The functional analysis of TFE3 to the new therapy for metabolic syndrome

• Project/Area Number: 19689019
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: University of Tsukuba
• Principal Investigator: NAKAGAWA Yoshimi University of Tsukuba, 大学院・人間総合科学研究科, 講師 (80361351)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000); Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2008: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2007: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
• Keywords: 生活習慣病 / 遺伝子発現制御 / 転写因子 / エネルギー代謝 / 脂肪分化 / TFE3 / 糖尿病 / インスリン / 糖代謝

Research Abstract

We analyzed what TFE3 functioned in various tissues. TFE3 suppressed adipogenesis and increased thermogenesis in adipose tissue, induced glycogen synthesis in muscle, and upregulated insulin signaling in kidney. We proposed that TFE3 functioned in energy homeostasis in various tissues. Next we will research the therapeutic methods to increase the ability of TFE3.

Research Products

• [Journal Article] Adipocyte-Derived Microvesicles Are Associated with Multiple Angiogenic Factors and Induce Angiogenesis in Vivo and in Vitro. (2010)
  • Author(s): Aoki N, Yokoyama R, Asai N, Ohki M, Ohki Y, Kusubata K, Heissig B, Hattori K, Nakagawa Y, Matsuda T
  • Journal Title: Endocrinology (in press)
  • Peer Reviewed
• [Journal Article] Protein kinase Cbeta mediates hepatic induction of sterol regulatory element-binding protein-1c by insulin. (2010)
  • Author(s): Yamamoto T, Watanabe K, Inoue N, Nakagawa Y, Ishigaki N, Matsuzaka T, Takeuchi Y, Kobayashi K, Yatoh S, Takahashi A, Suzuki H, Yahagi N, Gotoda T, Yamada N, Shimano H
  • Journal Title: J Lipid Res. (in press)
  • Peer Reviewed
• [Journal Article] Polyunsaturated fatty acids selectively suppress sterol regulatory element-binding protein-1 through proteolytic processing and autoloop regulatory circuit. (2010)
  • Author(s): Takeuchi Y, Yahagi N, Izumida Y, Nishi M, Kubota M, Teraoka Y, Yamamoto T, Matsuzaka T, Nakagawa Y, Sekiya M, Iizuka Y, Ohashi K, Osuga JI, Gotoda T, Ishibashi S, Itaka K, Kataoka K, Nagai R, Yamada N, Kadowaki T, Shimano H
  • Journal Title: J Biol Chem. 285(15) Pages: 11681-91
  • Peer Reviewed
• [Journal Article] Protein kinase Cbeta mediates hepatic induction of sterol regulatory element-binding protein-1c by insulin (2010)
  • Author(s): Yamamoto T
  • Journal Title: J Lipid Res (in press)
  • Peer Reviewed
• [Journal Article] The liver-enriched transcription factor CREBH is nutritionally regulated and activated by fatty acids and PPARalpha (2010)
  • Author(s): Danno H
  • Journal Title: Biochem Biophys Res Commun. 391 Pages: 1222-7
  • Peer Reviewed
• [Journal Article] TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. (2009)
  • Author(s): Kato M, Putta S, Wang M, Yuan H, Lanting L, Nair I, Gunn A, Nakagawa Y, Shimano H, Todorov I, Rossi JJ, Natarajan R
  • Journal Title: Nature Cell Biology. 11(7) Pages: 881-9
  • Peer Reviewed
• [Journal Article] TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN (2009)
  • Author(s): Kato M
  • Journal Title: Nat Cell Biol. 11 Pages: 881-9
  • Peer Reviewed
• [Journal Article] The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice (2009)
  • Author(s): Nakanishi N
  • Journal Title: Biochem Biophys Res Commun. 385 Pages: 492-6
  • Peer Reviewed
• [Journal Article] Cholesterol accumulation and diabetes in pancreatic beta-cell-specific SREBP-2 transgenic mice: a new model for lipotoxicity. (2008)
  • Author(s): Ishikawa M, Iwasaki Y, Yatoh S, Kato T, Kumadaki S, Inoue N, Yamamoto T, Matsuzaka T, Nakagawa Y, Yahagi N, Kobayashi K, Takahashi A, Yamada N, Shimano H
  • Journal Title: J Lipid Res. 49(12) Pages: 2524-34
  • Peer Reviewed
• [Journal Article] Palmitate impairs and eicosapentaenoate restores insulin secretion through regulation of SREBP-1c in pancreatic islets. (2008)
  • Author(s): Kato T, Shimano H, Yamamoto T, Ishikawa M, Kumadaki S, Matsuzaka T, Nakagawa Y, Yahagi N, Nakakuki M, Hasty AH, Takeuchi Y, Kobayashi K, Takahashi A, Yatoh S, Suzuki H, Sone H, Yamada N
  • Journal Title: Diabetes 57(9) Pages: 2382-92
  • Peer Reviewed
• [Journal Article] Cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is involved in adipocyte differentiation and hypertrophy, linking to obesity, and insulin resistance. (2008)
  • Author(s): Inoue N, Yahagi N, Yamamoto T, Ishikawa M, Watanabe K, Matsuzaka T, Nakagawa Y, Takeuchi Y, Kobayashi K, Takahashi A, Suzuki H, Hasty AH, Toyoshima H, Yamada N, Shimano H
