Title: Int J of Obesity Volume: 34 Pages: 670-678
  • Peer Reviewed
• [Journal Article] Relation of the expression of transcriptional factor TFAP2B to that of adipokines in subcutaneous and omental adipose tissues (2010)
  • Author(s): Ugi S, Nishio Y, Yamamoto H, Ikeda K, 5 KobayashiM, Tsukada S Kondo S, Morino K, Obata T, Yoshizaki T, Uzu T, Naitoh H, Tani T, Maeda S, Kashiwagi A, and Maegawa H.
  • Journal Title: Obesity Volume: 18 Pages: 1277-82
  • Peer Reviewed
• [Journal Article] Transcription factor AP-2□ inhibits expression and secretion of leptin, an insulin-sensitizing hormone, in 3T3-L1 adipocytes (2010)
  • Author(s): Fuke T, Maegawa H, et al.
  • Journal Title: International Journal of Obesity (In press)
  • Peer Reviewed
• [Journal Article] Possible role of transcriptional factor TFAP2B in regulation of adipokine genes in subcutaneous and omental adipose tissues (2010)
  • Author(s): Ugi S, Maegawa H, et al
  • Journal Title: Obesity (In press)
  • Peer Reviewed
• [Journal Article] Transcription factor AP-2β: a negative regulator of IRS-1 gene expression (2010)
  • Author(s): Meng X, Maegawa H, et al.
  • Journal Title: Biochem Biophys Res Commun (In press)
  • Peer Reviewed
• [Presentation] Postprandial Activation of Protein Kinase CμRegulates the Expression of Adipocytokines Via Transcription Factor AP-2β (2011)
  • Author(s): Kondo M, Ugi S, Morino K, Fuke T, Obata T, Yoshizaki T, Nishio Y, Maeda S, Kashiwagi A, Maegawa H.
  • Organizer: The Annual meeting of 71st American Diabetes Association
  • Place of Presentation: San Diego, USA
• [Presentation] The transcription factor AP-2βis a unique regulator of IRS-1 and a candidate gene for insulin resistance (2010)
  • Author(s): Kondo M, Meng X, Morino K, Yoshizaki K, Fuke T, Obata T, Ugi S, Nishio Y, Maeda S, Kashiwagi A, and Maegawa H.
  • Organizer: The Annual meeting of 70th American diabetes association
  • Place of Presentation: Tanpa, USA
• [Presentation] New Role of Protein Kinase Cμon Adipocytokine Expression in Re-Feeding Condition Via Transcription Factor AP-2β, a Regulator of Adipocytokine Expression (2009)
  • Author(s): Kondo M, Maegawa H, Morino K, Yoshizaki T, Fike T, Obata T, Ugi S, Nioshio Y, Maeda S, Kashiwagi A.
  • Organizer: The Annual meeting of 69th American diabetes association
  • Place of Presentation: New Olens USA