ArticleCell metabolism2017
Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism.
Erratum issuedOpen access · bronzeAbstract read
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Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 98 papers.
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98citing papers in PubMed
11.4field-weighted citation impact, top 1% of its field
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Who cites it
98 citing papers in PubMed, 207 citations in OpenAlex.
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- Short-term methionine starvation induces de novo diurnal oscillations of hepatic m6A RNA methylation.bioRxiv : the preprint server for biology · 2026Article
- Glucose is dynamically regulated by time of day in humans and Drosophila.PLoS biology · 2026Article
- Increased Glycine-N-methyltransferase expression disrupts light-dependent gene expression rhythms in the Drosophila eye.Journal of cell science · 2026Article
- Circadian Clock Genes in Colorectal Cancer: From Molecular Mechanisms to Chronotherapeutic Applications.Biomedicines · 2026Review
- Effects of endurance exercise on skeletal muscle and liver metabolic health in male rats with different fitness under chronic circadian rhythm disruption.Frontiers in endocrinology · 2026Article
- Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration.Nature communications · 2025Article
- Circadian Regulation of Neuronal Membrane Capacitance-Mechanisms and Implications for Neural Computation and Behavior.International journal of molecular sciences · 2025Review
- Improved Eggshell Quality in Aged Hens Through Circadian Gut Microbiota and Metabolite Changes Induced by a 28-h Ahemeral Light Cycle.Animals : an open access journal from MDPI · 2025Article
- Multifaceted dynamics of circadian timing system influence aging and longevity.Biogerontology · 2025Review
- Circadian ontogenetic metabolomics atlas: an interactive resource with insights from rat plasma, tissues, and feces.Cellular and molecular life sciences : CMLS · 2025Article
- Circadian rhythm and aryl hydrocarbon receptor crosstalk in bone marrow adipose tissue and implications in leukemia.Scientific reports · 2025Article
- IRF8 aggravates nonalcoholic fatty liver disease via BMAL1/PPARγ axis.Genes & diseases · 2025Article
- Circadian rhythm, epigenetics and disease interaction.Global medical genetics · 2025Review
- Alterations in Circadian Rhythms, Sleep, and Physical Activity in COVID-19: Mechanisms, Interventions, and Lessons for the Future.Molecular neurobiology · 2024Review
- Impact of Modern Lifestyle on Circadian Health and Its Contribution to Adipogenesis and Cancer Risk.Cancers · 2024Review
- When Do Tumours Develop? Neoplastic Processes Across Different Timescales: Age, Season and Round the Circadian Clock.Evolutionary applications · 2024Review
- Glucose Challenge Uncovers Temporal Fungibility of Metabolic Homeostasis over a day:night cycle.bioRxiv : the preprint server for biology · 2024Article
- Chrono-tailored drug delivery systems: recent advances and future directions.Drug delivery and translational research · 2024Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
23 authors at 7 institutions in 2 countries.
Saikumari Y KrishnaiahDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gang WuDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Brian J AltmanAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jacqueline GroweDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Seth D RhoadesDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Faith ColdrenInstitute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Anand VenkataramanDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Anthony O Olarerin-GeorgeDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lauren J FranceyDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Sarmistha MukherjeeDepartment of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Saiveda GirishDepartment of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Christopher P SelbyDepartment of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Sibel CalChemical and Biological Engineering and Molecular Biology and Genetics, Koc University, Rumeli Feneri Yolu, 34450 Sariyer, Istanbul, Turkey.
Ubeydullah ErDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Bahareh SianatiDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Arjun SenguptaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ron C AnafiDepartment of Medicine and Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
I Halil KavakliChemical and Biological Engineering and Molecular Biology and Genetics, Koc University, Rumeli Feneri Yolu, 34450 Sariyer, Istanbul, Turkey.
Aziz SancarDepartment of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Joseph A BaurDepartment of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Chi V DangAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
John B HogeneschDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: john.hogenesch@cchmc.org.
Aalim M WeljieDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: aalim@mail.med.upenn.edu.
