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Multi-omics profiling reveals rhythmic liver function shaped by meal timing.

Rongfeng Huang1, Jianghui Chen1, Meiyu Zhou1

  • 1Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Army Medical University, Chongqing, China.

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Summary
This summary is machine-generated.

Meal timing shapes daily rhythms in liver proteomics and lipidomics beyond gene expression. Nutrient availability resets circadian clock regulation of fatty acid metabolism, impacting PERIOD2 phosphorylation.

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Area of Science:

  • Chronobiology
  • Metabolomics
  • Molecular Biology

Background:

  • Post-translational modifications (PTMs) link feeding patterns to daily biological rhythms.
  • The impact of meal timing on diurnal rhythms beyond the transcriptome is not well understood.

Purpose of the Study:

  • To comprehensively profile daily rhythms of the proteome, four PTMs, and lipidome in mouse liver under different meal timing conditions.
  • To investigate how meal timing influences diurnal rhythms and molecular pathways.

Main Methods:

  • Systematic profiling of proteome, phosphorylation, ubiquitylation, succinylation, N-glycosylation, and lipidome in mouse liver.
  • Comparison between day/sleep time-restricted feeding (DRF) and night/wake time-restricted feeding (NRF).
  • Integrative omics analyses to identify key regulatory mechanisms.

Main Results:

  • Robust daily rhythms were observed across proteomic, PTM, and lipidomic layers.
  • Phosphorylation was the most responsive PTM to nutrients, while succinylation was the least.
  • Meal timing resets clock regulation of fatty acid metabolism, evidenced by rhythmic phosphorylation of PERIOD2 at Ser971 (PER2-pSer971).
  • PER2-pSer971 activation by nutrient availability was confirmed in vivo.

Conclusions:

  • Meal timing significantly organizes diurnal rhythms in liver proteome and lipidome.
  • Circadian regulation of fatty acid metabolism, mediated by PER2 phosphorylation, is a key target reset by meal timing.
  • This study provides a comprehensive resource for understanding liver responses to altered feeding schedules.