| Title: |
Circadian and wake-dependent changes in human plasma polar metabolites during prolonged wakefulness: A preliminary analysis |
| Authors: |
Grant, LK; Ftouni, S; Nijagal, B; De Souza, DP; Tull, D; McConville, MJ; Rajaratnam, SMW; Lockley, SW; Anderson, C |
| Publisher Information: |
NATURE PORTFOLIO |
| Publication Year: |
2019 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
Establishing circadian and wake-dependent changes in the human metabolome are critical for understanding and treating human diseases due to circadian misalignment or extended wake. Here, we assessed endogenous circadian rhythms and wake-dependent changes in plasma metabolites in 13 participants (4 females) studied during 40-hours of wakefulness. Four-hourly plasma samples were analyzed by hydrophilic interaction liquid chromatography (HILIC)-LC-MS for 1,740 metabolite signals. Group-averaged (relative to DLMO) and individual participant metabolite profiles were fitted with a combined cosinor and linear regression model. In group-level analyses, 22% of metabolites were rhythmic and 8% were linear, whereas in individual-level analyses, 14% of profiles were rhythmic and 4% were linear. We observed metabolites that were significant at the group-level but not significant in a single individual, and metabolites that were significant in approximately half of individuals but not group-significant. Of the group-rhythmic and group-linear metabolites, only 7% and 12% were also significantly rhythmic or linear, respectively, in ≥50% of participants. Owing to large inter-individual variation in rhythm timing and the magnitude and direction of linear change, acrophase and slope estimates also differed between group- and individual-level analyses. These preliminary findings have important implications for biomarker development and understanding of sleep and circadian regulation of metabolism. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2045-2322 |
| Relation: |
https://hdl.handle.net/11343/247238 |
| Availability: |
https://hdl.handle.net/11343/247238 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.204596AF |
| Database: |
BASE |