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

Rongfeng Huang, Jianghui Chen, Meiyu Zhou, Haoran Xin, Sin Man Lam, Xiaoqing Jiang, Jie Li, Fang Deng, Guanghou Shui, Zhihui Zhang () and Min-Dian Li ()
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Rongfeng Huang: Army Medical University
Jianghui Chen: Army Medical University
Meiyu Zhou: Army Medical University
Haoran Xin: Army Medical University
Sin Man Lam: Chinese Academy of Sciences
Xiaoqing Jiang: Army Medical University
Jie Li: Army Medical University
Fang Deng: Army Medical University
Guanghou Shui: Chinese Academy of Sciences
Zhihui Zhang: Army Medical University
Min-Dian Li: Army Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Post-translational modifications (PTMs) couple feed-fast cycles to diurnal rhythms. However, it remains largely uncharacterized whether and how meal timing organizes diurnal rhythms beyond the transcriptome. Here, we systematically profile the daily rhythms of the proteome, four PTMs (phosphorylation, ubiquitylation, succinylation and N-glycosylation) and the lipidome in the liver from young female mice subjected to either day/sleep time-restricted feeding (DRF) or night/wake time-restricted feeding (NRF). We detect robust daily rhythms among different layers of omics with phosphorylation the most nutrient-responsive and succinylation the least. Integrative analyses reveal that clock regulation of fatty acid metabolism represents a key diurnal feature that is reset by meal timing, as indicated by the rhythmic phosphorylation of the circadian repressor PERIOD2 at Ser971 (PER2-pSer971). We confirm that PER2-pSer971 is activated by nutrient availability in vivo. Together, this dataset represents a comprehensive resource detailing the proteomic and lipidomic responses by the liver to alterations in meal timing.

Date: 2023
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DOI: 10.1038/s41467-023-41759-9

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