Diurnal Transcriptome Landscape of a Multi-tissue Response to Time-restricted Feeding in Mammals

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2023 Jan 4

PMID 36599299

Authors

Shaunak Deota

Terry Lin

Amandine Chaix

April Williams

Hiep Le

Hugo Calligaro

Ramesh Ramasamy

Ling Huang

Satchidananda Panda

Affiliations

Soon will be listed here.

Abstract

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.

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References

Weger B, Gobet C, David F, Atger F, Martin E, Phillips N . Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms. Proc Natl Acad Sci U S A. 2021; 118(3). PMC: 7826335. DOI: 10.1073/pnas.2015803118. View

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

Yeung J, Mermet J, Jouffe C, Marquis J, Charpagne A, Gachon F . Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs. Genome Res. 2017; 28(2):182-191. PMC: 5793782. DOI: 10.1101/gr.222430.117. View

Wilson K, Chamoli M, Hilsabeck T, Pandey M, Bansal S, Chawla G . Evaluating the beneficial effects of dietary restrictions: A framework for precision nutrigeroscience. Cell Metab. 2021; 33(11):2142-2173. PMC: 8845500. DOI: 10.1016/j.cmet.2021.08.018. View

Lynch C, Adams S . Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol. 2014; 10(12):723-36. PMC: 4424797. DOI: 10.1038/nrendo.2014.171. View

Patel S, Velingkaar N, Makwana K, Chaudhari A, Kondratov R . Calorie restriction regulates circadian clock gene expression through BMAL1 dependent and independent mechanisms. Sci Rep. 2016; 6:25970. PMC: 4864379. DOI: 10.1038/srep25970. View

Zhang R, Podtelezhnikov A, Hogenesch J, Anafi R . Discovering Biology in Periodic Data through Phase Set Enrichment Analysis (PSEA). J Biol Rhythms. 2016; 31(3):244-57. DOI: 10.1177/0748730416631895. View

Derous D, Mitchell S, Wang L, Green C, Wang Y, Chen L . The effects of graded levels of calorie restriction: XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome. Aging (Albany NY). 2017; 9(7):1770-1824. PMC: 5559174. DOI: 10.18632/aging.101269. View

Mure L, Le H, Benegiamo G, Chang M, Rios L, Jillani N . Diurnal transcriptome atlas of a primate across major neural and peripheral tissues. Science. 2018; 359(6381). PMC: 5924732. DOI: 10.1126/science.aao0318. View

10.

Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong E, Gill S . Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012; 15(6):848-60. PMC: 3491655. DOI: 10.1016/j.cmet.2012.04.019. View

11.

Acosta-Rodriguez V, Rijo-Ferreira F, Green C, Takahashi J . Importance of circadian timing for aging and longevity. Nat Commun. 2021; 12(1):2862. PMC: 8129076. DOI: 10.1038/s41467-021-22922-6. View

12.

McCarthy D, Chen Y, Smyth G . Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 2012; 40(10):4288-97. PMC: 3378882. DOI: 10.1093/nar/gks042. View

13.

Acosta-Rodriguez V, Rijo-Ferreira F, Izumo M, Xu P, Wight-Carter M, Green C . Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice. Science. 2022; 376(6598):1192-1202. PMC: 9262309. DOI: 10.1126/science.abk0297. View

14.

Hatchwell L, Harney D, Cielesh M, Young K, Koay Y, OSullivan J . Multi-omics Analysis of the Intermittent Fasting Response in Mice Identifies an Unexpected Role for HNF4α. Cell Rep. 2020; 30(10):3566-3582.e4. DOI: 10.1016/j.celrep.2020.02.051. View

15.

Smith R, Soeters M, Wust R, Houtkooper R . Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease. Endocr Rev. 2018; 39(4):489-517. PMC: 6093334. DOI: 10.1210/er.2017-00211. View

16.

Liao Y, Wang J, Jaehnig E, Shi Z, Zhang B . WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res. 2019; 47(W1):W199-W205. PMC: 6602449. DOI: 10.1093/nar/gkz401. View

17.

Vollmers C, Gill S, DiTacchio L, Pulivarthy S, Le H, Panda S . Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. Proc Natl Acad Sci U S A. 2009; 106(50):21453-8. PMC: 2795502. DOI: 10.1073/pnas.0909591106. View

18.

Green C, Lamming D, Fontana L . Molecular mechanisms of dietary restriction promoting health and longevity. Nat Rev Mol Cell Biol. 2021; 23(1):56-73. PMC: 8692439. DOI: 10.1038/s41580-021-00411-4. View

19.

Acosta-Rodriguez V, de Groot M, Rijo-Ferreira F, Green C, Takahashi J . Mice under Caloric Restriction Self-Impose a Temporal Restriction of Food Intake as Revealed by an Automated Feeder System. Cell Metab. 2017; 26(1):267-277.e2. PMC: 5576447. DOI: 10.1016/j.cmet.2017.06.007. View

20.

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View