Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks

Kenneth A. Dyar, Dominik Lutter, Anna Artati, Nicholas J. Ceglia, Yu Liu, Danny Armenta, Martin Jastroch, Sandra Schneider, Sara de Mateo, Marlene Cervantes, Serena Abbondante, Paola Tognini, Ricardo Orozco-Solis, Kenichiro Kinouchi, Christina Wang, Ronald Swerdloff, Seba Nadeef, Selma Masri, Pierre Magistretti, Valerio OrlandoEmiliana Borrelli, N. Henriette Uhlenhaut, Pierre Baldi, Jerzy Adamski*, Matthias H. Tschöp, Kristin Eckel-Mahan, Paolo Sassone-Corsi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

Metabolic diseases are often characterized by circadian misalignment in different tissues, yet how altered coordination and communication among tissue clocks relate to specific pathogenic mechanisms remains largely unknown. Applying an integrated systems biology approach, we performed 24-hr metabolomics profiling of eight mouse tissues simultaneously. We present a temporal and spatial atlas of circadian metabolism in the context of systemic energy balance and under chronic nutrient stress (high-fat diet [HFD]). Comparative analysis reveals how the repertoires of tissue metabolism are linked and gated to specific temporal windows and how this highly specialized communication and coherence among tissue clocks is rewired by nutrient challenge. Overall, we illustrate how dynamic metabolic relationships can be reconstructed across time and space and how integration of circadian metabolomics data from multiple tissues can improve our understanding of health and disease. Circadian metabolite profiles of eight different tissues under standard and high-fat diet uncover highly specialized communication and coherence among tissue clocks and how this is rewired by nutrient challenge.

Original languageEnglish (US)
Pages (from-to)1571-1585.e11
JournalCell
Volume174
Issue number6
DOIs
StatePublished - Sep 6 2018

Keywords

  • CircadiOmics
  • circadian rhythms
  • clock
  • high-fat diet
  • metabolism
  • metabolomics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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