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Lipid molecular timeline profiling reveals diurnal crosstalk between the liver and circulation.

Cell reports (2021-02-04)
Richard R Sprenger, Martin Hermansson, Ditte Neess, Lena Sokol Becciolini, Signe Bek Sørensen, Rolf Fagerberg, Josef Ecker, Gerhard Liebisch, Ole N Jensen, Dennis E Vance, Nils J Færgeman, Robin W Klemm, Christer S Ejsing
ABSTRACT

Diurnal regulation of whole-body lipid metabolism plays a vital role in metabolic health. Although changes in lipid levels across the diurnal cycle have been investigated, the system-wide molecular responses to both short-acting fasting-feeding transitions and longer-timescale circadian rhythms have not been explored in parallel. Here, we perform time-series multi-omics analyses of liver and plasma revealing that the majority of molecular oscillations are entrained by adaptations to fasting, food intake, and the postprandial state. By developing algorithms for lipid structure enrichment analysis and lipid molecular crosstalk between tissues, we find that the hepatic phosphatidylethanolamine (PE) methylation pathway is diurnally regulated, giving rise to two pools of oscillating phosphatidylcholine (PC) molecules in the circulation, which are coupled to secretion of either very low-density lipoprotein (VLDL) or high-density lipoprotein (HDL) particles. Our work demonstrates that lipid molecular timeline profiling across tissues is key to disentangling complex metabolic processes and provides a critical resource for the study of whole-body lipid metabolism.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium deoxycholate monohydrate, BioUltra, ≥99.0% (NT)
Supelco
Tris(2-carboxyethyl)phosphine hydrochloride solution, 0.5 M, pH 7.0(aqueous solution; pH was adjusted with ammonium hydroxide)
Supelco
Ammonium acetate, LiChropur, eluent additive for LC-MS