The role of fructose metabolism in the development of chronic kidney disease and hypertension.

• Project/Area Number: 15K09255
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Nagoya University
• Principal Investigator: ISHIMOTO TAKUJI 名古屋大学, 医学部附属病院, 助教 (00534835)
• Co-Investigator(Kenkyū-buntansha): 丸山 彰一 名古屋大学, 医学系研究科, 教授 (10362253) ; 小杉 智規 名古屋大学, 医学部附属病院, 講師 (90584681)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 塩分感受性高血圧 / フルクトース / ケトヘキソキナーゼ / 高血圧 / 塩分感受性 / フルクトキナーゼ / 慢性腎臓病

Outline of Final Research Achievements

The aim of this study is to elucidate the role of fructose metabolism by the primary enzyme of fructose, ketohexokinase (KHK) in hypertension. In this study, by using KHK knockout mice (KHK-KO), we found that the combination of fructose and high salt induced the elevation of blood pressure with decrease of sodium excretion and increase of mRNA expression of NHE3 in kidney in wild type mice (WT), but not in KHK-KO mice, and that fructose stimulation increased NHE activity accompanied by a decrease in intracellular cAMP that is dependent on KHK. These results suggest that fructose metabolism by KHK is involved in the development of salt-sensitive hypertension through increases of renal sodium reabsorption by NHE3.

Research Products

• [Int'l Joint Research] University of Colorado, Denver(米国)
• [Int'l Joint Research] University of Colorado Denver/Renal Diseases and Hypertension(米国)
• [Int'l Joint Research] University of Colorado Denver(米国)
• [Presentation] Combination of high fructose and high salt increases renal sodium reabsorption and blood pressure that is dependent on ketohexokinase (2017)
  • Author(s): Takahiro Hayasaki, Takuji Ishimoto, Tomohito Doke, Tomoki Kosugi, Miguel A. Lanaspa, Naotake Tsuboi, Richard J. Johnson, Shoichi Maruyama.
  • Organizer: American Society of Nephrology
  • Int'l Joint Research
• [Presentation] 血圧調節とナトリウム出納におけるフルクトース代謝の関与についての検討 (2016)
  • Author(s): 早崎貴洋,石本卓嗣,道家智仁,船橋嘉夫,森佳子,西尾文利,吉岡知輝,増田智広,佐藤由香,加藤規利,小杉智規,門松健治,松尾清一,丸山彰一
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-06-17
• [Presentation] 血圧調節とナトリウム出納におけるフルクトース代謝の関与についての検討 (2016)
  • Author(s): 早崎貴洋、石本卓嗣、丸山彰一
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県、横浜）
  • Year and Date: 2016-06-17
• [Presentation] Combination of High Fructose and High Salt affects sodium absorption and induce the elevation of blood pressure that is Dependent on Ketohexokinase (2016)
  • Author(s): 早崎貴洋、石本卓嗣、丸山彰一
  • Organizer: 53RD ERA-EDTA CONGRESS, VIENNA 2016
  • Place of Presentation: Austria Center Vienna（Vienna, Austria）
  • Year and Date: 2016-05-21
  • Int'l Joint Research