Diurnal variation in gene expression of human peripheral blood mononuclear cells after eating a standard meal compared with a high protein meal: A cross-over study

Clin Nutr. 2021 Jun;40(6):4349-4359. doi: 10.1016/j.clnu.2021.01.011. Epub 2021 Jan 18.


Background & aims: Eating at night has been linked to impaired glucose metabolism and dyslipidaemia that is likely a consequence of an underlying disrupted circadian rhythm in metabolic processes. The aim of this study was to explore the gene expression differences after eating a standard test meal or high protein test meal at night compared with the same meal in the morning.

Methods: In a cross over design, 10 healthy adults fasted for >10 h and then completed four acute meal challenges at 8am and 8pm on non-consecutive days separated by a wash out, consuming either a high protein low carbohydrate test meal or an isocaloric standard protein and carbohydrate test meal. Fasting and two-hour postprandial blood samples were collected to measure gene expression. For a subset of five participants RNA sequencing was completed on the Illumina NextSeq500.

Results: The time of day a meal is consumed had an effect on which genes were differentially regulated in the acute postprandial period, with only 6.5% of differentially expressed genes the same both morning and night. More genes were involved in lipid metabolic pathways in the morning and immune pathways at night. RTqPCR analysis of target genes suggested that key regulatory genes responsible for nutrient sensing and lipid and glucose metabolism are differentially expressed at night. These may play a role in improved blood glucose control in peripheral tissues that is observed after eating in the morning but to a lesser extent or not at all at night. Modulation of the macronutrient composition of a meal led to changes in expression of genes involved in the circadian clock and metabolism.

Conclusions: Investigating the differences in the transcriptomic response to food at night provides a greater understanding of the mechanisms underlying the changing metabolic phenotypes, characterised by circulating metabolic biomarkers, according to the time of day.

Keywords: Carbohydrate; Circadian; Gene expression; Meal timing; Metabolism; Night.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Circadian Rhythm*
  • Cross-Over Studies
  • Dietary Proteins / administration & dosage*
  • Female
  • Humans
  • Immunity
  • Leukocytes, Mononuclear / metabolism*
  • Lipid Metabolism
  • Male
  • Meals*
  • Metabolic Networks and Pathways
  • Middle Aged
  • Postprandial Period
  • Transcriptome*


  • Blood Glucose
  • Dietary Proteins