Cell Metabolism
Volume 35, Issue 1, 3 January 2023, Pages 150-165.e4
Journal home page for Cell Metabolism

Article
Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals

https://doi.org/10.1016/j.cmet.2022.12.006Get rights and content
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open access

Highlights

  • 80% of genes are differentially expressed or rhythmic under TRF in at least one tissue

  • TRF decreases genes involved in inflammatory signaling and glycerolipid metabolism

  • TRF increases genes involved in RNA processing, protein folding, and autophagy

  • TRF causes multi-tissue rewiring of BCAA, glucose, and lipid metabolism

Summary

Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention that involves a daily cycle of feeding and fasting. In both animals and humans, TRF has pleiotropic health benefits that arise from multiple organ systems, yet the molecular basis of TRF-mediated benefits is not well understood. Here, we subjected mice to isocaloric ad libitum feeding (ALF) or TRF of a western diet and examined gene expression changes in samples taken from 22 organs and brain regions collected every 2 h over a 24-h period. We discovered that TRF profoundly impacts gene expression. Nearly 80% of all genes show differential expression or rhythmicity under TRF in at least one tissue. Functional annotation of these changes revealed tissue- and pathway-specific impacts of TRF. These findings and resources provide a critical foundation for future mechanistic studies and will help to guide human time-restricted eating (TRE) interventions to treat various disease conditions with or without pharmacotherapies.

Keywords

time-restricted feeding
circadian clock
feeding-fasting rhythms
metabolic syndrome
metabolic flexibility
multi-tissue transcriptomics
hepatic metabolomics

Data and code availability

  • All the bulk RNA-seq data have been deposited at GEO and are publicly available as of the date of publication. Accession numbers are listed in the key resources table. Files containing TMM normalized counts, statistical analyses for differential and rhythmic gene expression, and liver metabolome counts and statistical analyses have been deposited at Mendeley data and are publicly available as of the date of publication. The DOI is listed in the key resources table.

  • This paper does not report original code.

  • All values used to generate the graphs of the paper can be found in the file Data S1 – Source Data. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

2

Present address: Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT 84112, USA

3

Lead contact