L-serine enhances light-induced circadian phase resetting in mice and humans

Shinobu Yasuo, Ayaka Iwamoto, Sang Il Lee, Shotaro Ochiai, Rina Hitachi, Satomi Shibata, Nobuo Uotsu, Chie Tarumizu, Sayuri Matsuoka, Mitsuhiro Furuse, Shigekazu Higuchi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 L-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before L-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of L-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: L-Serine administration enhanced light-induced phase shifts inmice (1.86-fold; P < 0.05). Both L-serine and its metabolite D-serine, a coagonist of N-methyl-D-aspartic acid (NMDA) receptors, exerted this effect, but D-serine concentrations in the hypothalamus did not increase after L-serine administration. The effect of L-serine was blocked by picrotoxin, an antagonist of γ-aminobutyric acid A receptors, but not by MK801, an antagonist of NMDA receptors. L-Serine administration altered the long-term expression patterns of clock genes in the suprachiasmatic nuclei. After advancing the light-dark cycle by 6 h, L-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, L-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-L-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P < 0.05). Conclusion: These results suggest that L-serine enhances light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances.

Original languageEnglish
Pages (from-to)2347-2355
Number of pages9
JournalJournal of Nutrition
Volume147
Issue number12
DOIs
Publication statusPublished - Dec 1 2017

Fingerprint

Serine
Light
Circadian Clocks
N-Methylaspartate
Melatonin
Eating
Aminobutyrates
Amino Acids
Food
Picrotoxin
Inbred CBA Mouse
Suprachiasmatic Nucleus
Photoperiod
Saliva
Running
Hypothalamus
Neurotransmitter Agents
Placebos
Students

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

L-serine enhances light-induced circadian phase resetting in mice and humans. / Yasuo, Shinobu; Iwamoto, Ayaka; Lee, Sang Il; Ochiai, Shotaro; Hitachi, Rina; Shibata, Satomi; Uotsu, Nobuo; Tarumizu, Chie; Matsuoka, Sayuri; Furuse, Mitsuhiro; Higuchi, Shigekazu.

In: Journal of Nutrition, Vol. 147, No. 12, 01.12.2017, p. 2347-2355.

Research output: Contribution to journalArticle

Yasuo, S, Iwamoto, A, Lee, SI, Ochiai, S, Hitachi, R, Shibata, S, Uotsu, N, Tarumizu, C, Matsuoka, S, Furuse, M & Higuchi, S 2017, 'L-serine enhances light-induced circadian phase resetting in mice and humans', Journal of Nutrition, vol. 147, no. 12, pp. 2347-2355. https://doi.org/10.3945/jn.117.255380
Yasuo, Shinobu ; Iwamoto, Ayaka ; Lee, Sang Il ; Ochiai, Shotaro ; Hitachi, Rina ; Shibata, Satomi ; Uotsu, Nobuo ; Tarumizu, Chie ; Matsuoka, Sayuri ; Furuse, Mitsuhiro ; Higuchi, Shigekazu. / L-serine enhances light-induced circadian phase resetting in mice and humans. In: Journal of Nutrition. 2017 ; Vol. 147, No. 12. pp. 2347-2355.
@article{a8f5ec4a622740de9284dc10076777f5,
title = "L-serine enhances light-induced circadian phase resetting in mice and humans",
abstract = "Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 L-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before L-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of L-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: L-Serine administration enhanced light-induced phase shifts inmice (1.86-fold; P < 0.05). Both L-serine and its metabolite D-serine, a coagonist of N-methyl-D-aspartic acid (NMDA) receptors, exerted this effect, but D-serine concentrations in the hypothalamus did not increase after L-serine administration. The effect of L-serine was blocked by picrotoxin, an antagonist of γ-aminobutyric acid A receptors, but not by MK801, an antagonist of NMDA receptors. L-Serine administration altered the long-term expression patterns of clock genes in the suprachiasmatic nuclei. After advancing the light-dark cycle by 6 h, L-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, L-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-L-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P < 0.05). Conclusion: These results suggest that L-serine enhances light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances.",
author = "Shinobu Yasuo and Ayaka Iwamoto and Lee, {Sang Il} and Shotaro Ochiai and Rina Hitachi and Satomi Shibata and Nobuo Uotsu and Chie Tarumizu and Sayuri Matsuoka and Mitsuhiro Furuse and Shigekazu Higuchi",
year = "2017",
month = "12",
day = "1",
doi = "10.3945/jn.117.255380",
language = "English",
volume = "147",
pages = "2347--2355",
journal = "Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "12",

