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

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

doi:10.1016/j.celrep.2021.108710

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

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^*

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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.

Originalsprog	Engelsk
Artikelnummer	108710
Tidsskrift	Cell Reports
Vol/bind	34
Udgave nummer	5
Antal sider	23
ISSN	2211-1247
DOI	https://doi.org/10.1016/j.celrep.2021.108710
Status	Udgivet - 2. feb. 2021

Bibliografisk note

Funding Information:
We thank Alba Diz-Muñoz, Sabbi Lall, Nils Hoffmann, and Robert Ahrends for constructive comments and Peter Højrup for amino acid analysis. This research was supported by the VILLUM Foundation ( VKR023439 to C.S.E.), the VILLUM Center for Bioanalytical Sciences ( VKR023179 to O.N.J. and C.S.E.), and the Lundbeckfonden ( R44-A4342 and R54-A5858 to C.S.E.). The research leading to these results has received funding from the European Union Seventh Framework Programme ( FP7-2007-2013 ) under grant agreement “HEALTH-F2-2013-602222 (Athero-Flux)” (O.N.J. and C.S.E.).

Publisher Copyright:
© 2021 The Author(s)

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Dokumenter og links

10.1016/j.celrep.2021.108710Licens: CC BY

Open Access VersionForlagets udgivne version, 5,91 MBLicens: CC BY

Citationsformater

Sprenger, R. R., Hermansson, M., Neess, D., Becciolini, L. S., Sørensen, S. B., Fagerberg, R., Ecker, J., Liebisch, G., Jensen, O. N., Vance, D. E., Færgeman, N. J., Klemm, R. W., & Ejsing, C. S. (2021). Lipid molecular timeline profiling reveals diurnal crosstalk between the liver and circulation. Cell Reports, 34(5), Artikel 108710. https://doi.org/10.1016/j.celrep.2021.108710

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title = "Lipid molecular timeline profiling reveals diurnal crosstalk between the liver and circulation",

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.",

keywords = "blood plasma, circadian rhythm, diurnal regulation, fasting-feeding cycles, lipidomics, lipoprotein particles, liver, PE methylation pathway, Pemt, proteomics",

author = "Sprenger, {Richard R.} and Martin Hermansson and Ditte Neess and Becciolini, {Lena Sokol} and S{\o}rensen, {Signe Bek} and Rolf Fagerberg and Josef Ecker and Gerhard Liebisch and Jensen, {Ole N.} and Vance, {Dennis E.} and F{\ae}rgeman, {Nils J.} and Klemm, {Robin W.} and Ejsing, {Christer S.}",

note = "Funding Information: We thank Alba Diz-Mu{\~n}oz, Sabbi Lall, Nils Hoffmann, and Robert Ahrends for constructive comments and Peter H{\o}jrup for amino acid analysis. This research was supported by the VILLUM Foundation ( VKR023439 to C.S.E.), the VILLUM Center for Bioanalytical Sciences ( VKR023179 to O.N.J. and C.S.E.), and the Lundbeckfonden ( R44-A4342 and R54-A5858 to C.S.E.). The research leading to these results has received funding from the European Union Seventh Framework Programme ( FP7-2007-2013 ) under grant agreement “HEALTH-F2-2013-602222 (Athero-Flux)” (O.N.J. and C.S.E.). Publisher Copyright: {\textcopyright} 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.celrep.2021.108710",

language = "English",

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AU - Sprenger, Richard R.

AU - Hermansson, Martin

AU - Neess, Ditte

AU - Becciolini, Lena Sokol

AU - Sørensen, Signe Bek

AU - Fagerberg, Rolf

AU - Ecker, Josef

AU - Liebisch, Gerhard

AU - Jensen, Ole N.

AU - Vance, Dennis E.

AU - Færgeman, Nils J.

AU - Klemm, Robin W.

AU - Ejsing, Christer S.

N1 - Funding Information: We thank Alba Diz-Muñoz, Sabbi Lall, Nils Hoffmann, and Robert Ahrends for constructive comments and Peter Højrup for amino acid analysis. This research was supported by the VILLUM Foundation ( VKR023439 to C.S.E.), the VILLUM Center for Bioanalytical Sciences ( VKR023179 to O.N.J. and C.S.E.), and the Lundbeckfonden ( R44-A4342 and R54-A5858 to C.S.E.). The research leading to these results has received funding from the European Union Seventh Framework Programme ( FP7-2007-2013 ) under grant agreement “HEALTH-F2-2013-602222 (Athero-Flux)” (O.N.J. and C.S.E.). Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/2

Y1 - 2021/2/2

N2 - 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.

AB - 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.

KW - blood plasma

KW - circadian rhythm

KW - diurnal regulation

KW - fasting-feeding cycles

KW - lipidomics

KW - lipoprotein particles

KW - liver

KW - PE methylation pathway

KW - Pemt

KW - proteomics

U2 - 10.1016/j.celrep.2021.108710

DO - 10.1016/j.celrep.2021.108710

M3 - Journal article

C2 - 33535053

AN - SCOPUS:85100374541

SN - 2211-1247

VL - 34

JO - Cell Reports

JF - Cell Reports

IS - 5

M1 - 108710

ER -

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

Abstract

Bibliografisk note

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Fingeraftryk

Citationsformater