Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans.
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.
Program in Neuroscience and Behavioral Disorders, Duke-National University of Singapore Graduate Medical School, Singapore 169857.
Eric Chern-Pin
EC
Chua
Guanghou
G
Shui
Ivan Tian-Guang
IT
Lee
Pauline
P
Lau
Luuan-Chin
LC
Tan
Sing-Chen
SC
Yeo
Buu Duyen
BD
Lam
Sarada
S
Bulchand
Scott A
SA
Summers
Kathiravelu
K
Puvanendran
Steven G
SG
Rozen
Markus R
MR
Wenk
Joshua J
JJ
Gooley
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry; D010641:Phenotype; D055815:Young Adult
D001786:Blood Glucose; D007328:Insulin; D008055:Lipids
chronobiology; metabolomics