Translational Therapeutics (United States) · USCincinnati Children's Hospital Medical Center · USUniversity of Pennsylvania · USCancer Research Institute · USKoç University · TRUniversity of North Carolina at Chapel Hill · USCircadian (United States) · US
Funding
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5MInstitutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9MTranslational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca A Simmons · 2006 to 2026
$35.3MMolecular Mechanism of Mammalian DNA Excision Repair, DNA Damage Checkpoints and the Circadian ClockR35GM118102 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI AZIZ SANCAR · 2016 to 2026
$10.6MC-MYC TARGETS IN THE PATHOGENESIS OF HUMAN CANCERSR01CA057341 · NCI · WISTAR INSTITUTE · PI DANG, CHI V. · 1992 to 2021
$8.3MMolecular, Cellular and Physiological Mechanisms of the Mammalian Circadian ClockR01NS054794 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI HOGENESCH, JOHN B, LIU, ANDREW C. · 2007 to 2022
$8.1MTargeting NAD Metabolism to Improve Glucose Homeostasis in Obesity and AgingR01DK098656 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Joseph A. Baur · 2013 to 2026
$6.1MMYC--TRANSCRIPTION AND INTERACTION WITH P107R01CA051497 · NCI · WISTAR INSTITUTE · PI DANG, CHI V. · 1995 to 2025
$5.3MSTRUCTURE/FUNCTION OF DNA PHOTOLYASER01GM031082 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SANCAR, AZIZ · 1985 to 2015
$4.9MDefining metabolic adaptations within the PDAC "arid" tumor microenvironmentR01CA252225 · NCI · WISTAR INSTITUTE · PI DANG, CHI V., STANGER, BEN Z · 2021 to 2025
$2.8MMolecular Mechanisms of Rapamycin's Effects on Health and LongevityR01AG043483 · NIA · UNIVERSITY OF PENNSYLVANIA · PI BAUR, JOSEPH A. · 2013 to 2017
$2.0MOncogenic Disruption of the Circadian Metabolic Cycle in CancerK99CA204593 · NCI · WISTAR INSTITUTE · PI ALTMAN, BRIAN JAMES · 2016 to 2017
$173kNCATS NIH HHS UL1 TR000003NCI NIH HHS F32 CA180370NCI NIH HHS K99 CA204593NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA051497NCI NIH HHS R01 CA057341NCI NIH HHS R01 CA252225NIA NIH HHS R01 AG043483NIDDK NIH HHS R01 DK098656NIEHS NIH HHS P30 ES013508NIGMS NIH HHS R01 GM031082NIGMS NIH HHS R35 GM118102NINDS NIH HHS R01 NS054794
Abstract
The intricate connection between the circadian clock and metabolism remains poorly understood. We used high temporal resolution metabolite profiling to explore clock regulation of mouse liver and cell-autonomous metabolism. In liver, ∼50% of metabolites were circadian, with enrichment of nucleotide, amino acid, and methylation pathways. In U2 OS cells, 28% were circadian, including amino acids and NAD biosynthesis metabolites. Eighteen metabolites oscillated in both systems and a subset of these in primary hepatocytes. These 18 metabolites were enriched in methylation and amino acid pathways. To assess clock dependence of these rhythms, we used genetic perturbation. BMAL1 knockdown diminished metabolite rhythms, while CRY1 or CRY2 perturbation generally shortened or lengthened rhythms, respectively. Surprisingly, CRY1 knockdown induced 8 hr rhythms in amino acid, methylation, and vitamin metabolites, decoupling metabolite from transcriptional rhythms, with potential impact on nutrient sensing in vivo. These results provide the first comprehensive views of circadian liver and cell-autonomous metabolism.
Indexed as
Transcription, GeneticAnimalsCell Line, TumorCells, CulturedCircadian ClocksCircadian RhythmCreatineCryptochromesGene Regulatory NetworksHepatocytesHumansLiverMetabolomeMiceNitrogenTime FactorsCreatineCryptochromesNitrogenchronometabolismchronopharmacologycircadian clockcircadian metabolismLCMSmass spectrometrymetabolomicstranslational transcription feedback loop
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