Individual differences in time course of sleeping energy metabolism in relation to metabolic diseases

• Project/Area Number: 20H04120
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: University of Tsukuba
• Principal Investigator: Tokuyama Kumpei 筑波大学, 国際統合睡眠医科学研究機構, 教授 (00207565)
• Co-Investigator(Kenkyū-buntansha): 鈴木 陽子 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (00813453) ; 麻見 直美 筑波大学, 体育系, 教授 (10300005) ; 矢島 克彦 城西大学, 薬学部, 助教 (70632264) ; 下山 寛之 筑波大学, 体育系, 助教 (80760652) ; 田名辺 陽子 筑波大学, 体育系, 研究員 (90781873)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2020: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: メタボリックチャンバー / ヒューマンカロリメータ / エネルギー代謝 / 睡眠時エネルギー代謝 / 尿メタボローム / ヒューマン・カロリメータ / 呼吸商 / 国際共同データベース / 代謝的柔軟性 / 脂肪酸化 / 炭水化物酸化 / 呼吸交換比 / RQ / インスリン抵抗性

Outline of Research at the Start

睡眠はその間の絶食時間をいかに乗り切るかという代謝調節の課題に対処しつつ進行している。申請者らは24時間のエネルギー代謝測定から、絶食が続くにもかかわらず睡眠の後半には呼吸商（RQ）が上昇に転じて炭水化物の酸化が亢進することを見出した。またRQの経時変化の個人差は特に睡眠中に顕在化し、また男女差があることを見出している。本研究ではこの睡眠時のエネルギー代謝の個人差の要因について、多様な被験者の代謝測定結果の比較と尿メタボローム解析による探索的研究から解析を進める。更にこれらの測定結果を国際共同データ・ベースとして構築し、エネルギー代謝の比較研究（国際比較、年代比較など）の基盤を築く。

Outline of Final Research Achievements

Sleep is consolidated into a single prolonged period in humans, and its metabolic consequence is to impose an extended duration of fasting. The present study revealed that 1) RQ begins to increase prior to awakening, and sleeping energy metabolism is not a simple result of prolonged fasting. The increase in RQ of female subjects begins earlier than that of male subjects. Transient decrease RQ during sleep in aged subjects is smaller than that of young subjects. Individual variation in RQ become evident during sleep. Oxidized substrate during sleep is flexibly switched during sleep, and blunted nocturnal decrease in RQ may be an earliest event leading to metabolic inflexibility and insulin resistance..
Urinary metabolome analysis identified several marker such as acylcarnitin, succinate, leucine and isoleucine, which can be a marker of metabolic flexibility.
To get bigger picture of energy metabolism, we began to set-up an international data-base for metabolic chamber study.

Academic Significance and Societal Importance of the Research Achievements

本研究ではこの睡眠時のエネルギー代謝、特に呼吸商（RQ）の経時変化の個人差の要因について検討した。睡眠時のRQの経時変化の個人差がインスリン抵抗性発症に向けた最も初期の現象であることが示唆された。今後、インスリン抵抗性や糖尿病の病因解明につながる知見だと考えている。
本研究は申請者らの過去のエネルギー代謝測定データの再解析に加えて、高齢者や無月経女性アスリートの測定を加えて行った。国内外の研究機関に蓄積されているデータと統合したデータベースを設立することでヒトのエネルギー代謝調節の全体像が明らかになると考えている。国際共同データベースが将来のこの分野の発展に大きく寄与すると考えている。

Research Products

• [Journal Article] Prevalence and risk factors of poor subjective sleep quality in elite judo athletes (2023)
  • Author(s): Monma Takafumi、Matsui Takashi、Inoue Kosei、Masuchi Katsuyuki、Okada Takashi、Tamura Masahiro、Ishii Takanori、Satoh Makoto、Tokuyama Kumpei、Takeda Fumi
  • Journal Title: Sleep and Biological Rhythms Volume: 1 Issue: 3 Pages: 1-9
  • DOI: 10.1007/s41105-023-00444-6
  • Peer Reviewed / Open Access
• [Journal Article] Exercise Timing Matters for Glycogen Metabolism and Accumulated Fat Oxidation over 24 h (2023)
  • Author(s): Iwayama Kaito、Seol Jaehoon、Tokuyama Kumpei
  • Journal Title: Nutrients Volume: 15 Issue: 5 Pages: 1109-1109
  • DOI: 10.3390/nu15051109
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Food Quotient Assessments Using One-Week Dietary Records and Food Frequency Questionnaires of Young Japanese Runners (2022)
  • Author(s): Uchizawa Akiko、Funayama Airi、Osumi Haruka、Enomoto Yasushi、Zhang Simeng、Tokuyama Kumpei、Omi Naomi、Sagayama Hiroyuki
  • Journal Title: Journal of Nutritional Science and Vitaminology Volume: 68 Issue: 1 Pages: 47-54
  • DOI: 10.3177/jnsv.68.47
  • NAID: 130008164779
  • ISSN: 0301-4800, 1881-7742
  • Year and Date: 2022-02-28
  • Peer Reviewed / Open Access
• [Journal Article] Effects of nocturnal light exposure on circadian rhythm and energy metabolism in healthy adults: A randomized crossover trial (2022)
  • Author(s): Choi Youngju、Nakamura Yuki、Akazawa Nobuhiko、Park Insung、Kwak Hyo-Bum、Tokuyama Kumpei、Maeda Seiji
  • Journal Title: Chronobiology International Volume: 39 Issue: 4 Pages: 602-612
  • DOI: 10.1080/07420528.2021.2014517
  • Peer Reviewed / Open Access
• [Journal Article] Bidirectional associations between physical activity and sleep in order adults: a multilevel analysis using polysomnography (2022)
  • Author(s): Jaehoon Seol, Jaehee Lee, Insung Park, Kumpei Tokuyama, Shoji Fukusumi, Toshio Kokubo, Masashi Yanagisawa, Tomohiro Okura
  • Journal Title: Scientific Report Volume: 12 Issue: 1 Pages: 15399-15399
  • DOI: 10.1038/s41598-022-19841-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Instability of non-REM sleep in older women evaluated by sleep-stage transition and envelope analyses (2022)
  • Author(s): Park Insung、Kokudo Chihiro、Seol Jaehoon、Ishihara Asuka、Zhang Simeng、Uchizawa Akiko、Osumi Haruka、Miyamoto Ryusuke、Horie Kazumasa、Suzuki Chihiro、Suzuki Yoko、Okura Tomohiro、Diaz Javier、Vogt Kaspar E.、Tokuyama Kumpei
  • Journal Title: Frontiers in Aging Neuroscience Volume: 14 Pages: 1-12
  • DOI: 10.3389/fnagi.2022.1050648
  • Peer Reviewed / Open Access
• [Journal Article] Metabolic flexibility during sleep. (2021)
  • Author(s): Zhang S, Tanaka Y, Ishihara A, Uchizawa A, Park I, Iwayama K, Ogata H, Yajima K, Omi N, Satoh M, Yanagisawa M, Sagayama H, Tokuyama K.
  • Journal Title: Scientific Reports Volume: 11 Pages: 17849-17849
  • Peer Reviewed / Open Access
• [Journal Article] Metabolic responses to polychromatic LED and OLED light at night (2021)
  • Author(s): Asuka Ishihara, Insung Park, Yoko Suzuki, Katsuhiko Yajima, Huiyun Cui, Masashi Yanagisawa, Takeshi Sano, Junji Kido, Kumpei Tokuyama
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 12402-12402
  • DOI: 10.1038/s41598-021-91828-6
  • Peer Reviewed / Open Access
• [Journal Article] Novel Equations to Estimate Resting Energy Expenditure during Sitting and Sleeping (2021)
