Identification of the mechanism of the development of nonalcoholic fatty liver disease in testosterone deficiency in men

• Project/Area Number: 15K19522
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Senmaru Takafumi 京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (20637889)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: テストステロン低下 / 非アルコール性脂肪肝炎 / モデルマウス / インスリン抵抗性

Outline of Final Research Achievements

Orchiectomized mice fed high-fat diet showed decreased serum testosterone level, increased visceral fat, increased insulin resistance, increased serum inflammatory marker level, and hepatic fibrogenesis. These perturbations in the model mice were normalized to the levels of control mice by testosterone supplementation. Our results suggested that NASH is initiated by addition of chronic inflammation to fatty liver caused by testosterone deficiency and insulin resistance.

Research Products

• [Journal Article] Abnormal lipid/lipoprotein metabolism and high plasma testosterone levels in male but not female aromatase-knockout mice (2017)
  • Author(s): Amano A, Kondo Y, Noda Y, Ohta M, Kawanishi N, Machida S, Mitsuhashi K, Senmaru T, Fukui M, Takaoka O, Mori T, Kitawaki J, Ono M, Saibara T, Obayashi H, Ishigami A.
  • Journal Title: Arch Biochem Biophys Volume: - Pages: 47-58
  • DOI: 10.1016/j.abb.2017.03.007
  • Peer Reviewed / Open Access
• [Journal Article] Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes (2016)
  • Author(s): Mitsuhashi K, Senmaru T, Fukuda T, Yamazaki M, Shinomiya K, Ueno M, Kinoshita S, Kitawaki J, Katsuyama M, Tsujikawa M, Obayashi H, Nakamura N, Fukui M.
  • Journal Title: Endocrine Volume: 51 Issue: 1 Pages: 174-184
  • DOI: 10.1007/s12020-015-0666-y
  • Peer Reviewed
• [Presentation] テストステロン低下と慢性炎症により惹起されるサルコペニアを伴った非アルコール性脂肪肝炎の病態解明 (2015)
  • Author(s): 千丸貴史、濵口真英、福田拓也、木村寿宏、橋本善隆、北川功幸、三橋一輝、田中武兵、浅野麻衣、山真裕、中村直登、福井道明
  • Organizer: 第2回肝臓と糖尿病・代謝研究会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-23
• [Presentation] Testosteroneは3T3-L1脂肪細胞においてGLUT4を介して細胞内糖取込みを促進する (2015)
  • Author(s): 三橋一輝、千丸貴史、福田拓也、辻川宗男、尾林博、山崎真裕、中村直登、福井道明
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21
• [Book] 週間 日本医事新報 差分解説 アンドロゲン低下とインスリン抵抗性 (2015)
  • Author(s): 千丸貴史
  • Total Pages: 1
  • Publisher: 株式会社 日本医事新報社