Tryptophan metabolism is a physiological integrator regulating circadian rhythms

Paul Petrus, Marlene Cervantes, Muntaha Samad, Tomoki Sato, Alina Chao, Shogo Sato, Kevin B. Koronowski, Grace Park, Yasmine Alam, Niklas Mejhert, Marcus M. Seldin, José Manuel Monroy Kuhn, Kenneth A. Dyar, Dominik Lutter, Pierre Baldi, Peter Kaiser, Cholsoon Jang, Paolo Sassone-Corsi

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number101556
JournalMolecular Metabolism
Volume64
DOIs
StatePublished - Oct 2022
Externally publishedYes

Keywords

  • Circadian
  • Metabolism
  • Systems biology
  • Tryptophan

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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