@article{c27d789f487f45e6a7268b9a08b88d36,
title = "Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism",
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.",
keywords = "LCMS, chronometabolism, chronopharmacology, circadian clock, circadian metabolism, mass spectrometry, metabolomics, translational transcription feedback loop",
author = "Krishnaiah, {Saikumari Y.} and Gang Wu and Altman, {Brian J.} and Jacqueline Growe and Rhoades, {Seth D.} and Faith Coldren and Anand Venkataraman and Olarerin-George, {Anthony O.} and Francey, {Lauren J.} and Sarmistha Mukherjee and Saiveda Girish and Selby, {Christopher P.} and Sibel Cal and Ubeydullah ER and Bahareh Sianati and Arjun Sengupta and Anafi, {Ron C.} and Kavakli, {I. Halil} and Aziz Sancar and Baur, {Joseph A.} and Dang, {Chi V.} and Hogenesch, {John B.} and Weljie, {Aalim M.}",
note = "Funding Information: We thank Nick Lahens for providing U2 OS transcriptomic cycling numbers, Barry Slaff for assistance in collection of circadian cell culture samples, and Alyssa Kriegermeier for assistance in mouse primary hepatocyte collection protocol. This work is supported by the National Institute of Neurological Disorders and Stroke (5R01NS054794-08 to J.B.H.), the Defense Advanced Research Projects Agency (DARPA-D12AP00025 to John Harer, Duke University), a TAPITMAT award to A.M.W. via the National Center for Advancing Translational Sciences (5UL1TR000003 to Garret Fitzgerald), the National Cancer Institute (NCI) of the NIH K99CA204593 (to B.J.A.) and R01CA057341 (to C.V.D.), the Leukemia and Lymphoma Society LLS 6106-14 (to C.V.D.), the Abramson Family Cancer Research Institute (to C.V.D.), the National Institute for Diabetes and Digestive and Kidneys Diseases (R01DK098656 to J.A.B.), the National Institute on Aging (R01AG043483 to J.A.B.), and the Penn Genome Frontiers Institute under an HRFF grant with the Pennsylvania Department of Health. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = apr,
day = "4",
doi = "10.1016/j.cmet.2017.03.019",
language = "English (US)",
volume = "25",
pages = "961--974.e4",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",
}