Caroline restriction prevents lacrimal hypofunction in rat visual display terminal user model: a pivotal role of endogenous D-3-hydroxybutyrate

• Project/Area Number: 15K00843
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: Keio University
• Principal Investigator: Nakamura Shigeru 慶應義塾大学, 医学部(信濃町), 共同研究員 (00599269)
• Research Collaborator: IZUTA Yusuke
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 栄養制限 / ドライアイ / 酸化ストレス / ケトン体

Outline of Final Research Achievements

Despite calorie restriction (CR) being the oldest and most robust dietary intervention that provides various health benefits, the mechanism underlying this process is still under intensive investigation. D-3-hydroxybutyrate (3HB), a major circulating ketone body, has been proposed to associated with the benefits of CR. In the present study, we explored the possible role of 3HB on the tear secretion by rat dry eye model. Rats were assigned to three groups: AL, ad libitum-fed animals, and CR, intermittent fasting rats, AL+3-HB, 3HB diluted with saline was injected into rat dorsal skin at a dose of 2000 mg/kg/day. Change in tear secretion was significantly suppressed in the CR and AL+3HB compare to the AL. Significant suppression of ROS generation was observed in the CR and AL+3HB compared to that in the AL group. Our findings suggest that increased 3-HB play an important role of tear secretion which can be improved by CR in VDT associated dry eye.

Research Products

• [Journal Article] Ketone body 3-hydroxybutyrate mimics calorie restriction via the Nrf2 activator, fumarate, in the retina. (2018)
  • Author(s): Izuta Y, Imada T, Hisamura R, Oonishi E, Nakamura S, Inagaki E, Ito M, Soga T, Tsubota K.
  • Journal Title: Aging Cell. Volume: 17 Issue: 1 Pages: 1-15
  • DOI: 10.1111/acel.12699
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Ketone body 3-hydroxybutyrate mimics calorie restriction and shows retinal protective effect through altering the metabolic profile. (2017)
  • Author(s): Yusuke Izuta, Toshihiro Imada, Ryuji Hisamura, Shigeru Nakamura, Kazuo Tsubota
  • Organizer: Keystone Symposia ：Aging and Mechanisms of Aging-Related Disease
  • Int'l Joint Research