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Tryptophan metabolism is a physiological integrator regulating circadian rhythms
- Petrus, Paul;
- Cervantes, Marlene;
- Samad, Muntaha;
- Sato, Tomoki;
- Chao, Alina;
- Sato, Shogo;
- Koronowski, Kevin B;
- Park, Grace;
- Alam, Yasmine;
- Mejhert, Niklas;
- Seldin, Marcus M;
- Kuhn, José Manuel Monroy;
- Dyar, Kenneth A;
- Lutter, Dominik;
- Baldi, Pierre;
- Kaiser, Peter;
- Jang, Cholsoon;
- Sassone-Corsi, Paolo
- et al.
Published Web Location
https://doi.org/10.1016/j.molmet.2022.101556Abstract
Objective
The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on the role of essential amino acids.Methods
Mice were fed diets depleted of specific essential amino acids and their behavioral rhythms were monitored and tryptophan was selected for downstream analyses. The role of tryptophan metabolism in modulating circadian homeostasis was studied using isotope tracing as well as transcriptomic- and metabolomic- analyses.Results
Dietary tryptophan depletion alters behavioral rhythms in mice. Furthermore, tryptophan metabolism was shown to be regulated in a time- and light- dependent manner. A multi-omics approach and combinatory diet/light interventions demonstrated that tryptophan metabolism modulates temporal regulation of metabolism and transcription programs by buffering photic cues. Specifically, tryptophan metabolites regulate central circadian functions of the suprachiasmatic nucleus and the core clock machinery in the liver.Conclusions
Tryptophan metabolism is a modulator of circadian homeostasis by integrating environmental cues. Our findings propose tryptophan metabolism as a potential point for pharmacologic intervention to modulate phenotypes associated with disrupted circadian rhythms.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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