Gut Microbiota-Derived Short Chain Fatty Acids Accelerate Food-Induced Circadian Clock Entrainment in Mouse Peripheral Tissue

• Project/Area Number: 15K18981
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Waseda University
• Principal Investigator: Tahara Yu 早稲田大学, 高等研究所, 助教 (80707399)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 体内時計 / 腸内細菌 / 末梢臓器 / 概日時計 / 肝臓 / 短鎖脂肪酸

Outline of Final Research Achievements

In this study, we demonstrated the effect of microbiota-derived short-chain fatty acid (SCFA) on the circadian clock system in mouse peripheral clocks. Cecal pH was lower and amount of cecal SCFA was higher in the beginning of dark period. Oral injection of SCFA in the daytime caused phase-advance of peripheral clocks. SCFA also caused phase entrainment of cellular clocks in fibroblasts with dose- and time-of-day dependency. In addition, fiber rich diet enhanced food-induced peripheral clock entrainment. Thus, our study revealed first application of chrono-nutrition using microbiota-derived SCFA.

Research Products

• [Int'l Joint Research] UCLA(米国)
• [Journal Article] Positive association between physical activity and PER3 expression in older adults (2017)
  • Author(s): Takahashi M, Haraguchi A, Tahara Y, Aoki N, Fukazawa M, Tanisawa K, Ito T, Nakaoka T, Higuchi M, Shibata S.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 39771-39771
  • DOI: 10.1038/srep39771
  • Peer Reviewed / Open Access
• [Journal Article] Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation (2017)
  • Author(s): Tahara Y, Takatsu Y, Shiraishi T, Kikuchi Y, Yamazaki M, Motohashi H, Muto A, Sasaki H, Haraguchi A, Kuriki D, Nakamura TJ, Shibata S
  • Journal Title: npj Aging and Mechanisms and Disease Volume: 3 Issue: 1 Pages: 16030-16030
  • DOI: 10.1038/npjamd.2016.30
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Potent Effects of Flavonoid Nobiletin on Ampliturde, Period, and Phase of the Circadian Clock Rhythm in PER2::LUC Mouse Embryonic Fibroblasts. (2017)
  • Author(s): Shinozaki A, Misawa K, Ikeda Y, Haraguchi A, Kamagata M, Tahara Y, Shibata S
  • Journal Title: PLoS One Volume: 12 Issue: 2 Pages: e0170904-e0170904
  • DOI: 10.1371/journal.pone.0170904
  • Peer Reviewed / Open Access
• [Journal Article] Forced rather than voluntary exercise entrains peripheral clocks via a corticosterone/noradrenaline increase in PER2::LUC mice. (2016)
  • Author(s): Sasaki H, Hattori Y, Ikeda Y, Kamagata M, Iwami S, Yasuda S, Tahara Y, Shibata S
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 27607-27607
  • DOI: 10.1038/srep27607
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Abnormal tuning of the hepatic circadian metabolic rhythms in lung cancer. (2016)
  • Author(s): Tahara Y and Shibata S
  • Journal Title: Hepatology Volume: 65 Issue: 3 Pages: 1061-1064
  • DOI: 10.1002/hep.28982
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The mammalian circadian clock and its entrainment by stress and exercise. (2016)
  • Author(s): Tahara Y, Aoyama S, Shibata S
  • Journal Title: J Physiological Sciences Volume: 印刷中
  • NAID: 40021064512
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Circadian rhythms of liver physiology and disease: experimental and clinical evidence (2016)
  • Author(s): Tahara Y, Shibata S
  • Journal Title: Nature Reviews Gastroenterology and Hepatology Volume: 13 Issue: 4 Pages: 217-226
  • DOI: 10.1038/nrgastro.2016.8
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] In vitro and in vivo Phase Changes of the Mouse Circadian Clock by Oxidative Stress (2016)
  • Author(s): Tahara Y, Yokota A, Shiraishi T, Yamada S, Haraguchi A, Shinozaki A, Shibata S
  • Journal Title: Journal of Circadian Rhythms Volume: 14 Issue: 1 Pages: 1-7
  • DOI: 10.5334/jcr.136
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Entrainment of the mouse circadian clock by sub-acute physical and psychological stress. (2015)
  • Author(s): Tahara Y, Shiraishi T, Kikuchi Y, Haraguchi A, Kuriki D, Sasaki H, Motohashi H, Sakai T, Shibata S.
  • Journal Title: Sci Rep Volume: 15 Issue: 1 Pages: 11417-11417
  • DOI: 10.1038/srep11417
  • Peer Reviewed / Open Access
• [Presentation] Entrainment ability of the peripheral circadian clocks by light, food, stress, and exercise in aged mice (2016)
  • Author(s): 田原 優
  • Organizer: SRBR Meeting 2016
  • Place of Presentation: フロリダ
  • Year and Date: 2016-05-21
  • Int'l Joint Research
• [Presentation] 今年のトレンドとなるか 「時間栄養学」の最新研究 (2016)
  • Author(s): 田原 優
  • Organizer: 2016 健食原料・OEM展
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2016-04-18
  • Invited
• [Presentation] 体内時計の食事・運動による時刻合わせー老化による影響ー (2016)
  • Author(s): 田原 優
  • Organizer: 時間栄養科学研究会
  • Place of Presentation: 東京農業大学
• [Presentation] 体内時計から考える健康科学とは (2016)
  • Author(s): 田原 優
  • Organizer: SCJSF Meeting
  • Place of Presentation: UCLA
  • Invited
• [Presentation] マウスの体内時計の老化と食・運動との関係 (2016)
  • Author(s): 田原 優
  • Organizer: SAM研究協議会
  • Place of Presentation: 京都大学
  • Invited
• [Book] マウス表現型解析スタンダード (2016)
  • Author(s): 柴田 重信、田原 優
  • Total Pages: 6
  • Publisher: 羊土社