Impact of Bmal1 rescue and time-restricted feeding on liver and muscle proteomes during the active phase in mice

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• dc.contributor.author Smith, Jacob G.
• dc.contributor.author Molendijk, Jeffrey
• dc.contributor.author Blazev, Ronnie
• dc.contributor.author Chen, Wan Hsi
• dc.contributor.author Zhang, Qing
• dc.contributor.author Litwin, Christopher
• dc.contributor.author Zinna, Valentina M.
• dc.contributor.author Welz, Patrick-Simon
• dc.contributor.author Aznar Benitah, Salvador
• dc.contributor.author Greco, Carolina M.
• dc.contributor.author Sassone-Corsi, Paolo
• dc.contributor.author Muñoz Cánoves, Pura, 1962-
• dc.contributor.author Parker, Benjamin L.
• dc.contributor.author Koronowski, Kevin B.
• dc.date.accessioned 2024-02-05T15:49:46Z
• dc.date.available 2024-02-05T15:49:46Z
• dc.date.issued 2023
• dc.description.abstract Molecular clocks and daily feeding cycles support metabolism in peripheral tissues. Although the roles of local clocks and feeding are well defined at the transcriptional level, their impact on governing protein abundance in peripheral tissues is unclear. Here, we determine the relative contributions of local molecular clocks and daily feeding cycles on liver and muscle proteomes during the active phase in mice. LC-MS/MS was performed on liver and gastrocnemius muscle harvested 4 h into the dark phase from WT, Bmal1 KO, and dual liver- and muscle-Bmal1-rescued mice under either ad libitum feeding or time-restricted feeding during the dark phase. Feeding-fasting cycles had only minimal effects on levels of liver proteins and few, if any, on the muscle proteome. In contrast, Bmal1 KO altered the abundance of 674 proteins in liver and 80 proteins in muscle. Local rescue of liver and muscle Bmal1 restored ∼50% of proteins in liver and ∼25% in muscle. These included proteins involved in fatty acid oxidation in liver and carbohydrate metabolism in muscle. For liver, proteins involved in de novo lipogenesis were largely dependent on Bmal1 function in other tissues (i.e., the wider clock system). Proteins regulated by BMAL1 in liver and muscle were enriched for secreted proteins. We found that the abundance of fibroblast growth factor 1, a liver secreted protein, requires BMAL1 and that autocrine fibroblast growth factor 1 signaling modulates mitochondrial respiration in hepatocytes. In liver and muscle, BMAL1 is a more potent regulator of dark phase proteomes than daily feeding cycles, highlighting the need to assess protein levels in addition to mRNA when investigating clock mechanisms. The proteome is more extensively regulated by BMAL1 in liver than in muscle, and many metabolic pathways in peripheral tissues are reliant on the function of the clock system as a whole.
• dc.description.sponsorship The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Work in the B. L. P. laboratory was funded by an NHMRC Emerging Leader Investigator Grant (APP2009642) and a University of Melbourne Driving Research Momentum Grant. C. M. G. was supported by the National Cancer Institute of the National Institutes of Health under award T32CA009054 and by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 749869. P. S. W. was supported by grant RYC2019-026661-I funded by MCIN/AEI/10.13039/501100011033 and by "ESF Investing in your future", grant PID2020-113317RA-I00 funded by MCIN/AEI/ 10.13039/501100011033, and by the BBVA Foundation. Research in the S. A. B. lab 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 MaratóTV3– 80/19-202021, MWRF, and María-de-Maeztu Program for Units of Excellence to UPF (MDM-2014-0370) and the Severo- Ochoa Program for Centers of Excellence to CNIC (SEV2015-0505). Work in the P.S.-C. laboratory was supported by NIH grants R21DK114652 and R21AG053592, a Challenge Grant from the Novo Nordisk Foundation (NNF202585), KAUST funding (OSR-2019-CRG8-URF/1/4042).
• dc.format.mimetype application/pdf
• dc.identifier.citation Smith JG, Molendijk J, Blazev R, Chen WH, Zhang Q, Litwin C, Zinna VM, Welz PS, Benitah SA, Greco CM, Sassone-Corsi P, Muñoz-Cánoves P, Parker BL, Koronowski KB. Impact of Bmal1 rescue and time-restricted feeding on liver and muscle proteomes during the active phase in mice. Mol Cell Proteomics. 2023 Nov;22(11):100655. DOI: 10.1016/j.mcpro.2023.100655
• dc.identifier.doi http://dx.doi.org/10.1016/j.mcpro.2023.100655
• dc.identifier.issn 1535-9476
• dc.identifier.uri http://hdl.handle.net/10230/58954
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Mol Cell Proteomics. 2023 Nov;22(11):100655
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/749869
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RYC2019-026661-I
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-113317RA-I00
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/787041
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-096068
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/741966
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825825
• dc.rights © 2023 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Bmal1
• dc.subject.keyword FGF1
• dc.subject.keyword Circadian clocks
• dc.subject.keyword Circadian rhythms
• dc.subject.keyword Fibroblast growth factor
• dc.subject.keyword Liver
• dc.subject.keyword Muscle
• dc.subject.keyword Time-restricted feeding
• dc.title Impact of Bmal1 rescue and time-restricted feeding on liver and muscle proteomes during the active phase in mice
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion