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 language | English |
|---|---|
| Pages (from-to) | 2347-2355 |
| Number of pages | 9 |
| Journal | Journal of Nutrition |
| Volume | 147 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2017 |
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All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Nutrition and Dietetics
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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 journal › Article
}
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 -