Studies on molecular mechanisms in differentiation and dedifferentiation of adipocytes.

• Project/Area Number: 26670809
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Hiroshima University
• Principal Investigator: Kanematsu Takashi 広島大学, 医歯薬保健学研究院, 教授 (10264053)
• Co-Investigator(Kenkyū-buntansha): ASANO SATOSHI 広島大学, 大学院医歯薬保健学研究院, 助教 (30570535) ; HARADA KAE 広島大学, 大学院医歯薬保健学研究院, 助教 (60432663) ; YAMAWAKI YOSUKE 広島大学, 大学院医歯薬保健学研究院, 助教 (90584061)
• Research Collaborator: OUE KANA 広島大学病院, 歯科診療医
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脂肪細胞 / 分化 / 脱分化 / エネルギー代謝 / 脂肪代謝 / 白色脂肪細胞 / 褐色脂肪細胞 / 脂肪分化 / 寒冷刺激 / ベージュ細胞

Outline of Final Research Achievements

We produced PLC-related catalytically inactive protein-knockout (Prip-KO) mice. Prip-KO mice showed a lean phenotype. In this study, we examined whether PRIP is involved in adipocyte differentiation and/or dedifferentiation. Adipocyte differentiation was significantly inhibited in Prip-KO mice compared with wild-type mice. However, a feature of adipocyte dedifferentiation was similar between the two genotypes. This study demonstrated that PRIP regulates the process of adipocyte differentiation and hypertrophy. These findings are inspiring a novel therapeutic strategy for obese patients.