}

TY - JOUR

T1 - L-serine enhances light-induced circadian phase resetting in mice and humans

AU - Yasuo, Shinobu

AU - Iwamoto, Ayaka

AU - Lee, Sang Il

AU - Ochiai, Shotaro

AU - Hitachi, Rina

AU - Shibata, Satomi

AU - Uotsu, Nobuo

AU - Tarumizu, Chie

AU - Matsuoka, Sayuri

AU - Furuse, Mitsuhiro

AU - Higuchi, Shigekazu

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 L-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before L-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of L-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: L-Serine administration enhanced light-induced phase shifts inmice (1.86-fold; P < 0.05). Both L-serine and its metabolite D-serine, a coagonist of N-methyl-D-aspartic acid (NMDA) receptors, exerted this effect, but D-serine concentrations in the hypothalamus did not increase after L-serine administration. The effect of L-serine was blocked by picrotoxin, an antagonist of γ-aminobutyric acid A receptors, but not by MK801, an antagonist of NMDA receptors. L-Serine administration altered the long-term expression patterns of clock genes in the suprachiasmatic nuclei. After advancing the light-dark cycle by 6 h, L-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, L-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-L-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P < 0.05). Conclusion: These results suggest that L-serine enhances light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances.

AB - Background: The circadian clock is modulated by the timing of ingestion or food composition, but the effects of specific nutrients are poorly understood. Objective: We aimed to identify the amino acids that modulate the circadian clock and reset the light-induced circadian phase in mice and humans. Methods: Male CBA/N mice were orally administered 1 of 20 L-amino acids, and the circadian and light-induced phase shifts of wheel-running activity were analyzed. Antagonists of several neurotransmitter pathways were injected before L-serine administration, and light-induced phase shifts were analyzed. In addition, the effect of L-serine on the light-induced phase advance was investigated in healthy male students (mean ± SD age 22.2 ± 1.8 y) by using dim-light melatonin onset (DLMO) determined by saliva samples as an index of the circadian phase. Results: L-Serine administration enhanced light-induced phase shifts inmice (1.86-fold; P < 0.05). Both L-serine and its metabolite D-serine, a coagonist of N-methyl-D-aspartic acid (NMDA) receptors, exerted this effect, but D-serine concentrations in the hypothalamus did not increase after L-serine administration. The effect of L-serine was blocked by picrotoxin, an antagonist of γ-aminobutyric acid A receptors, but not by MK801, an antagonist of NMDA receptors. L-Serine administration altered the long-term expression patterns of clock genes in the suprachiasmatic nuclei. After advancing the light-dark cycle by 6 h, L-serine administration slightly accelerated re-entrainment to the shifted cycle. In humans, L-serine ingestion before bedtime induced significantly larger phase advances of DLMO after bright-light exposure during the morning (means ± SEMs-L-serine: 25.9 ± 6.6 min; placebo: 12.1 ± 7.0 min; P < 0.05). Conclusion: These results suggest that L-serine enhances light-induced phase resetting in mice and humans, and it may be useful for treating circadian disturbances.

UR - http://www.scopus.com/inward/record.url?scp=85036520594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85036520594&partnerID=8YFLogxK

U2 - 10.3945/jn.117.255380

DO - 10.3945/jn.117.255380

M3 - Article

C2 - 29070712

AN - SCOPUS:85036520594

VL - 147

SP - 2347

EP - 2355

JO - Journal of Nutrition

JF - Journal of Nutrition

SN - 0022-3166

IS - 12

ER -