Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chua, EC-P; Shui, G; Lee, IT-G; Lau, P; Tan, L-C; Yeo, S-C; Lam, BD; Bulchand, S; Summers, SA; Puvanendran, K; Rozen, SG; Wenk, MR; Gooley, JJ

Published Date

  • August 27, 2013

Published In

Volume / Issue

  • 110 / 35

Start / End Page

  • 14468 - 14473

PubMed ID

  • 23946426

Pubmed Central ID

  • 23946426

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1222647110

Language

  • eng

Conference Location

  • United States