Histological analysis of novel transforming mechanisms in adipocytes

• Project/Area Number: 17K08508
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Yamagata University
• Principal Investigator: Nakano Tomoyuki 山形大学, 医学部, 准教授 (00333948)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 脂肪組織 / ベージュ化 / ジアシルグリセロールキナーゼ / 高脂肪食 / 寒冷暴露 / 脂肪細胞 / 体温産生 / インスリン / 褐色化 / 体温 / 形質転換

Outline of Final Research Achievements

Diacylglycerol kinase (DGK) is an enzyme that converts DG to phosphatidic acid. DG is known as an intermediate product for triglyceride synthesis, but also is known as a lipidic second messenger. Thus, DG serves as a hub between energy metabolism and intracellular signaling. DGKe resides in the endoplasmic reticulum (ER). Since ER is known as a central site for lipid synthesis, current study focused on DGKe using its knock out mice. Two animal experiments were conducted in this project. One experiment revealed that beige adipogenesis was induced in the epididymal white adipose tissue（WAT） of DGKe-KO mice under long term High fat diet（HFD）） feeding. The other experiment showed that DGKe-KO mice was susceptible to cold exposure. To compensate body heat loss, beige adipogenesis was induced in inguinal WAT. Present projected concluded that stress conditions in adipose tissue such as HFD feeding and cold exposure, DGKe-deletion confers susceptibility to adipose tissue remodeling.

Academic Significance and Societal Importance of the Research Achievements

白色脂肪組織中に褐色脂肪細胞が誘導される褐色化は、肥満治療の観点で注目を集めているが、脂肪細胞の形質転換メカニズムという基礎的な、解剖学的に興味深い現象である。本研究プロジェクトの結果から、高エネルギー条件や寒冷環境において、DGKe欠損によるDG代謝の低下が褐色化を促進するという新規メカニズムが明らかとなった。特に、高エネルギー条件においては、DGKeと同じく小胞体に局在するシクロオキシゲナーゼ2依存的に褐色化が生じることは、小胞体における脂質代謝が褐色化に影響を与える点で興味深い知見である。

