Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Greco, Carolina M.
  • dc.contributor.author Welz, Patrick-Simon
  • dc.contributor.author Kumar, Arun
  • dc.contributor.author Vaca-Dempere, Mireia
  • dc.contributor.author Deryagian, Oleg
  • dc.contributor.author Muñoz Cánoves, Pura, 1962-
  • dc.contributor.author Sassone-Corsi, Paolo
  • dc.date.accessioned 2021-11-15T07:32:40Z
  • dc.date.available 2021-11-15T07:32:40Z
  • dc.date.issued 2021
  • dc.description.abstract The mammalian circadian clock, expressed throughout the brain and body, controls daily metabolic homeostasis. Clock function in peripheral tissues is required, but not sufficient, for this task. Because of the lack of specialized animal models, it is unclear how tissue clocks interact with extrinsic signals to drive molecular oscillations. Here, we isolated the interaction between feeding and the liver clock by reconstituting Bmal1 exclusively in hepatocytes (Liver-RE), in otherwise clock-less mice, and controlling timing of food intake. We found that the cooperative action of BMAL1 and the transcription factor CEBPB regulates daily liver metabolic transcriptional programs. Functionally, the liver clock and feeding rhythm are sufficient to drive temporal carbohydrate homeostasis. By contrast, liver rhythms tied to redox and lipid metabolism required communication with the skeletal muscle clock, demonstrating peripheral clock cross-talk. Our results highlight how the inner workings of the clock system rely on communicating signals to maintain daily metabolism.
  • dc.description.sponsorship C.M.G. was supported by the National Cancer Institute of the National Institutes of Health (NIH) under award number T32CA009054 and by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 749869. K.B.K. was supported by NIH-NINDS F32DK121425, and J.G.S. was supported by the Zymo-CEM Postdoctoral Fellowship (Zymo Research). P.P. was supported by a scholarship from the Wenner-Gren Foundations. C.V. and M.M.S. are supported by NIH grants DK20AU4084 and HL138193.The work of S.C., M.S., and P.B. was in part supported by NIH grant GM123558 to P.B. Work in the W.L. laboratory was supported by NIH grants R01HG007538, R01CA193466, and R01CA228140. Work in the P.S.-C. laboratory is supported by NIH grants R21DK114652 and R21AG053592, a Challenge Grant from the Novo Nordisk Foundation (NNF-202585), and through access to the Genomics High Throughput Facility Shared Resource of the Cancer Center Support Grant (CA-62203) at the UCI and NIH-shared instrumentation grants 1S10RR025496-01, 1S10OD010794-01, and 1S10OD021718-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. P.-S.W. is supported by a “Ramon y Cajal” contract (RYC2019-026661-I) from the Spanish Ministry of Science and Innovation (MICINN). Research in the P.M.-C. laboratory is supported by MINECO-Spain (RTI2018-096068), ERC-2016-AdG-741966, AFM, MDA-USA, La Marató/TV3 Foundation, LaCaixa-HEALTH-HR17-00040, and UPGRADE-H2020-825825 and María-de-Maeztu-Program for Units of Excellence to UPF (MDM-2014-0370) and Severo-Ochoa-Program for Centers of Excellence to CNIC (SEV-2015-0505). Research in the S.A.B. laboratory is supported by the European Research Council (ERC), the Government of Cataluña (SGR grant), the Government of Spain (MINECO), the La Marató/TV3 Foundation, and The Worldwide Cancer Research Foundation (WCRF). Author contributions: C.M.G., K.B.K., J.G.S., P.B., S.M., S.A.B., P.M.-C., and P.S.-C. conceived and designed the study. C.M.G., K.B.K., J.G.S., S.A.B., P.M.-C., and P.S.-C. wrote and edited the manuscript. C.M.G., K.B.K., J.G.S., P.-S.W., V.M.Z., T.M., K.S., T.S., P.P., S.K.C., and K.A.D. performed experiments. O.D., A.K. and M.V.-D. provided technical support. D.L., J.M.M.K., C.V., and M.M.S. performed bioinformatic correlation analyses. S.C., M.S., P.K., R.C., J.S., and W.L. performed sequencing analysis.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Greco CM, Koronowski KB, Smith JG, Shi J, Kunderfranco P, Carriero R et al. Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms. Sci Adv. 2021;7(39):eabi7828. DOI: 10.1126/sciadv.abi7828
  • dc.identifier.doi http://dx.doi.org/10.1126/sciadv.abi7828
  • dc.identifier.issn 2375-2548
  • dc.identifier.uri http://hdl.handle.net/10230/48973
  • dc.language.iso eng
  • dc.publisher American Association for the Advancement of Science (AAAS)
  • dc.relation.ispartof Sci Adv. 2021;7(39):eabi7828
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/749869
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/741966
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825825
  • dc.rights Copyright © 2021 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).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
  • dc.title Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Departament de Medicina i Ciències de la Vida)
Articles (Hospital del Mar Research Institute)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)