The role and mechanisms of Fgf21 as the metabolic regulator in white adipose tissue

• Project/Area Number: 23790111
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: KONISHI Morichika 神戸薬科大学, 薬学部, 准教授 (00322165)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Fgf / 白色脂肪組織 / ケトン食 / 糖代謝 / インスリン抵抗性 / Fgf21 / FGF21 / インスリン感受性 / ケトン体 / ノックアウト / 糖新生

Research Abstract

A low-carbohydrate, high-fat ketogenic diet (KD) induces hepatic ketogenesis and is believed to affect energy metabolism in mice. As hepatic Fgf21 expression was markedly induced in mice fed KD, we examined the effects of KD feeding on metabolism and the roles of Fgf21 in metabolism in mice fed KD using Fgf21 knockout mice. The present findings indicate that KD feeding impairs insulin sensitivity in mice due to insulin resistance in white adipose tissue. In addition, our findings indicate that Fgf21 induced to express by KD is a negative regulator of adipocyte insulin sensitivity in adaptation to a low-carbohydrate malnutritional state.

Research Products

• [Journal Article] Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine. (2013)
  • Author(s): Kim KH, Jeong YT, Oh H, Kim SH, Cho JM, Kim YN, Kim SS, Kim do H, Hur KY, Kim HK, Ko T, Han J, Kim HL, Kim J, Back SH, Komatsu M, Chen H, Chan DC, Konishi M, Itoh N, Choi CS, Lee MS.
  • Journal Title: Nature Medicine Volume: 19 Issue: 1 Pages: 83-92
  • DOI: 10.1038/nm.3014
  • Peer Reviewed
• [Journal Article] Soluble β-glucan from Grifola frondosa induces proliferation and Dectin-1/Syk signaling in resident macrophages via the GM-CSF autocrine pathway (2012)
  • Author(s): Masuda Y, Togo T, Mizuno M, Konishi M, Nanba H
  • Journal Title: Journal of Leukocyte Biology Volume: 91 Issue: 4 Pages: 547-556
  • DOI: 10.1189/jlb.0711386
  • Peer Reviewed
• [Journal Article] Functions of MAPR (membrane-associated progesterone receptor) family members as heme/steroid-binding proteins. (2012)
  • Author(s): Kimura I, Nakayama Y, Konishi M, Terasawa K, Ohta M, Itoh N, Fujimoto M.
  • Journal Title: Current Protein & Peptide Science Volume: 13 Pages: 687-696
  • NAID: 120005466669
  • Peer Reviewed
• [Journal Article] FGF10 and FGF21 as regulators in adipocytes development and metabolism. (2011)
  • Author(s): Ohta H, K on i sh i M, Itoh N
  • Journal Title: Endocrine, Metabolic and Immune Disorders-Drug Targets Volume: 11 Pages: 302-309
• [Journal Article] Time-imposed daily restricted feeding induces rhythmic expression of Fgf21 in white adipose tissue (2011)
  • Author(s): K. Oishi, M. Konishi, Y. Murata, N. Itoh
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 412 Issue: 2 Pages: 302-309
  • DOI: 10.1016/j.bbrc.2011.07.125
  • Peer Reviewed
• [Journal Article] Growth hormone induces hepatic production of fibroblast growth factor 21 through a mechanism dependent on lipolysis in adipocytes. (2011)
  • Author(s): Chen W, Hoo RL, Konishi M, Itoh N, LeeP, Ye H, Lam KSL, Xu A
  • Journal Title: J. Biol. Chem. Volume: 286 Issue: 40 Pages: 34559-34566
  • DOI: 10.1074/jbc.m111.285965
  • Peer Reviewed
• [Journal Article] FGF10 and FGF21 as regulators in adipocyte development and metabolism. (2011)
  • Author(s): Ohta H, Konishi M, Itoh N
  • Journal Title: Endocrine‚ Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune‚ Endocrine & Metabolic Disorders) Volume: 11 Issue: 4 Pages: 302-309
  • DOI: 10.2174/187153011797881166
  • Peer Reviewed
• [Presentation] Fgf21は低炭水化物高脂質食負荷時にインスリン抵抗性を惹起する。 (2012)
  • Author(s): 西尾 恭史，村田 雄亮，小西 守周，伊藤 信行
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: マリンメッセ福岡
• [Presentation] Fgf21 は低炭水化物高脂質食負荷時に 白色脂肪組織においてインスリン抵抗性 を惹起する (2011)
  • Author(s): 嶋田 将也,村田 雄亮,中村 尋俊,黒川直樹, 小 西 守周伊藤 信行
  • Organizer: BMB2011
• [Presentation] 高脂肪低炭水化物食負荷時のFgf21 の生理的役割 (2011)
  • Author(s): 小西守周、村田雄亮、嶋田将也、黒川直樹、増田有紀、伊藤信行
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 淡路夢舞台国際会議場
• [Presentation] Fgf21の胸線内CD8^+T細胞の分化、成熟における役割
  • Author(s): 増田有紀,筒井沙耶,神田由紀子,太田紘也,小西守周,伊藤信行
  • Organizer: 第35回日本分子生物学会年会
• [Presentation] Fgf21は低炭水化物高脂質食負荷時にインスリン抵抗性を惹起する。
  • Author(s): 西尾恭史,村田雄亮,小西守周伊藤信行
  • Organizer: 第35回日本分子生物学会年会
• [Presentation] 高脂肪低炭水化物食負荷時のFgf21の生理的役割
  • Author(s): 小西守周,村田雄亮,嶋田将也,黒川直樹,増田有紀,伊藤信行
  • Organizer: 第32回日本肥満学会
• [Book] 遺伝子医学MOOK 20号 ナノバイオ技術と最新創薬応用研究 (2012)
  • Author(s): 小西守周、伊藤信行
  • Total Pages: 5
  • Publisher: メディカルドゥ
• [Book] FGFおよびFGF受容体とその機能の多様性について (2012)
  • Author(s): 小西守周、太田紘也、伊藤信行
  • Total Pages: 5
  • Publisher: 学研メディカル秀潤社