Molecular mechanism of adipocyte proliferation and adipose tissue development

• Project/Area Number: 15081204
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: ITOH Nobuyuki Kyoto University, Graduate School of Pharmaceutical Sciences, Professor (10110610)
• Co-Investigator(Kenkyū-buntansha): KONISHI Morichika Kyoto University, Graduate School of Pharmaceutical Sciences, Assistant Professor (00322165)
• Project Period (FY): 2003 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥41,300,000 (Direct Cost: ¥41,300,000); Fiscal Year 2007: ¥7,900,000 (Direct Cost: ¥7,900,000); Fiscal Year 2006: ¥7,900,000 (Direct Cost: ¥7,900,000); Fiscal Year 2005: ¥8,500,000 (Direct Cost: ¥8,500,000); Fiscal Year 2004: ¥8,500,000 (Direct Cost: ¥8,500,000); Fiscal Year 2003: ¥8,500,000 (Direct Cost: ¥8,500,000)
• Keywords: Fibroblast Growth Factor / White Adipose Tissue / Tissue Formation / Differentiation / Cell proliferation / Obesity / 白色脂肪組繊 / 組繊形成 / 細胞分化 / 脂肪組織 / FGF / 脂肪細胞

Research Abstract

Fibroblast Growth factors (Fgfs) are important intercellular signaling molecules. We elucidated the role of FGF signalings in the development of white adipose tissue (WAT). Analyses of Fgf10^<-/-> WAT have indicated that Fgf10 plays crucial roles in the proliferation of preadipocytes and their subsequent differentiation into mature adipocytes at embryonic stages. In addition, we found that Fgf receptor 2c potentially activated by Fgf9 plays a role in the adipocyte hypertrophy in the mesenteric WAT. Fgf21 was reported to be a metabolic regulator with multiple beneficial effects on glucose homeostasis and insulin sensitivity. We generated Fgf21^<-/-> mice to examine the physiological role of Fgf21. Increase in the weight of WAT and decrease in plasma FFA levels were observed in Fgf21^<-/-> mice. Our findings provide a novel insight into the development and function of WAT.

Research Products

• [Journal Article] Role of Fgf receptor 2c in adipocyte hypertrophy in mesenteric white adipose tissue (2008)
  • Author(s): Konishi, M., et al.
  • Journal Title: Molecular and Cellular Endocrinology (In press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Functional evolutionary history of the mouse Fgf gene family (2008)
  • Author(s): Itoh, N., et al.
  • Journal Title: Developmental Dynamics 237 Pages: 18-27
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Role of Fgf receptor 2c in adipocyte hypertrophy in mesenteric white adlpose tissue (2008)
  • Author(s): Konishi, M., et. al.
  • Journal Title: Molecular and Cellular Endocrinology. (In press)
  • Peer Reviewed
• [Journal Article] Functional evolutionary history of the mouse Fgf gene family (2008)
  • Author(s): Itoh, N., et. al.
  • Journal Title: Developmental Dynamics 237 Pages: 18-27
  • Peer Reviewed
• [Journal Article] Brorin, a novel secreted BMP antagonist, promotes neurogenesis in mouse neural precursor cells. (2007)
  • Author(s): Koike, N., et al.
  • Journal Title: Journal of Biological Chemistry 282 Pages: 15843-15850
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Brorin, a novel secreted BMP antagonist, promotes neurogenesis in mouse neural precursor cells (2007)
  • Author(s): Koike, N., et. al.
  • Journal Title: Journal of Biological Chemistry 282 Pages: 15843-15850
  • Peer Reviewed
• [Journal Article] Role of Fgf10 in cell proliferation in white adipose tissue. (2006)
  • Author(s): Konishi, M., et al.
  • Journal Title: Molecular and Cellular Endocrinology 249 Pages: 71-77
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Neudesin, a secreted factor, promotes neural cell proliferation and neuronal differentiation in mouse neural precursor cells. (2006)
  • Author(s): Kimura, I., et al.
  • Journal Title: Journal of Neuroscience Research 83 Pages: 1415-1424
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Role of Fgf10 in cell proliferation in white adipose tissue. (2006)
  • Author(s): Morichika Konishi, Toshiyuki Asaki, Naomi Koike, Hiroyuki Miwa, Ayumi Miyake, Nobuyuki Itoh
  • Journal Title: Molecular and Cellular Endocrinology 249 Pages: 71-77
• [Journal Article] Fgf21 is essential for hematopoiesis in zebrafish (2006)
  • Author(s): Hajime Yamauchi, Yuhei Hotta, Morichika Konishi, Ayumi Miyake, Atsuo Kawahara, Nobuyuki Itoh
  • Journal Title: EMBO Reports 7 Pages: 649-654
• [Journal Article] Neudesin, a secreted factor, promotes neural cell proliferation and neuronal differentiation in mouse neural precursor cells. (2006)
  • Author(s): Ikuo Kimura, Morichika Konishi, Ayumi Miyake, Masafumi Fujimoto, Nobuyuki Itoh
  • Journal Title: Journal of Neuroscience Research 83 Pages: 1415-1424
• [Journal Article] Role of Fgf10 in cell proliferation in white adipose tissue (2006)
  • Author(s): M.Konishi, T.Asaki, N.Koike, H.Miwa, A.Miyake, N.Itoh
  • Journal Title: Molecular and Cellular Endocrinology (印刷中)
• [Journal Article] Regulation of mammalian tooth cusp patterning by ectodin (2005)
  • Author(s): Kassai, Y., et al.
  • Journal Title: Science 309 Pages: 2067-2070
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Neudesin, a novel secreted protein with a unique primary structure and neurotrophic activity (2005)
  • Author(s): Kimura, I., et al.
  • Journal Title: Journal of Neuroscience Research 79 Pages: 287-294
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Fgf19 regulated by Hh signaling is required for zebrafish, forebrain development (2005)
  • Author(s): A.Miyake, Y.Nakayama, M.Konishi, N.Itoh
  • Journal Title: Developmental Biology 288 Pages: 259-275
• [Journal Article] Regulation of mammalian tooth cusp patterning by ectodin (2005)
  • Author(s): Y.Kassai, P.Munne, Y.Hotta, E.Penttila, K.Kavanagh, N.Ohbayashi, S.Takada, I.Thesleff, J.Jernvall, N.Itoh
  • Journal Title: Science 309 Pages: 2067-2070
• [Journal Article] Complementary antagonistic actions between C-type natriureic peptide and the MAPK pathway through FGFR-3 in ATDC cells. (2005)
  • Author(s): A.Ozawa, Y.Omatsu, A.Yasoda, M.Miura, Y.Sakuma, Y.Nakaturu, H.Arai, N.Itoh, K.Nakao
  • Journal Title: Bone 36 Pages: 1056-1064
• [Journal Article] Roles of fibroblast growth factor 10 (Fgf10) in adipogenesis in vivo. (2004)
  • Author(s): Asaki, T., et al.
  • Journal Title: Molecular and Cellular Endocrinology 218 Pages: 119-128
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Evolution of Fgf and Fgfr gene families (2004)
  • Author(s): Itoh, N., et al.
  • Journal Title: Trends in Genetics 20 Pages: 563-569
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Roles of fibroblast growth factor 10 (Fgf1O) in adipogenesis in vivo. (2004)
  • Author(s): Asaki, T., et al.
  • Journal Title: Molecular and Cellular Endocrinology 218 Pages: 116-128
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Roles of fibroblast growth factor 10 (Fgf10) in adipogenesis in vivo (2004)
  • Author(s): T.Asaki et al.
  • Journal Title: Mol.Cell.Endocrinol. 214 Pages: 119-128
• [Journal Article] Evolution of the Fgf and Fgfr gene families (2004)
  • Author(s): N.Itoh, D.M.Ornitz
  • Journal Title: Trends in Genetics 20 Pages: 563-569
• [Journal Article] Characterization of growth factor-binding structures in heparin/heparan sulfate using an octasaccbaride library. (2004)
  • Author(s): S.Ashikari-Hada et al.
  • Journal Title: J.Biol.Chem. 279 Pages: 12346-12354
• [Journal Article] Role of Fgf receptor 2c in adipocyte hypertrophy in mesenteric white adipose tissue
  • Author(s): Konishi, M., et al.
  • Journal Title: Molecular and Cellular Endocrinology (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 腸間膜脂肪組織形成におけるFgf受容体2の役割の解明 (2007)
  • Author(s): 中村尋俊, 他
  • Organizer: BMB2007(第30回日本分子生物学会年会 第80回日本生化学会大会 合同大会)
  • Place of Presentation: パシフイコ横浜
  • Year and Date: 2007-12-13
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Role of Fgf receptor 2c in adipocyte hypertrophy in mesenteric white adipose tissue (2007)
  • Author(s): Nakamura, H., et al.
  • Organizer: BMB2007
  • Place of Presentation: Pacifico Yokohama
  • Year and Date: 2007-12-13
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 腸間腹脂肪組織形成におけるFgf受容体2の役割の解明 (2007)
  • Author(s): 中村 尋俊, 他
  • Organizer: BMB2007 (第30回日本分子生物学会年会 第80回日本生化学会大会 合同大会)
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-13
• [Presentation] 腸間膜脂肪組織形成におけるFgfシグナリングの役割 (2006)
  • Author(s): 小西守周, 他
  • Organizer: 第27回肥満学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2006-10-28
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Role of Fgf signaling in the development of mesenteric white adipose tissue (2006)
  • Author(s): Konishi, M., et al.
  • Organizer: 27^<th> Annual Meeting of Japan Society for the Study of Obesity
  • Place of Presentation: Kobe International Conference Center
  • Year and Date: 2006-10-28
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Fibroblast Growth Factor Receptor 2 is Necessary for Hypertrophy of Mature Adipocytes in Mesenteric White Adipose Tissue (2006)
  • Author(s): Konishi, M., et al
  • Organizer: The 11^<th> Adiposcience Symposium
  • Place of Presentation: 千里阪急ホテル
  • Year and Date: 2006-08-19
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Fibroblast Growth Factor Receptor 2 is Necessary for Hypertrophy of Mature Adipocytes in Mesenteric White Adipose Tissue (2006)
  • Author(s): Konishi, M., et al.
  • Organizer: The 11^<th> Adiposcience Symposium
  • Place of Presentation: Senri Hankyu Hotel
  • Year and Date: 2006-08-19
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Fgf10による脂肪細胞分化、増殖におけるRbファミリーの役割 (2005)
  • Author(s): 小西守周, 他
  • Organizer: 第28回日本分子生物学会年会
  • Place of Presentation: 福岡Yahoo! JAPANドーム
  • Year and Date: 2005-12-09
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Role of pRbs in adipocyte proliferation and differentiation by Fgf10 (2005)
  • Author(s): Konishi, M., et al.
  • Organizer: The 28^<th> Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Fukuoka Yahoo! JAPAN DOME
  • Year and Date: 2005-12-09
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Fgf10による脂肪細胞増殖機構の検討 (2004)
  • Author(s): 小西守周, 他
  • Organizer: 第27回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2004-12-09
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Mechanism of Adipocyte Proliferation by Fgf10 (2004)
  • Author(s): Konishi, M., et al.
  • Organizer: The 27^<th> Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Kobe Port Island
  • Year and Date: 2004-12-09
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Fgf10の脂肪細胞増殖における役割 (2003)
  • Author(s): 小西守周, 他
  • Organizer: 第26回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2003-12-11
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Role of Fgf10 in Adipocyte Proliferation (2003)
  • Author(s): Konishi, M., et al.
  • Organizer: The 26^<th> Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Kobe Port Island
  • Year and Date: 2003-12-11
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] In vivoにおける脂肪細胞分化のメカニズムの解明 (2003)
  • Author(s): 浅木敏之, 他
  • Organizer: 第8回アディポサイエンス研究会シンポジウム
  • Place of Presentation: 千里阪急ホテル
  • Year and Date: 2003-08-09
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Mechanism of adipocyte differentiation in vivo (2003)
  • Author(s): Asaki, T., et al.
  • Organizer: The 8^<th> Adiposcience Symposium
  • Place of Presentation: Senri Hankyu Hotel
  • Year and Date: 2003-08-09
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 糖尿病カレントライブラリー7 脂肪細胞と脂肪組織 (2007)
  • Author(s): 小西守周, 他
  • Publisher: 文光堂
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Tounyoubyou Current Library 7 Adipcytes and Adipose tissue (2007)
  • Author(s): Konishi, M., et al.
  • Publisher: BUNKODO CO., LTD.
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 糖尿病カレントライブラリー7 脂肪細胞と脂肪組織 (2007)
  • Author(s): 小西 守周, 他
  • Publisher: 文光堂
• [Publications] F.Asaki et al.: "Roles of fibroblast growth factor 10 (Fgf10) in adipogenesis in vivo"Mol.Cell.Endocrinol. (印刷中). (2004)
• [Publications] M.Affolter et al.: "Tube or not tube remodelling epithelial tissues by branching morphogenesis"Dev.Cell. 4. 11-18 (2003)
• [Publications] N.Kusu et al.: "Sclerostin is a novel secreted osteoblast-derived bone morhogenetic protein (BP) antagonist"J.Biol.Chem.. 278. 24113-24117 (2003)
• [Publications] R.C.Burns et al.: "Requirement for fibroblast growth factor 10 or fibroblast growth factor receptor 2-IIIb signaling"Dev.Biol. 265. 61-74 (2003)
• [Publications] N.Itoh: "Encyclopaedia of Endocrine Diseases"Fibroblast growth factor (FGF)(印刷中). (2003)