Clarification the regulation of short chain fatty acids transport function in the liver.

Research Project

Project/Area Number	16K08555
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	General pharmacology
Research Institution	Kyorin University
Principal Investigator	Fukutomi Toshiyuki 杏林大学, 医学部, 助教 (30439187)
Co-Investigator(Kenkyū-buntansha)	木村徹杏林大学, 医学部, 学内講師 (30433725)
Project Period (FY)	2016-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	短鎖脂肪酸 / 輸送体 / トランスポーター / プロテオミクス / 酪酸 / OAT7 / 相互作用 / 有機アニオン / 質量分析 / PDZK1 / プロピオン酸 / PDZ / 薬理学
Outline of Final Research Achievements	Short chain fatty acids, including acetate, propionate and butyrate, have been shown to regulate various metabolic processes such as energy and lipid metabolism. Of these short chain fatty acids, butyrate has been identified as a ligand for GRP41/43. Butyrate blood levels would correlate with GLP-1 production and one of the determinants of the butyrate level is its uptake/release by the liver. Human organic anion transporter 7 (OAT7) / organic anion transporter 2 (OAT2) expressed at hepatocyte membrane, has been functionally characterized as an exchange transporter of butyrate / propionate with sulfate conjugated steroids. The purpose of this study is to clarify the regulation of butyrate / propionate transports function. As a first step we attempted to identify OAT7 / OAT2 interacting proteins by yeast two-hybrid and immunoprecipitation followed by mass spectrometry in human liver cell lines. One of the proteins identified by yeast two-hybrid was likely to regulate OAT7 function.
Academic Significance and Societal Importance of the Research Achievements	本研究は、これまで栄養素としての位置づけが大きかった短鎖脂肪酸を単なる栄養素としてではなく、エネルギー恒常性維持を中心とした生理現象に重要なシグナル分子として捉え、血中の短鎖脂肪酸の濃度調節機構を解明するものである。特に、血中の短鎖脂肪酸の濃度を決定づけるのに重要な肝臓での短鎖脂肪酸取込み調節機構を明らかにすることに着目した。本研究成果の一つである酪酸輸送体OAT7相互作用タンパク質と酪酸輸送機能調節の可能性は、肝臓での酪酸取込みの新たな知見であり、エネルギー恒常性維持の理解が進むと考えられる。