{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:56:37Z","timestamp":1782280597247,"version":"3.54.5"},"posted":{"date-parts":[[2025,1,20]]},"group-title":"Cell Biology","reference-count":21,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Circadian clocks present throughout the brain and body coordinate diverse physiological processes to support daily homeostasis and respond to changing environmental conditions. The local dependencies within the mammalian clock network are not well defined. We previously demonstrated that the skeletal muscle clock controls transcript oscillations of genes involved in fatty acid metabolism in the liver, yet whether the liver clock also regulates the muscle was unknown. Here, we use hepatocyte-specific\n                  <jats:italic>Bmal1<\/jats:italic>\n                  KO mice (Bmal1\n                  <jats:sup>hep-\/-<\/jats:sup>\n                  ) and reveal that approximately one third of transcriptional rhythms in skeletal muscle are regulated by the liver clock vivo. Treatment of myotubes with serum harvested from\n                  <jats:italic>Bmal1<\/jats:italic>\n                  <jats:sup>hep-\/-<\/jats:sup>\n                  mice inhibited expression of genes involved in metabolic pathways, including oxidative phosphorylation. Overall, the transcriptional changes induced by liver clock-driven endocrine-communication revealed from our in vitro system were small in magnitude, leading us to surmise that the liver clock acts to fine-tune metabolic gene expression in muscle. Strikingly, treatment of myotubes with serum from\n                  <jats:italic>Bmal1<\/jats:italic>\n                  <jats:sup>hep-\/-<\/jats:sup>\n                  mice inhibited mitochondrial ATP production compared to WT and this effect was only observed with serum harvested during the active phase. Overall, our results reveal communication between the liver clock and skeletal muscle\u2013uncovering a bidirectional endocrine communication pathway dependent on clocks in these two key metabolic tissues. Targeting liver and muscle circadian clocks may represent a potential avenue for exploration for diseases associated with dysregulation of metabolism in these tissues.\n                <\/jats:p>","DOI":"10.1101\/2025.01.17.633623","type":"posted-content","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T06:05:19Z","timestamp":1737353119000},"source":"Crossref","is-referenced-by-count":1,"title":["The liver clock tunes transcriptional rhythms in skeletal muscle to regulate mitochondrial function"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2770-5847","authenticated-orcid":false,"given":"Valentina","family":"Sica","sequence":"first","affiliation":[{"name":"Universitat Pompeu Fabra (UPF), Department of Medicine and Life Sciences (MELIS), 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3044-6874","authenticated-orcid":false,"given":"Tomoki","family":"Sato","sequence":"additional","affiliation":[{"name":"Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Tsialtas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Structural Biology, University of Texas Health San Antonio, San Antonio, Texas, 78229, USA"},{"name":"Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, Texas, 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Structural Biology, University of Texas Health San Antonio, San Antonio, Texas, 78229, USA"},{"name":"Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, Texas, 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute for Genomics and Bioinformatics, Department of Computer Science, UCI, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Baldi","sequence":"additional","affiliation":[{"name":"Institute for Genomics and Bioinformatics, Department of Computer Science, UCI, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pura","family":"Mu\u00f1oz C\u00e1noves","sequence":"additional","affiliation":[{"name":"Universitat Pompeu Fabra (UPF), Department of Medicine and Life Sciences (MELIS), 08003 Barcelona, Spain"},{"name":"Catalan Institution for Research and Advanced Studies (ICREA), 08010, Barcelona, Spain"},{"name":"Altos Labs Inc, San Diego Institute of Science, San Diego, CA 92121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Sassone-Corsi","sequence":"additional","affiliation":[{"name":"Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6808-1789","authenticated-orcid":false,"given":"Kevin B.","family":"Koronowski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Structural Biology, University of Texas Health San Antonio, San Antonio, Texas, 78229, USA"},{"name":"Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, Texas, 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5139-1054","authenticated-orcid":false,"given":"Jacob G.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, School of Biology, University of Barcelona, Barcelona, Spain"},{"name":"Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, 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