Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans
Open accessAbstract
The circadian system regulates daily rhythms in lipid metabolism and adipose tissue function. Although disruption of circadian clock function is associated with negative cardiometabolic end points, very little is known about interindividual variation in circadian-regulated metabolic pathways. Here, we used targeted lipidomics-based approaches to profile the time course of 263 lipids in blood plasma in 20 healthy individuals. Over a span of 28 h, blood was collected every 4 h and plasma lipids were analyzed by HPLC/MS. Across subjects, about 13% of lipid metabolites showed circadian variation. Rhythmicity spanned all metabolite classes examined, suggesting widespread circadian control of lipid-mediated energy storage, transport, and signaling. Intersubject agreement for lipids identified as rhythmic was only about 20%, however, and the timing of lipid rhythms ranged up to 12 h apart between individuals. Healthy subjects therefore showed substantial variation in the timing and strength of rhythms across different lipid species. Strong interindividual differences were also observed for rhythms of blood glucose and insulin, but not cortisol. Using consensus clustering with iterative feature selection, subjects clustered into different groups based on strength of rhythmicity for a subset of triglycerides and phosphatidylcholines, suggesting that there are different circadian metabolic phenotypes in the general population. These results have potential implications for lipid metabolism disorders linked to circadian clock disruption.
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Lipidomics analysis has identified a set of lipids that oscillate across biological subtypes defined by lipid composition.
“Lipidomics analysis has elucidated a set of lipids that oscillate across biological subtypes defined by stratification by lipid composition (11).”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [11]
Eight species overlapped between this study and rhythmic metabolites, including LPC 16:0; triacylglycerols 52:2, 52:3, 54:3, 54:4, and 54:5; and diacylglycerols 36:2 and 36:3.
“we found eight overlapping species of significance, including LPC 16:0; triacylglycerols (TGs) (52:2, 52:3, TG 54:3, 54:4, 54:5), and diacylglycerols (DGs) (36:2, 36:3).”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [11]
DG 36:3 is regulated in a circadian fashion in humans and may indicate both circadian time and sleep debt.
“This metabolite is also regulated in a circadian fashion in humans (11), and as such may be an indicator of both circadian time and sleep debt.”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [11]
Under constant routine conditions in which exogenous factors are removed or fixed, only 10-20% of metabolites appear rhythmic.
“However, under constant routine conditions in which exogenous factors are removed or fixed, only 10–20% of metabolites appear rhythmic (5–7).”
From Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism (2018) · cites this paper as [7]
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- Authors
- Chua, E. C.-P., Shui, G., Lee, I. T.-G., Lau, P., Tan, L.-C., Yeo, S.-C., Lam, B. D., Bulchand, S., Summers, S. A., Puvanendran, K., Rozen, S. G., Wenk, M. R., & Gooley, J. J.
- Affiliations
- National University of Singapore (SG)
- National Neuroscience Institute (SG)
- Program in Neuroscience and Behavioral Disorders, Duke–National University of Singapore Graduate Medical School, Singapore 169857;
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-08-14
- Volume
- 110
- Issue
- 35
- Pages
- 14468-14473
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3761633
- OpenAlex
- W2014163381
- Cited by
- 221
- References
- 39
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 16 · 2023: 22 · 2022: 18 · 2021: 22 · 2020: 28 · 2019: 20 · 2018: 19 · 2017: 18 · 2016: 17 · 2015: 14 · 2014: 9
- FWCI
- 7.20
- 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)
- National University of Singapore (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- circadian rhythm, plasma lipids, lipid metabolism, circadian clock, interindividual variability, triglycerides, phosphatidylcholine, blood glucose, insulin, cortisol, circadian clock disruption, lipidomics
- MeSH terms
- Adult, Blood Glucose, Chromatography, High Pressure Liquid, Circadian Rhythm, Humans, Insulin, Lipids, Male, Phenotype, Mass Spectrometry, Young Adult
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