  • Author(s): Uchizawa Akiko、Hibi Masanobu、Sagayama Hiroyuki、Zhang Simeng、Osumi Haruka、Tanaka Yoshiaki、Park Insung、Tokuyama Kumpei、Omi Naomi
  • Journal Title: Annals of Nutrition and Metabolism Volume: 77 Issue: 3 Pages: 159-167
  • DOI: 10.1159/000516174
  • Peer Reviewed
• [Journal Article] Changes in sleeping energy metabolism and thermoregulation during menstrual cycle. (2020)
  • Author(s): Zhang, S. Osumi, H. Uchizawa, A. Hamada, H. Park, I. Suzuki, Y. Tanaka, Y. Ishihara, A. Yajima, K. Seol, J. Satoh, M. Omi, N. Tokuyama, K.
  • Journal Title: Physiological Reports Volume: 8 Issue: 2
  • DOI: 10.14814/phy2.14353
  • Peer Reviewed / Open Access
• [Journal Article] Effect of a single bout of exercise on clock gene expression in human leukocyte (2020)
  • Author(s): Tanaka Yoshiaki、Ogata Hitomi、Kayaba Momoko、Ando Akira、Park Insung、Yajima Katsuhiko、Araki Akihiro、Suzuki Chihiro、Osumi Haruka、Zhang Simeng、Ishihara Asuka、Takahashi Keigo、Shoda Junichi、Nabekura Yoshiharu、Satoh Makoto、Tokuyama Kumpei
  • Journal Title: Journal of Applied Physiology Volume: 128 Issue: 4 Pages: 847-854
  • DOI: 10.1152/japplphysiol.00891.2019
  • Peer Reviewed / Open Access
• [Journal Article] Skipping breakfast for 6 days delayed the circadian rhythm of the body temperature without altering clock gene expression in human leukocytes (2020)
  • Author(s): Hitomi Ogata, Masaki Horie, Momoko Kayaba, Yoshiaki Tanaka, Akira Ando, Insung Park, Simeng Zhang, Katsuhiko Yajima, Jun-ichi Shoda, Naomi Omi, Miki Kaneko, Ken Kiyono, Makoto Satoh, Kumpei Tokuyama
  • Journal Title: Nutrients Volume: 12 Issue: 9 Pages: 2797-2797
  • DOI: 10.3390/nu12092797
  • Peer Reviewed / Open Access
• [Journal Article] Effects of exercise before breakfast on plasma free fatty acid profile and 24-h fat oxidation (2020)
  • Author(s): Kaito Iwayama, Ayane Ogawa, Yoshiaki Tanaka, Katsuhiko Yajima, Insung Park, Akira Ando, Hitomi Ogata, Momoko Kayaba, Simeng Zhang, Fumiya Tanji, Yoshiharu Nabekura, Kouhei Yamamoto, Kumpei Tokuyama
  • Journal Title: Metabol Open Volume: 8 Pages: 100067-100067
  • DOI: 10.1016/j.metop.2020.100067
  • Peer Reviewed / Open Access
• [Journal Article] Subacute ingestion of caffeine and oolong tea increases fat oxidation without affecting energy expenditure and sleep architecture: a randomized, placebo-controlled, double-blinded cross-over trial. (2020)
  • Author(s): Zhang, S., Takano, J., Murayama, N., Tominaga, M., Abe, T., Park, I., Seol, J., Ishihara, A., Tanaka, Y., Yajima, K., Suzuki, Y., Suzuki, C., Fukusumi, S., Yanagisawa, M., Kokubo, T., Tokuyama, K.
  • Journal Title: Nutrients. Volume: 12 Issue: 12 Pages: 3671-1680
  • DOI: 10.3390/nu12123671
  • Peer Reviewed
• [Presentation] Lack of light in the evening modulates thermal and metabolic physiology. (2022)
  • Author(s): Ishihara A, Yoshitake R, Sekiguchi R, Kioka K, Park I, Yajima K, Omi N, Tokuyama K.
  • Organizer: Recent Advances & Controversies in the Measurement of Energy Metabolism.
  • Int'l Joint Research
• [Presentation] Metabolic flexibility during sleep. (2022)
  • Author(s): Park I, Yoshitake R, Kioka K, Ishihara A, Yajima K, Omi N, Kanbayashi T, Yanagisawa M, Tokuyama K
  • Organizer: Recent Advances & Controversies in the Measurement of Energy Metabolism.
  • Int'l Joint Research