The central clock suffices to drive the majority of circulatory metabolic rhythms

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• dc.contributor.author Petrus, Paul
• dc.contributor.author Smith, Jacob G.
• dc.contributor.author Koronowski, Kevin B.
• dc.contributor.author Chen, Siwei
• dc.contributor.author Sato, Tomoki
• dc.contributor.author Greco, Carolina M.
• dc.contributor.author Mortimer, Thomas
• dc.contributor.author Welz, Patrick-Simon
• dc.contributor.author Zinna, Valentina M.
• dc.contributor.author Shimaji, Kohei
• dc.contributor.author Cervantes, Marlene
• dc.contributor.author Punzo, Daniela
• dc.contributor.author Baldi, Pierre
• dc.contributor.author Muñoz Cánoves, Pura, 1962-
• dc.contributor.author Sassone-Corsi, Paolo
• dc.contributor.author Aznar Benitah, Salvador
• dc.date.accessioned 2022-09-09T06:46:20Z
• dc.date.available 2022-09-09T06:46:20Z
• dc.date.issued 2022
• dc.description.abstract Life on Earth anticipates recurring 24-hour environmental cycles via genetically encoded molecular clocks active in all mammalian organs. Communication between these clocks controls circadian homeostasis. Intertissue communication is mediated, in part, by temporal coordination of metabolism. Here, we characterize the extent to which clocks in different organs control systemic metabolic rhythms, an area that remains largely unexplored. We analyzed the metabolome of serum from mice with tissue-specific expression of the clock gene Bmal1. Having functional hepatic and muscle clocks can only drive a minority (13%) of systemic metabolic rhythms. Conversely, limiting Bmal1 expression to the central pacemaker in the brain restores rhythms to 57% of circulatory metabolites. Rhythmic feeding imposed on clockless mice resulted in a similar rescue, indicating that the central clock mainly regulates metabolic rhythms via behavior. These findings explicate the circadian communication between tissues and highlight the importance of the central clock in governing those signals.
• dc.description.sponsorship P.P. was funded by the Wenner-Gren Foundation; the Foundation Blanceflor Boncompagni Ludovisi, née Bildt; and the Tore Nilsson Foundation for Medical Science. Funding for P.S.-C. was provided by the National Institutes of Health (NIH) (AG053592 and DK114652), a Novo Nordisk Foundation Challenge Grant, and Institut National de la Sante et la Recherche Medicale (U1233 INSERM, France). Research in the S.A.B. laboratory is supported partially by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 787041), the Government of Cataluña (SGR grant), the Government of Spain (MINECO), the La Marató/TV3 Foundation, the Foundation Lilliane Bettencourt, the Spanish Association for Cancer Research (AECC), and the Worldwide Cancer Research Foundation (WCRF). The IRB Barcelona is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). P.M.C. acknowledges funding from MICINN-RTI2018-096068, ERC-2016-AdG-741966, LaCaixa-HEALTH-HR17-00040, MDA, UPGRADE-H2020-825825, AFM, DPP-Spain, Fundació La Marató TV3-80/19-202021, MWRF, María-de-Maeztu Program for Units of Excellence to UPF (MDM-2014-0370), and the Severo- Ochoa Program for Centers of Excellence to CNIC (SEV-2015-0505). T.S. was supported by a Japan Society for the Promotion of Science (JSPS) fellowship. C.M.G. was funded by European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 749869. T.M. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754510. P.-S.W. is supported by grant RYC2019-026661-I funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future.” We acknowledge predoctoral fellowships to M.C. from the NIH (GM117942), the American Heart Association (17PRE33410952), and the UCI School of Medicine Behrens Research Excellence Award. The work of S.C. and P.B. was, in part, supported by NIH grant NIH GM123558.
• dc.format.mimetype application/pdf
• dc.identifier.citation Petrus P, Smith JG, Koronowski KB, Chen S, Sato T, Greco CM, Mortimer T, Welz PS, Zinna VM, Shimaji K, Cervantes M, Punzo D, Baldi P, Muñoz-Cánoves P, Sassone-Corsi P, Aznar Benitah S. The central clock suffices to drive the majority of circulatory metabolic rhythms. Sci Adv. 2022 Jul;8(26):eabo2896. DOI: 10.1126/sciadv.abo2896
• dc.identifier.doi http://dx.doi.org/10.1126/sciadv.abo2896
• dc.identifier.issn 2375-2548
• dc.identifier.uri http://hdl.handle.net/10230/54033
• dc.language.iso eng
• dc.publisher American Association for the Advancement of Science (AAAS)
• dc.relation.ispartof Sci Adv. 2022 Jul;8(26):eabo2896
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/787041
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/741966
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825825
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/749869
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/754510
• dc.rights © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
• dc.title The central clock suffices to drive the majority of circulatory metabolic rhythms
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion