Investigation of the physiological function of Slc22a18, a candidate identified by a genetic analysis on animal models for visceral fat accumulation

• Project/Area Number: 26461357
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kyorin University
• Principal Investigator: GOTODA TAKANARI 杏林大学, 医学部, 教授 (60322062)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: メタボリックシンドローム / 脂肪蓄積 / トランスポーター / ビリルビン / 内臓脂肪蓄積 / 遺伝子 / SLC / SHR

Outline of Final Research Achievements

Genetic factors underlying visceral fat accumulation, a principal component of the metabolic syndrome (MS), remain largely unknown. In this study, visceral fat accumulation was accelerated in transgenic mice overexpressing SLC22A18, a candidate gene revealed by our previous genetic studies on animal models. Oppositely, fat volume was decreased in SLC22A18 knockout mice as compared with normal mice. These results indicated that SLC22A18 plays a crucial role in regulating visceral fat accumulation. A series of our experiments have revealed a promising candidate for endogenous substrates transported by SLC22A18. Thus, SLC22A18 could be a novel therapeutic target for metabolic syndrome via its regulatory function upon visceral fat accumulation.

Research Products

• [Journal Article] KLF15 Enables Rapid Switching between Lipogenesis and Gluconeogenesis during Fasting. (2016)
  • Author(s): Takeuchi Y, Yahagi N, Aita Y, Murayama Y, Sawada Y, Piao X, Toya N, Oya Y, Shikama A, Takarada A, Masuda Y, Nishi M, Kubota M, Izumida Y, Yamamoto T, Sekiya M, Matsuzaka T, Nakagawa Y, Urayama O, Kawakami Y, Iizuka Y, Gotoda T, Itaka K, Kataoka K, Nagai R, Kadowaki T, Yamada N, Lu Y, Jain MK, and Shimano H
  • Journal Title: Cell Rep. Volume: 16 Issue: 9 Pages: 2373-2386
  • DOI: 10.1016/j.celrep.2016.07.069
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] From Association to Function in the Post-GWAS Era (2015)
  • Author(s): Ｔａｋａｎａｒｉ Ｇｏｔｏｄａ
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 22 Issue: 5 Pages: 442-444
  • DOI: 10.5551/jat.ED017
  • NAID: 130005071040
  • ISSN: 1340-3478, 1880-3873
  • Open Access
• [Presentation] メタボリックシンドローム関連遺伝子KAT-1（kynurenine aminotransferase-1）の糖代謝に及ぼす影響 (2016)
  • Author(s): 山本隆史、飯塚陽子、藤田敏郎、後藤田貴也
  • Organizer: 第48回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-07-14
• [Presentation] SHRの遺伝解析により同定された内臓脂肪蓄積関連遺伝子Slc22a18の生理的機能の解析 (2015)
  • Author(s): 山本隆史、 後藤田貴也
  • Organizer: 第88回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] SHRの遺伝解析により同定された内臓脂肪蓄積関連遺伝子Slc22a18の生理的機能の解析 (2015)
  • Author(s): 山本隆史、 飯塚陽子、 藤田敏郎、 後藤田貴也
  • Organizer: 第47回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2015-07-09
• [Presentation] 高血圧自然発症ラット(SHR)の遺伝解析から同定された内臓脂肪蓄積関連遺伝子Slc22a18の発現調節機構および肝脂肪蓄積への関与の解明 (2014)
  • Author(s): 後藤田 貴也、 山本 隆史
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-17