Elucidation of molecular mechanism of skeletal muscle function, focusing on transcription factors

2010 Fiscal Year Final Research Report

• Project/Area Number: 20580097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied biochemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KAMEI Yasutomi Tokyo Medical and Dental University, 難治疾患研究所, 准教授 (70300829)
• Project Period (FY): 2008 – 2010
• Keywords: 代謝生理

Research Abstract

Skeletal muscle, the largest organ in the human body, plays roles in energy expenditure, glucose uptake and exercise. Here, we show that FOXO1 enhances gene expression of cathepsin L, a lysosomal proteinase, in vivo and in vitro. Our data indicate that cathepsin L is a direct target of FOXO1 in the skeletal muscle and suggest that the FOXO1/cathepsin L pathway plays a role in diabetes and starvation-induced skeletal muscle metabolic change and atrophy. Also, we investigated the glucose metabolism of RXRγ mice with induced obesity and impaired glucose metabolism. The data showed that increased glucose uptake in the skeletal muscle improved systemic glucose metabolism, and increasing RXRγ expression may be a novel therapeutic strategy against impaired glucose metabolism caused by obesity.

Research Products

• [Journal Article] Increased expression of DNA methyltransferase 3a in obese adipose tissue : studies with transgenic mice overexpressing Dnmt3a. (2010)
  • Author(s): Y.Kamei, T.Suganami, S.Kanai, K.Hayashi, Y.Yamamoto, S.Miura, O.Ezaki, M.Okano, Y.Ogawa.
  • Journal Title: Obesity 18 Pages: 314-321
• [Journal Article] The cathepsin L gene is a direct target of FOXO1 in the skeletal muscle. (2010)
  • Author(s): Y.Yamazaki, Y.Kamei, S.Sugita, F.Akaike, S.Kanai, S.Miura, Y.Hirata, B.R.Troen, T.Kitamura, I.Nishino, T.Suganami, O.Ezaki, Y.Ogawa.
  • Journal Title: Biochemical Journal 427(Corresponding author) Pages: 171-178
• [Journal Article] A novel glycerophosphodiester phosphodiesterase GDE5 controls skeletal muscle development via a non-enzymatic mechanism. (2010)
  • Author(s): Y.Okazaki, N.Ohshima, I.Yoshizawa, Y.Kamei, S.Mariggio, K.Okamoto, M.Maeda, Y.Nogusa, Y.Fujioka, T.Izumi, Y.Ogawa, Y.Shiro, M.Wada, N.Kato, D.Corda, N.Yanaka.
  • Journal Title: Journal of Biological Chemistry 285 Pages: 27652-27663
• [Journal Article] Overexpression of FOXO1 in skeletal muscle does not alter longevity in mice. (2009)
  • Author(s): T.Chiba, Y.Kamei, T.Shimizu, T.Shirasawa, A.Katsumata, L.Shiraishi, S.Sugita, Y.Ogawa, S.Miura, O.Ezaki.
  • Journal Title: Mechanisms of Ageing and Development 130 Pages: 420-428
• [Journal Article] AMPK activity is not essential for an increase in fatty acid oxidation during low-intensity exercise. (2009)
  • Author(s): S.Miura, Y.Kai, Y.Kamei, C.Bruce, N.Kubota, M.Febbraio, T.Kadowaki, O.Ezaki.
  • Journal Title: American Journal of Physiology 296 Pages: E47-E55
• [Journal Article] Regulation of SREBP1c gene expression in the skeletal muscle : role of RXR/LXR and FOXO1. (2008)
  • Author(s): Y.Kamei, S.Miura, T.Suganami, F.Akaike, S.Kanai, S.Sugita, A.Katsumata, H.Aburatani, O.Ezaki, Y.Ogawa.
  • Journal Title: Endocrinology 149 Pages: 2293-2305
• [Presentation] 骨格筋受容体における核内受容体RXRの糖代謝促進作用 (2010)
  • Author(s): 杉田聡、亀井康富、赤池史子、菅波孝祥、金井沙綾香、真鍋康子、藤井宣晴、三浦進司、江崎治、小川佳宏
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 群馬
  • Year and Date: 20101001-20101002
• [Presentation] 骨格筋機能と遺伝子発現調節 (2010)
  • Author(s): 亀井康富、小川佳宏
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京
  • Year and Date: 20100327-20100330
• [Presentation] 骨格筋におけるFOXO1によるタンパク分解酵素カテプシンL遺伝子の転写調節 (2009)
  • Author(s): 山崎芳浩、亀井康富、三浦進司、杉田聡、赤池史子、金井紗綾香、平田結喜緒、江崎浩、菅波孝祥、小川佳宏
  • Organizer: 第30回日本肥満学会
  • Place of Presentation: 静岡
  • Year and Date: 20091009-20091010
• [Presentation] 骨格筋におけるSREBP1c遺伝子の発現調節:LXR/RXR/FOXO1の役割 (2008)
  • Author(s): 亀井康富、三浦進司、菅波孝祥、赤池史子、金井紗綾香、杉田聡、勝又阿貴、江崎治、小川佳宏
  • Organizer: 第29回日本肥満学会
  • Place of Presentation: 大分
  • Year and Date: 20081017-20081018
• [Presentation] 骨格筋におけるSREBP1c遺伝子の発現調節:核内受容体LXR/RXRおよびフォークヘッド因子FOXO1の役割 (2008)
  • Author(s): 亀井康富、三浦進司、菅波孝祥、赤池史子、金井紗綾香、杉田聡、勝又阿貴、江崎治、小川佳宏
  • Organizer: 第62回日本栄養食糧学会
  • Place of Presentation: 埼玉
  • Year and Date: 20080502-20080504
• [Remarks] ホームページ等