Analysis of SIK3, newly regulator of glucose, lipid, cholesterol, and bile acid

• Project/Area Number: 23791048
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Osaka University (2012); 独立行政法人医薬基盤研究所 (2011)
• Principal Investigator: UEBI Tastuya 大阪大学, 大学院・生命機能研究科, 招へい研究員 (80513803)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: メタボリックシンドローム / 肥満 / 脂質代謝 / リン酸化 / コレステロール代謝

Research Abstract

SIK3-KO mice do not get fat, but were caused liver dysfunction. In order to develop the anti-obesity drug, in this study, a function of SIK3 was analyzed. SIK3-KO mice were high sensitive to bile acid, and the high bile acid level induced serious liver dysfunction. By analysis of gene expression level, it was found that SIK-KO mice lost the regulation of expression of gene related to cholesterol and bile acid responding a diet.It was suggested that SIK3 was master regulator of cholesterol and bile acid homeostasis. By mass spectrometry analysis of phosphorylatedproteins, two candidate target proteins of SIK3 were found. Since there was no difference in the fatty acid composition between SIK3-KO and wild type, it was suggested that fatty acid do not relate to energy reflux.

Research Products

• [Journal Article] Involvement of SIK3 in Glucose and Lipid Homeostasis in Mice (2012)
  • Author(s): Uebi T, Itoh Y, Hatano O, Kumagai A, Sanosaka M, Sasaki T, Sasagawa S, Doi J, Tatsumi K, Mitamura K, Morii E, Aozasa K, Kawamura T, Okumura M, Nakae J, et al.
  • Journal Title: PLoS One Volume: 7 Issue: 5 Pages: e37803-e37803
  • DOI: 10.1371/journal.pone.0037803
  • Peer Reviewed
• [Journal Article] SIK3 is essential for chondrocyte hypertrophy during skeletal development in mice. (2012)
  • Author(s): Sasagawa S, Takemori H, Uebi T, Ikegami D, Hiramatsu K, Ikegawa S, Yoshikawa H, Tsumaki N
  • Journal Title: Development Volume: 139(6) Pages: 1153-63
  • Peer Reviewed
• [Journal Article] SIK3 is essential forchondrocyte hypertrophy during skeletaldevelopment in mice (2012)
  • Author(s): Sasagawa,S.,Takemori,H.,Uebi,T.,Ikegami,D.,Hiramatsu,K.,Ikegawa,S.,Yoshikawa,H.and Tsumaki,N.
  • Journal Title: Development Volume: 139巻 Issue: 6 Pages: 1153-1163
  • DOI: 10.1242/dev.072652
  • Peer Reviewed
• [Presentation] SIK3 はコレステロール、胆汁酸代謝の制御因子である (2011)
  • Author(s): 上尾達也、伊東祐美、 熊谷彩子、竹森洋
  • Organizer: 第34回日本分子生物学会大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-16
• [Presentation] SIK3はコレステロール-胆汁酸代謝の制御因子である (2011)
  • Author(s): 上尾達也、伊東祐美、熊谷彩子、竹森洋
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