Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice

Cell Rep. 2019 Apr 16;27(3):649-657.e5. doi: 10.1016/j.celrep.2019.03.064.


Every mammalian tissue exhibits daily rhythms in gene expression to control the activation of tissue-specific processes at the most appropriate time of the day. Much of this rhythmic expression is thought to be driven cell autonomously by molecular circadian clocks present throughout the body. By manipulating the daily rhythm of food intake in the mouse, we here show that more than 70% of the cycling mouse liver transcriptome loses rhythmicity under arrhythmic feeding. Remarkably, core clock genes are not among the 70% of genes losing rhythmic expression, and their expression continues to exhibit normal oscillations in arrhythmically fed mice. Manipulation of rhythmic food intake also alters the timing of key signaling and metabolic pathways without altering the hepatic clock oscillations. Our findings thus demonstrate that systemic signals driven by rhythmic food intake significantly contribute to driving rhythms in liver gene expression and metabolic functions independently of the cell-autonomous hepatic clock.

Keywords: RNA-seq; biological rhythms; circadian clock; feeding behavior; lipogenesis; liver; mTOR; mouse; temporal restricted feeding; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / deficiency
  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism
  • Animals
  • Behavior, Animal
  • Blood Glucose / analysis
  • Circadian Clocks / genetics*
  • Eating*
  • Gene Expression Regulation
  • Insulin / administration & dosage
  • Lipogenesis
  • Liver / metabolism*
  • Male
  • Metabolic Networks and Pathways / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • TOR Serine-Threonine Kinases / metabolism


  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Blood Glucose
  • Insulin
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3