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J Nutr. 2017 Dec;147(12):2347-2355. doi: 10.3945/jn.117.255380. Epub 2017 Oct 25.

l-Serine Enhances Light-Induced Circadian Phase Resetting in Mice and Humans.

Author information

1
Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, and syasuo@brs.kyushu-u.ac.jp.
2
Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, and.
3
Department of Human Science, Faculty of Design, Kyushu University, Fukuoka, Japan; and.
4
Health Science Research Center, Research Institute, FANCL Co., Yokohama, Japan.

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 in mice (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.

KEYWORDS:

GABA receptor; NMDA receptor; amino acids; chrononutrition; circadian clock; clock genes; dim-light melatonin onset

PMID:
29070712
DOI:
10.3945/jn.117.255380
[Indexed for MEDLINE]

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