@article{52e0caa9223149b2aa5a8fe23f3135a3,
title = "Tryptophan metabolism is a physiological integrator regulating circadian rhythms",
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.",
keywords = "Circadian, Metabolism, Systems biology, Tryptophan",
author = "Paul Petrus and Marlene Cervantes and Muntaha Samad and Tomoki Sato and Alina Chao and Shogo Sato and Koronowski, {Kevin B.} and Grace Park and Yasmine Alam and Niklas Mejhert and Seldin, {Marcus M.} and {Monroy Kuhn}, {Jos{\'e} Manuel} and Dyar, {Kenneth A.} and Dominik Lutter and Pierre Baldi and Peter Kaiser and Cholsoon Jang and Paolo Sassone-Corsi",
note = "Funding Information: We thank all members of the Sassone-Corsi lab for helpful discussion and technical assistance. We greatly appreciate Melanie Oakes and Seung-Ah Chung at the UCI Genomics High-Throughput Facility. Furthermore, we thank the committee consisting of faculty in the Department of Biological Chemistry and Microbiology and Molecular Genetics for their support after the passing of P.S.-C. P.P. was funded by The Wenner-Gren Foundations, The Foundation Blanceflor Boncompagni Ludovisi, n{\'e}e Bildt and Tore Nilsson Foundation for Medical Science. M.C. received fellowships from the National Institutes of Health (NIH) (GM117942), the American Heart Association (17PRE33410952), and the UCI School of Medicine Behrens Research Excellence Award. MMS was supported by NIH grants HL138193, DK130640and DK097771. The work of MS and PB was supported by grant NIH GM123558 to PB. Funding for P.S.-C. was provided by the NIH (AG053592, DK114652), a Novo Nordisk Foundation Challenge Grant, and Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (U1233 INSERM, France). C.J. was funded by AASLD Foundation Pinnacle Research Award in Liver Disease, the Edward Mallinckrodt, Jr. Foundation Award, and NIH (AA029124). Funding Information: We thank all members of the Sassone-Corsi lab for helpful discussion and technical assistance. We greatly appreciate Melanie Oakes and Seung-Ah Chung at the UCI Genomics High-Throughput Facility. Furthermore, we thank the committee consisting of faculty in the Department of Biological Chemistry and Microbiology and Molecular Genetics for their support after the passing of P.S.-C. P.P. was funded by The Wenner-Gren Foundations, The Foundation Blanceflor Boncompagni Ludovisi, n{\'e}e Bildt and Tore Nilsson Foundation for Medical Science. M.C. received fellowships from the National Institutes of Health (NIH) ( GM117942 ), the American Heart Association ( 17PRE33410952 ), and the UCI School of Medicine Behrens Research Excellence Award . MMS was supported by NIH grants HL138193 , DK130640 and DK097771 . The work of MS and PB was supported by grant NIH GM123558 to PB. Funding for P.S.-C. was provided by the NIH ( AG053592 , DK114652 ), a Novo Nordisk Foundation Challenge Grant , and Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (U1233 INSERM, France). C.J. was funded by AASLD Foundation Pinnacle Research Award in Liver Disease , the Edward Mallinckrodt, Jr. Foundation Award , and NIH ( AA029124 ). Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = oct,
doi = "10.1016/j.molmet.2022.101556",
language = "English (US)",
volume = "64",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier GmbH",
}