  • Journal Title: J Biol Chem. 283(30) Pages: 21220-9
  • Peer Reviewed
• [Journal Article] Cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is involved in adipocyte differentiation and hypertrophy, linking to obesity and insulin resistance.. (2008)
  • Author(s): Inoue N, et.al.
  • Journal Title: J Biol Chem. 283 Pages: 21220-9
  • Peer Reviewed
• [Journal Article] Palmitate impairs and eicosapentaenoate restores insulin secretion through regulation of SREBP-lc in pancreatic islets. (2008)
  • Author(s): Kato T, et.al.
  • Journal Title: Diabetes. 57 Pages: 2382-92
  • Peer Reviewed
• [Journal Article] Hormone-sensitive lipase is involved in hepatic cholesterol ester hydrolysis. (2008)
  • Author(s): Sekiya M, et.al.
  • Journal Title: J Lipid Res. 49 Pages: 1829-38
  • Peer Reviewed
• [Journal Article] Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. (2007)
  • Author(s): Matsuzaka T, Shimano H, Yahagi N, Kato T, Atsumi A, Yamamoto T, Inoue N, Ishikawa M, Okada S, Ishigaki N, Iwasaki H, Iwasaki Y, Karasawa T, Kumadaki S, Matsui T, Sekiya M, Ohashi K, Hasty AH, Nakagawa Y, Takahashi A, Suzuki H, Yatoh S, Sone H, Toyoshima H, Osuga J, Yamada N.
  • Journal Title: Nat Med. 13(10) Pages: 1193-202
  • Peer Reviewed
• [Journal Article] Protein kinase A suppresses sterol regulatory element-binding protein-1C expression via phosphorylation of liver X receptor in the liver. (2007)
  • Author(s): Yamamoto T, Shimano H, Inoue N, Nakagawa Y, Matsuzaka T, Takahashi A, Yahagi N, Sone H, Suzuki H, Toyoshima H, Yamada N
  • Journal Title: J Biol Chem. 282(16) Pages: 11687-95
  • Peer Reviewed
• [Journal Article] Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. (2007)
  • Author(s): Matsuzaka T
  • Journal Title: Nature Medicine 13 Pages: 1193-1202
  • Peer Reviewed
• [Journal Article] Protein kinase A suppresses sterol regulatory element-binding protein-1C expression via phosphorylation of liver X receptor in the liver. (2007)
  • Author(s): Yamamoto T
  • Journal Title: JBC 282 Pages: 11687-11695
  • Peer Reviewed
• [Journal Article] Identification and characterization of microvesicles secreted by 3T3-L1 adipocytes: redox- and hormone-dependent induction of milk fat globule-epidermal growth factor 8-associated microvesicles. (2007)
  • Author(s): Aoki N
  • Journal Title: Endocrinology 148 Pages: 3850-3862
  • Peer Reviewed
• [Presentation] Nobuhiro YAMADA CREBH is the new transcription factor for hepatic energy metabolism in fasted state (2010)
  • Author(s): Yoshimi NAKAGAWA, Hitoshi SHIMANO
  • Organizer: 14th international Congress of Endocrinology (ICE2010) Official Satellite Symposia
  • Place of Presentation: Kyoto Japan
  • Year and Date: 2010-03-31
• [Presentation] 脂質代謝調節におけるFGF21を中心とした転写因子クロストークの解明 (2009)
  • Author(s): 中川嘉, 徳重直子, 新行内晶子, 松坂賢, 石井清朗, 浦山修, 山田信博, 島野仁
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] FGF21を制御する転写因子CREBHは生活習慣病を改善する (2009)
  • Author(s): 中川嘉、清水英寿、矢部祥子、島野仁、松坂賢、石井清明、高橋昭光、矢藤繁、鈴木浩明、浦山修、山田信博
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-05-22
• [Presentation] 肝臓特異的発現転写因子CREB-Hの生活習慣病病態の分子メカニズム (2009)
  • Author(s): 中川嘉
  • Organizer: 日本内分泌学会総会
  • Place of Presentation: 前橋
  • Year and Date: 2009-04-24
• [Presentation] 肝臓特異的発現転写因子CREB-Hの生活習慣病病態への機能解析 (2008)
  • Author(s): 中川嘉, 矢部祥子, 島野仁, 浦山修, 山田信博
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] 骨格筋におけるTFE3の機能解析 (2008)
  • Author(s): 岩崎仁, 島野仁, 中川嘉, 松坂賢, 石井清朗, 小林和人, 矢藤繁, 高橋昭光, 鈴木浩明, 山田信博
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] 肝臓におけるエネルギー代謝調節因子TFE3のメタボリックシンドロームへの作用メカニズム (2008)
  • Author(s): 中川嘉
  • Organizer: 日本農芸化学会2008年度会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-03-29
• [Presentation] 肝臓におけるエネルギー代謝調節因子 TFE3 のメタボリックシンドロームへの作用メカニズム (2008)
  • Author(s): 中川嘉
  • Organizer: 日本農芸化学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-03-29
• [Presentation] TFE3による脂肪細胞の分化への影響 (2007)
  • Author(s): 中川嘉、島野仁、岩崎仁、松坂賢、高橋昭光、鈴木浩明、山田信博
  • Organizer: 第50回日本糖尿病学会年次学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-25
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/clinical-med/endocrinology/research/
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  • URL: http://www.md.tsukuba.ac.jp/clinical-med/endocrinology/research/
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  • URL: http://www.md.tsukuba.ac.ib/clinical-med/endocrinology/research/
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  • URL: http://www.md.tsUkuba.ac.jp/basic-med/diag-bia