Activation balance of nuclear receptors ERα and CAR regulates hepatic lipid metabolism

• Project/Area Number: 20580318
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: YAMAMOTO Yukio Tokyo Medical and Dental University, 難治疾患研究所, 特任講師 (40321707)
• Co-Investigator(Kenkyū-buntansha): 亀井 康富 東京医科歯科大学, 難治疾患研究所, 准教授 (70300829)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: エストロゲン / エストロゲンレセプター / 脂質代謝 / 核内受容体 / クロストーク / 転写調節 / 生活習慣病 / CAR

Research Abstract

The underlying molecular mechanism of the sex difference in lipid metabolism remains largely unknown. We investigate the roles of hepatic nuclear receptors : ERα (Estrogen Receptor α), which is an authentic estrogen receptor, and LXR (Liver X Receptor) and CAR(Constitutive Androstane/Active Receptor), which are regulators of hepatic lipid metabolism. The transcriptional crosstalk between LXR, CAR, and ERα may explain the suppression mechanism of lipid synthesis by estrogens.

Research Products

• [Journal Article] Nuclear receptor CAR represses TNFa-Induced cell death by interacting with the anti-apoptotic GADD45B. (2010)
  • Author(s): Yamamoto Y, Moore R, Flavell RA, Lu B, Negishi M.
  • Journal Title: PLoS One 5
  • Peer Reviewed
• [Journal Article] Nuclear receptor CAR represses TNFa-Induced cell death by interacting with the anti-apoptotic GADD45B (2010)
  • Author(s): Y.Yamamoto, et al.
  • Journal Title: PLoS One Volume: 5
  • Peer Reviewed
• [Journal Article] The anti-apoptotic factor GADD45B regulates the nuclear receptor CAR-mediated transcription. (2008)
  • Author(s): Yamamoto Y, Negishi M.
  • Journal Title: Drug Metab Dispos. 36 Pages: 1189-1193
  • Peer Reviewed
• [Journal Article] In vivo and in vitro inhibition of monocyte adhesion to endothelial cells and endothelial adhesion molecules by eicosapentaenoic acid. (2008)
  • Author(s): Yamada H, Yoshida M, Nakano Y, Suganami T, Satoh N, Mita T, Azuma K, Itoh M, Yamamoto Y, Kamei Y, Horie M, Watada H, Ogawa Y.
  • Journal Title: Arterioscler Thromb Vasc Biol. 28 Pages: 2173-2179
  • Peer Reviewed
• [Journal Article] The anti-apoptot ic factor GADD45B regulates the nuc1 earreceptor CAR-mediated transcript ion (2008)
  • Author(s): Y. Yamamoto, et al.
  • Journal Title: Drug Metab Di spos. 36 Pages: 1189-1193
  • Peer Reviewed
• [Journal Article] In vivo and in vitro inhibition of monocyte adhes ion toendothelial cells and endothelial adhes ion molecules by eicosapentaenoic acid (2008)
  • Author(s): H. Yamada, et al.
  • Journal Title: Arterioscler Thromb Vase Biol. 28 Pages: 2173-2179
  • Peer Reviewed
• [Presentation] Estrogen Receptor a Mediates 17a-Ethynylestradiol-Causing Hepatotoxicity (2008)
  • Author(s): 山本幸男
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] 核内受容体CAR の活性化は肝臓癌を誘発する (2008)
  • Author(s): Yukio Yamamoto, Masahiko Negishi
  • Organizer: 第145回日本獣医学会
  • Place of Presentation: 日麻布大学
• [Presentation] Estrogen Receptor α(ERα)の活性化は肝内胆汁うっ滞を引き起こす (2008)
  • Author(s): Yukio Yamamoto, Rick Moore, Frank Gonzalez, Kenneth Korach, Masahiko Negishi
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド
• [Remarks] ホームページ等