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Petrus, P.* ; Cervantes, M.* ; Samad, M.* ; Sato, T.* ; Chao, A.* ; Sato, S.* ; Koronowski, K.B.* ; Park, G.* ; Alam, Y.* ; Mejhert, N.* ; Seldin, M.M.* ; Monroy Kuhn, J.M. ; Dyar, K.A. ; Lutter, D. ; Baldi, P.* ; Kaiser, P.* ; Jang, C.* ; Sassone-Corsi, P.*

Tryptophan metabolism is a physiological integrator regulating circadian rhythms.

Mol. Metab. 64:101556 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Circadian ; Metabolism ; Systems Biology ; Tryptophan
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 64, Heft: , Seiten: , Artikelnummer: 101556 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Institute of Diabetes and Cancer (IDC)