Investigation of the mechanisms of hepatic insul in sensitization by retinoi cacid.

• Project/Area Number: 23790819
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: TSUCHIYA Hiroyuki 京都薬科大学, 薬学部, 講師 (00403402)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: レチノイン酸 / タミバロテン / インスリン抵抗性 / レプチン / STAT3 / 肝臓 / NAFLD / NASH / アンチセンスRNA

Research Abstract

Based on our original finding, the leptin-dependent hepatic insulinsensitization by retinoid, I investigated its precise mechanisms. It was demonstrated thatretinoid activates hepatic leptin signaling by directly inducing leptin receptor expressionvia retinoid receptor. A synthetic rtinoid, tamibarotene, also showed the same effect,suggesting its potential as a novel insulin-resistance treatment. Moreover, AntiX wasidentified as a target gene of hepatic leptin signaling, and the expression level of AntiX inthe liver was significantly correlated with the pathological status of insulin resistance.

Research Products

• [Journal Article] High-Fat, High- Fructose Induces Hepatic Iron Overloadvia a Hepcidin-Independent MechanismPrior to the Onset of Liver Steatosis andInsulin Resistance in Mice. (2013)
  • Author(s): H Tsuchiya, et al
  • Journal Title: Metabolism Volume: 62 Pages: 62-69
• [Journal Article] A retinoic acid receptor agonisttamibarotene suppresses ironaccumulation in the liver. (2013)
  • Author(s): O Yoshikawa, Y Ebata, H Tsuchiya, et al.
  • Journal Title: Obesity Volume: 21
• [Journal Article] A retinoic acid receptor agonist tamibarotene suppresses iron accumulation in the liver. (2013)
  • Author(s): Osamu Yoshikawa
  • Journal Title: Obesity Volume: 21 Issue: 1
  • DOI: 10.1002/oby.20013
  • Peer Reviewed
• [Journal Article] High-fat, high-fructose diet induces hepatic iron overload via a hepcidin-independent mechanism prior to the onset of liver steatosis and insulin resistance in mice. (2013)
  • Author(s): Hiroyuki Tsuchiya
  • Journal Title: Metabolism Volume: 62 Issue: 1 Pages: 62-69
  • DOI: 10.1016/j.metabol.2012.06.008
  • Peer Reviewed
• [Journal Article] Retinoids ameliorate insulin resistance in a leptin-dependentmanner in mice. (2012)
  • Author(s): H Tsuchiya, et al.
  • Journal Title: Hepatology Volume: 56 Pages: 1319-1330
• [Journal Article] 非アルコール性脂肪性肝疾患治療薬としてのレチノイドの有用性 (2012)
  • Author(s): 土谷博之
  • Journal Title: 薬学雑誌 Volume: 132 Pages: 903-910
  • NAID: 130001888708
• [Journal Article] Retinoids ameliorate insulin resistance in a leptin-dependent manner in mice. (2012)
  • Author(s): Hiroyuki Tsuchiya
  • Journal Title: Hepatology Volume: 56 Issue: 4 Pages: 1319-1330
  • DOI: 10.1002/hep.25798
  • Peer Reviewed
• [Presentation] 非アルコール性脂肪性肝疾患とレチノイド (2012)
  • Author(s): 土谷博之
  • Organizer: 第62回日本薬学会近畿支部大会
  • Place of Presentation: 西宮(招待講演)
  • Year and Date: 2012-10-20
• [Presentation] レチノイドによるインスリン抵抗性改善作用に関わるSTAT3標的転写産物の網羅的探索 (2012)
  • Author(s): 土谷博之
  • Organizer: 日本レチノイド研究会第23回学術集会
  • Place of Presentation: 日米子
  • Year and Date: 2012-10-19
• [Presentation] Hepatic iron overload induced by a high-fat, high-fructose dietoccurs prior to the onset of liversteatosis and insulin resistance via ahepcidin-independent mechanism inmice (2012)
  • Author(s): H Tsuchiya, et al.
  • Organizer: The 4th EMBO meeting.
  • Place of Presentation: Nice (France)
• [Presentation] 他レチノイドによるインスリン抵抗性改善作用におけるレプチン依存的メカニズムの解明 (2012)
  • Author(s): 土谷博之
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢
• [Presentation] Hepatic iron overload induced by a high-fat, high-fructose diet occurs prior to the onset of liver steatosis and insulin resistance via a hepcidin-independent mechanism in mice. (2012)
  • Author(s): Hiroyuki Tsuchiya
  • Organizer: The 4th EMBO meeting
  • Place of Presentation: Nice, France
• [Presentation] 非アルコール性脂肪性肝疾患とレチノイド (2012)
  • Author(s): 土谷博之
  • Organizer: 第62回日本薬学会近畿支部大会
  • Place of Presentation: 西宮
  • Invited
• [Presentation] レチノイドによるインスリン抵抗性改善作用に関わるSTAT3標的転写産物の網羅的探索 (2012)
  • Author(s): 土谷博之
  • Organizer: 日本レチノイド研究会 第23回学術集会
  • Place of Presentation: 米子
• [Presentation] Retinoids ameliorate insulin resistance in a leptin-dependentmanner (2011)
  • Author(s): H Tsuchiya, et al.
  • Organizer: The 3rd EMBO meeting.
  • Place of Presentation: Vienna
• [Presentation] レチノイドシグナルを介したレプチン依存的インスリン抵抗性改善メカニズムの解析 (2011)
  • Author(s): 土谷博之、江端優、小島千尋、池田義人、勝間陸太郎、濱進、首藤紘一、汐田剛史、小暮健太朗
  • Organizer: 第61会日本薬学会近畿支部大会
  • Place of Presentation: 神戸
• [Presentation] Retinoids ameliorate insulin resistance in a leptin-dependent manner. (2011)
  • Author(s): Hiroyuki Tsuchiya, Yu Ebata, Chihiro Kojima, Yoshito Ikeda, Rikutaro Katsuma, Tomohiko Sakabe, Susumu Hama, Tatsuaki Tsuruyama, Koichi Shudo, Kentaro Kogure, and Goshi Shiota
  • Organizer: The 3rd EMBO meeting
  • Place of Presentation: VIENNA