Lipid molecular timeline profiling reveals diurnal crosstalk between the liver and circulation

Richard R. Sprenger, Martin Hermansson, Ditte Neess, Lena Sokol Becciolini, Signe Bek Sørensen, Rolf Fagerberg, Josef Ecker, Gerhard Liebisch, Ole N. Jensen, Dennis E. Vance, Nils J. Færgeman, Robin W. Klemm, Christer S. Ejsing*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Diurnal regulation of whole-body lipid metabolism plays a vital role in metabolic health. Although changes in lipid levels across the diurnal cycle have been investigated, the system-wide molecular responses to both short-acting fasting-feeding transitions and longer-timescale circadian rhythms have not been explored in parallel. Here, we perform time-series multi-omics analyses of liver and plasma revealing that the majority of molecular oscillations are entrained by adaptations to fasting, food intake, and the postprandial state. By developing algorithms for lipid structure enrichment analysis and lipid molecular crosstalk between tissues, we find that the hepatic phosphatidylethanolamine (PE) methylation pathway is diurnally regulated, giving rise to two pools of oscillating phosphatidylcholine (PC) molecules in the circulation, which are coupled to secretion of either very low-density lipoprotein (VLDL) or high-density lipoprotein (HDL) particles. Our work demonstrates that lipid molecular timeline profiling across tissues is key to disentangling complex metabolic processes and provides a critical resource for the study of whole-body lipid metabolism.
Original languageEnglish
Article number108710
JournalCell Reports
Volume34
Issue number5
Number of pages23
ISSN2211-1247
DOIs
Publication statusPublished - 2. Feb 2021

Keywords

  • blood plasma
  • circadian rhythm
  • diurnal regulation
  • fasting-feeding cycles
  • lipidomics
  • lipoprotein particles
  • liver
  • PE methylation pathway
  • Pemt
  • proteomics

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