Research Products

• [Int'l Joint Research] ユタ大学(米国)
• [Journal Article] Diacylglycerol Kinase ε in Adipose Tissues: A Crosstalk Between Signal Transduction and Energy Metabolism (2022)
  • Author(s): Nakano Tomoyuki、Goto Kaoru
  • Journal Title: Frontiers in Physiology Volume: 13 Pages: 815085-815085
  • DOI: 10.3389/fphys.2022.815085
  • Peer Reviewed / Open Access
• [Journal Article] Cellular expression and subcellular localization of diacylglycerol kinase γ in rat brain (2021)
  • Author(s): Hozumi Y, Nakano T, Goto K.
  • Journal Title: Biomedical Research Volume: 42 Issue: 1 Pages: 33-42
  • DOI: 10.2220/biomedres.42.33
  • NAID: 130007983453
  • ISSN: 0388-6107, 1880-313X
  • Year and Date: 2021-02-10
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of p53 and NF-κB transactivation activities by DGKζ in catalytic activity-dependent and -independent manners (2021)
  • Author(s): Tanaka Toshiaki、Nakano Tomoyuki、Hozumi Yasukazu、Martelli Alberto M.、Goto Kaoru
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Volume: 1868 Issue: 4 Pages: 118953-118953
  • DOI: 10.1016/j.bbamcr.2021.118953
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mice lacking DGKepsilon show increased beige adipogenesis in visceral WAT after long-term high fat diet in a COX-2-dependent manner. (2020)
  • Author(s): Nakano T., Topham M.K. and Goto K.
  • Journal Title: Advances in Biological Regulation Volume: In press Pages: 100659-100659
  • DOI: 10.1016/j.jbior.2019.100659
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Deletion of diacylglycerol kinase ε confers susceptibility to obesity via reduced lipolytic activity in murine adipocytes (2018)
  • Author(s): Nakano T, Seino K, Wakabayashi I, Stafforini DM, Topham MK, Goto K
  • Journal Title: FASEB J. Volume: - Issue: 8 Pages: 4121-4130
  • DOI: 10.1096/fj.201701050r
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] DgMab-6: Anti-Human DGK gamma Monoclonal Antibody for immunocytochemistry (2018)
  • Author(s): Nakano T., Ogasawara S., Tanaka T., Hozumi Y., Yamaki A., Sakane F, Shirai Y., Nakamura T., Yanaka M., Yamada S., Kaneko M.K., Kato Y., Goto K
  • Journal Title: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Volume: 37 Issue: 5 Pages: 229-232
  • DOI: 10.1089/mab.2014.0018
  • Peer Reviewed
• [Journal Article] Deletion of diacylglycerol kinase e confers susceptibility to obesity via reduced lipolytic activity in murine adipocytes. (2018)
  • Author(s): Nakano T., Seino K., Wakabayashi I., Stafforini D.M., Topham M.K. and Goto K.
  • Journal Title: FASEB J Volume: in press
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] DGKζ ablation engenders upregulation of p53 level in the spleen upon whole-body ionizing radiation (2017)
  • Author(s): Tanaka T., Iseki K., Tanaka K., Nakano T., Iino M. and Goto K.
  • Journal Title: Advances in Biological Regulation Volume: 17 Pages: 30158-30166
  • Peer Reviewed
• [Presentation] DGKε欠損マウスにおける適応熱産生機構の解析 (2022)
  • Author(s): 中野知之、後藤 薫
  • Organizer: 127回日本解剖学会総会
• [Presentation] DGKε遺伝子欠損マウスはインスリン依存的に非震え熱産生機機構の障害を引き起こす (2021)
  • Author(s): 中野知之、後藤 薫
  • Organizer: 第67回日本解剖学会東北・北海道連合支部学術集会
• [Presentation] DGK epsilon-deficient mice show impaired adaptive thermogenesis under cold exposure (2021)
  • Author(s): Nakano T. and Goto K
  • Organizer: 第126回日本解剖学会総会
• [Presentation] DGK epsilon deficiency renders mice resistant to LPS-induced inflammatory reaction (2021)
  • Author(s): Ozawa A., Nakano T., Iseki K. and Goto K
  • Organizer: 第126回日本解剖学会総会
• [Presentation] DGKε欠損マウスにおける体温調節メカニズムの異常 (2020)
  • Author(s): 中野知之、後藤薫
  • Organizer: 第66回日本解剖学会東北・北海道連合支部学術集会
• [Presentation] DGKepsilon-deficient visceral adipose tissue is prone to phenotypic switching under high fat diet conditions. (2020)
  • Author(s): Nakano T. and Goto K.
  • Organizer: Obesity and NAFLD (B3) in Keystone symposia
  • Int'l Joint Research
• [Presentation] ε型ジアシルグリセロールキナーゼ欠損は皮下脂肪における褐色化を促進する (2020)
  • Author(s): 中野知之、後藤薫
  • Organizer: 第125回日本解剖学会総会
• [Presentation] ε型ジアシルグリセロールキナーゼ欠損は白色脂肪組織の褐色化を惹起する (2019)
  • Author(s): 中野知之、後藤薫
  • Organizer: 第65回日本解剖学会東北・北海道連合支部学術集会
• [Presentation] Diacylglycerol kinase epsilon欠損による脂肪組織リモデリングの解析-寒冷暴露による変化- (2019)
  • Author(s): 中野知之、後藤 薫
  • Organizer: 第124回日本解剖学会総会
• [Presentation] DGK epsilonはCOX-2を介して脂肪組織のリモデリングを制御する (2018)
  • Author(s): 中野知之、後藤 薫
  • Organizer: 第64回日本解剖学会東北・北海道連合支部学術集会
• [Presentation] Diacylglycerol kinase alpha negatively regulates the activation of myofibroblasts in mouse liver (2018)
  • Author(s): Nakano T., Seino K., Iseki K. and Goto K.
  • Organizer: American Society for Cell Biology
  • Int'l Joint Research
• [Presentation] DGKe deficiency impairs lipolytic activity and causes insulin insensitivity in adipocytes under (2018)
  • Author(s): Nakano T. and Goto K.
  • Organizer: Organ Crosstalk in Obesity and NAFLD (J3) in Keystone symposia
  • Int'l Joint Research
• [Presentation] ジアシルグリセロール代謝不全に起因する脂肪蓄積とインスリンシグナル異常 (2018)
  • Author(s): 中野知之、後藤 薫
  • Organizer: 第123回日本解剖学会総会シンポジウム
  • Invited
• [Presentation] DGKε欠損は白色脂肪細胞における脂質代謝異常を惹起する (2017)
  • Author(s): 中野知之、後藤 薫
  • Organizer: 第63回日本解剖学会東北・北海道連合支部学術集会
• [Book] In: Choi S. (eds) Encyclopedia of Signaling Molecules (2018)
  • Author(s): Diacylglycerol Kinase
  • Total Pages: 6
  • Publisher: Springer