Ectopic fat accumulation and dysfunction in cultured myocytes-Regulatory role of Sirt1

• Project/Area Number: 24590877
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: The University of Tokyo
• Principal Investigator: ETO Masato 東京大学, 医学部附属病院, 准教授 (80282630)
• Co-Investigator(Kenkyū-buntansha): IIJIMA Katsuya 東京大学, 高齢社会総合研究機構, 准教授 (00334384) ; OTA Hidetaka 東京大学, 医学部附属病院, 助教 (20431869)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 骨格筋 / 脂肪酸 / ビタミンD / 異所性脂肪蓄積 / サルコペニア / 異所性脂肪 / Sirt1

Outline of Final Research Achievements

Sarcopenia and ectopic fat deposition is related to aging and age-associated disorders. Therefore, to develop the efficient therapeutic strategy, the molecular mechanisms need to be clarified. Aim of this project was to examine the mechanisms underlying fatty acid-induced skeletal muscle dysfunction. Treatment with high dose of fatty acids induced lipid droplet formation and apoptosis accompanied with cellular insulin resistance, in C2C12 myocytes. Vitamin D3 induced Sirt-1 upregulation and restoration of fatty acid-induced insulin resistance. Finally, isoproterenol upregulated the expression levels of VDR in C2C12 cells.

Research Products

• [Journal Article] Association of decreased sympathetic nervous activity with mortality of older adults in long-term care. (2014)
  • Author(s): Shibasaki K, Ogawa S, Yamada S, Iijima K, Eto M, Kozaki K, Toba K, Akishita M, Ouchi Y.
  • Journal Title: Geriatr Gerontol Int. Volume: 14 Pages: 159-166
  • Peer Reviewed
• [Journal Article] trans-Resveratrol in Gnetum gnemon protects against oxidative-stress-induced endothelial senescence (2013)
  • Author(s): Ota H, Akishita M, Tani H, Tatefuji T, Ogawa S, Iijima K, Eto M, Shirasawa T, Ouchi Y
  • Journal Title: J Nat Prod Volume: 76 Issue: 7 Pages: 1242-1247
  • DOI: 10.1021/np300841v
  • Peer Reviewed
• [Journal Article] trans-Resveratrol in Gnetum gnemon protects against oxidative-stress-induced endothelial senescence. (2013)
  • Author(s): Ota H, Akishita M, Tani H, Tatefuji T, Ogawa S, Iijima K, Eto M, Shirasawa T, Ouchi Y.
  • Journal Title: J Nat Prod Volume: 26 Pages: 1242-1247
  • Peer Reviewed
• [Journal Article] Src kinase-mediates androgen receptor-dependent non-genomic activation of signaling cascade leading to endothelial nitric oxide synthase. (2012)
  • Author(s): Yu J, Akishita M, Eto M, Koizumi H, Hashimoto R, Ogawa S, Tanaka K, Ouchi Y, Okabe T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 424 Pages: 538-543
  • Peer Reviewed
• [Journal Article] Testosterone deficiency accelerates neuronal and vascular aging of SAMP8 mice: protective role of eNOS and SIRT1. (2012)
  • Author(s): Ota H, Akishita M, Akiyoshi T, Kahyo T, Setou M, Ogawa S, Iijima K, Eto M, Ouchi Y.
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed