Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome
Open accessAbstract
Proteomics holds great promise for understanding human physiology, developing health biomarkers, and precision medicine. However, how much the plasma proteome varies with time of day and is regulated by the master circadian suprachiasmatic nucleus brain clock, assessed here by the melatonin rhythm, is largely unknown. Here, we assessed 24-h time-of-day patterns of human plasma proteins in six healthy men during daytime food intake and nighttime sleep in phase with the endogenous circadian clock (i.e., circadian alignment) versus daytime sleep and nighttime food intake out of phase with the endogenous circadian clock (i.e., circadian misalignment induced by simulated nightshift work). We identified 24-h time-of-day patterns in 573 of 1,129 proteins analyzed, with 30 proteins showing strong regulation by the circadian cycle. Relative to circadian alignment, the average abundance and/or 24-h time-of-day patterns of 127 proteins were altered during circadian misalignment. Altered proteins were associated with biological pathways involved in immune function, metabolism, and cancer. Of the 30 circadian-regulated proteins, the majority peaked between 1400 hours and 2100 hours, and these 30 proteins were associated with basic pathways involved in extracellular matrix organization, tyrosine kinase signaling, and signaling by receptor tyrosine-protein kinase erbB-2. Furthermore, circadian misalignment altered multiple proteins known to regulate glucose homeostasis and/or energy metabolism, with implications for altered metabolic physiology. Our findings demonstrate the circadian clock, the behavioral wake-sleep/food intake-fasting cycle, and interactions between these processes regulate 24-h time-of-day patterns of human plasma proteins and help identify mechanisms of circadian misalignment that may contribute to metabolic dysregulation.
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Changes in homeostasis or circadian biology are accompanied by rapid and acute metabolic changes.
“When changes occur in homeostasis or circadian biology, rapid and acute metabolic changes also happen (Depner et al., 2018).”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Depner et al., 2018
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Self-citationTiming of food intake: identifying contributing factors to design effective interventions
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- Authors
- Depner, C. M., Melanson, E. L., McHill, A. W., & Wright, K. P.
- Affiliations
- University of Colorado Boulder (US)
- VA Eastern Colorado Health Care System (US)
- Brigham and Women's Hospital (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2018-05-21
- Volume
- 115
- Issue
- 23
- Pages
- E5390-E5399
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6003375
- OpenAlex
- W2803363391
- Cited by
- 122
- References
- 76
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 15 · 2023: 16 · 2022: 14 · 2021: 20 · 2020: 14 · 2019: 13 · 2018: 4
- FWCI
- 7.18
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK092624, DK111161)
- HHS | NIH | National Heart, Lung, and Blood Institute (HL132150)
- Sleep Research Society Foundation (011-JP-16)
- SomaLogic, Inc (None)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- circadian clock, circadian misalignment, plasma proteome, sleep timing, meal timing, night shift work, melatonin, circadian alignment, glucose homeostasis, energy metabolism, extracellular matrix organization, tyrosine kinase signaling, ErbB2 signaling, immune function, metabolic dysfunction
- MeSH terms
- Adult, Circadian Rhythm, Eating, Humans, Male, Melatonin, Plasma, Sleep, Wakefulness, Work Schedule Tolerance, Proteome, Circadian Clocks, Healthy Volunteers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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