Format

Send to

Choose Destination
FASEB J. 2017 Dec;31(12):5557-5567. doi: 10.1096/fj.201700323R. Epub 2017 Aug 18.

Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes.

Author information

1
Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom.
2
Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom d.skene@surrey.ac.uk.

Abstract

Metabolic profiling of individuals with type 2 diabetes mellitus (T2DM) has previously been limited to single-time-point samples, ignoring time-of-day variation. Here, we tested our hypothesis that body mass and T2DM affect daily rhythmicity and concentrations of circulating metabolites across a 24-h day in 3 age-matched, male groups-lean, overweight/obese (OW/OB), and OW/OB with T2DM-in controlled laboratory conditions, which were not confounded by large meals. By using targeted liquid chromatography/mass spectrometry metabolomics, we quantified 130 plasma metabolites every 2 h over 24 h, and we show that average metabolite concentrations were significantly altered by increased body mass (90 of 130) and T2DM (56 of 130). Thirty-eight percent of metabolites exhibited daily rhythms in at least 1 study group, and where a metabolite was rhythmic in >1 group, its peak time was comparable. The optimal time of day was assessed to provide discriminating biomarkers. This differed between metabolite classes and study groups-for example, phospholipids showed maximal difference at 5:00 AM (lean vs. OW/OB) and at 5:00 PM (OW/OB vs. T2DM). Metabolites that were identified with both robust 24-h rhythms and significant concentration differences between study groups emphasize the importance of controlling the time of day for diagnosis and biomarker discovery, offering a significant improvement over current single sampling.-Isherwood, C. M., Van der Veen, D. R., Johnston, J. D., Skene, D. J. Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes.

KEYWORDS:

biological rhythms; circadian clock; human; metabolomics; obesity

PMID:
28821636
PMCID:
PMC5690388
DOI:
10.1096/fj.201700323R
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center