Research Products

• [Journal Article] Phospholipase C-related catalytically inactive protein is a new modulator of thermogenesis promoted by β-adrenergic receptors in brown adipocytes (2015)
  • Author(s): Kana Oue, Jun Zhang, Kae Harada-Hada, Satoshi Asano, Yosuke Yamawaki, Masaki Hayashiuchi, Hisako Furusho, Takashi Takata, Masahiro Irifune, Masato Hirata, Takashi Kanematsu
  • Journal Title: Journal of Biological Chemistry Volume: 291 Issue: 8 Pages: 4185-96
  • DOI: 10.1074/jbc.m115.705723
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] New molecular basis in the regulation of lipolysis via dephosphorylation (2015)
  • Author(s): 大植香菜， 原田佳枝， 兼松隆
  • Journal Title: Folia Pharmacologica Japonica Volume: 146 Issue: 2 Pages: 93-97
  • DOI: 10.1254/fpj.146.93
  • NAID: 130005092136
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed / Open Access
• [Journal Article] Phospholipase C-Related Catalytically Inactive Protein (PRIP) regulates lipolysis in adipose tissue by modulating the phosphorylation of hormone-sensitive lipase (2014)
  • Author(s): T. Okumura, K. Harada, K. Oue, J. Zhang, S. Asano, M. Hayashiuchi, A. Mizokami, H. Tanaka, M. Irifune, N. Kamata, M. Hirata, and T. Kanematsu.
  • Journal Title: PLoS One Volume: 9 Issue: 6 Pages: e100559-e100559
  • DOI: 10.1371/journal.pone.0100559
  • Peer Reviewed / Open Access
• [Journal Article] Phospholipase C-related catalytically inactive protein participates in the autophagic elimination of Staphylococcus aureus infecting mouse embryonic fibroblasts. (2014)
  • Author(s): Harada-Hada K, Harada K, Kato F, Hisatsune J, Tanida I, Ogawa M, Asano S, Sugai M, Hirata M, Kanematsu T.
  • Journal Title: PLoS One. Volume: 9 Issue: 5 Pages: e98285-e98285
  • DOI: 10.1371/journal.pone.0098285
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phospholipase C-related catalytically inactive protein (PRIP) controls KIF5B-mediated insulin secretion (2014)
  • Author(s): Satoshi Asano, Tomomi Nemoto, Tomoya Kitayama, Kae Harada, Jun Zhang, Kana Harada, Isei Tanida, Masato Hirata, and Takashi, Kanematsu
  • Journal Title: Biological Open Volume: 3 Issue: 6 Pages: 463-474
  • DOI: 10.1242/bio.20147591
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced desensitization followed by unusual resensitization in GABAA receptors in phospholipase C-related catalytically inactive protein-1/2 double-knockout mice (2014)
  • Author(s): Toyoda H, Saito M, Sato H, Tanaka T, Ogawa T, Yatani H, Kawano T, Kanematsu T, Hirata M, Kang Y
  • Journal Title: Pflugers Archiv - European Journal of Physiology Volume: (Epub ahead of print) Issue: 2 Pages: 267-284
  • DOI: 10.1007/s00424-014-1511-5
  • Peer Reviewed / Open Access
• [Journal Article] Palliation of bone cancer pain by antagonists of platelet-activating factor receptors. (2014)
  • Author(s): Morita K, Shiraishi S, Motoyama N, Kitayama T, Kanematsu T, Uezono Y, Dohi T.
  • Journal Title: PLoS ONE Volume: 9 Issue: 3 Pages: e91746-e91746
  • DOI: 10.1371/journal.pone.0091746
  • Peer Reviewed / Open Access
• [Presentation] Phospholipase C-related but catalytically inactive protein (PRIP) modulates beta-adrenergic receptor-mediated thermogenesis in brown adipocytes (2015)
  • Author(s): 大植香菜, 入舩正浩, 兼松 隆
  • Organizer: 第48回広島大学歯学会総会
  • Place of Presentation: 広島
  • Year and Date: 2015-06-27
• [Presentation] PRIPは褐色脂肪細胞における非ふるえ熱産生を調節している (2015)
  • Author(s): 兼松隆, 大植香菜
  • Organizer: 第127回日本薬理学会近畿部会
  • Place of Presentation: 岐阜
  • Year and Date: 2015-06-26
• [Presentation] PRIPは褐色脂肪細胞における非ふるえ熱産生を調節している (2015)
  • Author(s): 兼松隆、大植香菜
  • Organizer: 第127回日本薬理学会近畿部会
  • Place of Presentation: 岐阜市 長良川国際会議場
  • Year and Date: 2015-06-26
• [Presentation] PRIP regulates feeding behavior and energy metabolism (2015)
  • Author(s): Takashi Kanematsu, Kana Oue
  • Organizer: The International Symposium on Neuroscience in Orofacial sensory-motor functions
  • Place of Presentation: 大阪市 大阪大学中之島センター
  • Year and Date: 2015-05-11 – 2015-05-12
  • Invited
• [Presentation] PRIP regulates feeding behavior and energy metabolism. (2015)
  • Author(s): Takashi Kanematsu, Kana Oue
  • Organizer: The International Symposium on Neuroscience in Orofacial sensory-motor functions (ISNO2015)
  • Place of Presentation: Osaka
  • Year and Date: 2015-05-10
  • Int'l Joint Research / Invited
• [Presentation] PRIP欠損マウスにおける耐肥満性とエネルギー消費亢進の分子メカニズム (2015)
  • Author(s): 大植香菜、入舩正浩、兼松隆
  • Organizer: 2014年度「食と健康セミナー」
  • Place of Presentation: 広島市 広島女学院大学
  • Year and Date: 2015-02-14
• [Presentation] 脂肪細胞における脂肪代謝とエネルギー調節 (2014)
  • Author(s): 兼松隆
  • Organizer: 第２回口腔科学研究会
  • Place of Presentation: 盛岡市 岩手医科大学
  • Year and Date: 2014-12-12 – 2014-12-13
  • Invited
• [Presentation] PRIP-regulated GABA signaling involved in regulation of feeding behavior (2014)
  • Author(s): 兼松隆
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡市 福岡国際会議場
  • Year and Date: 2014-09-25 – 2014-09-27
  • Invited
• [Presentation] PRIPが調節するGABAシグナリングと摂食調節 (2014)
  • Author(s): 兼松隆
  • Organizer: 第１回口腔科学研究会
  • Place of Presentation: 大阪市 大阪大学
  • Year and Date: 2014-09-07
• [Presentation] Mice lacking phospholipase C-related but catalytically inactive protein (PRIP) are protected from high-fat diet-induced obesity (2014)
  • Author(s): 大植香菜, 入舩正浩, 兼松 隆
  • Organizer: 第47回広島大学歯学会総会
  • Place of Presentation: 広島市 広島大学
  • Year and Date: 2014-06-21
• [Remarks] 細胞分子薬理学HP
  • URL: http://home.hiroshima-u.ac.jp/shiyaku/
• [Remarks] 「研究最前線」より 生体のエネルギー代謝や脂肪分解を制御する新たな分子
  • URL: http://s-ja.hiroshima-u.jp/upload_files/download_files/BHS_NEWS_8_Kanematsu_0.pdf
• [Remarks] 歯学部案内
  • URL: http://hiroshima-u.jp/dent/brochure/information
• [Remarks] 広島大学細胞分子薬理学教室
  • URL: http://home.hiroshima-u.ac.jp/shiyaku/