Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_D6C488B3AAAF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock.
Journal
The Journal of clinical investigation
Author(s)
Bignon Y., Wigger L., Ansermet C., Weger B.D., Lagarrigue S., Centeno G., Durussel F., Götz L., Ibberson M., Pradervand S., Quadroni M., Weger M., Amati F., Gachon F., Firsov D.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Publication state
Published
Issued date
17/04/2023
Peer-reviewed
Oui
Volume
133
Number
8
Pages
e167133
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Circadian rhythmicity in renal function suggests rhythmic adaptations in renal metabolism. To decipher the role of the circadian clock in renal metabolism, we studied diurnal changes in renal metabolic pathways using integrated transcriptomic, proteomic, and metabolomic analysis performed on control mice and mice with an inducible deletion of the circadian clock regulator Bmal1 in the renal tubule (cKOt). With this unique resource, we demonstrated that approximately 30% of RNAs, approximately 20% of proteins, and approximately 20% of metabolites are rhythmic in the kidneys of control mice. Several key metabolic pathways, including NAD+ biosynthesis, fatty acid transport, carnitine shuttle, and β-oxidation, displayed impairments in kidneys of cKOt mice, resulting in perturbed mitochondrial activity. Carnitine reabsorption from primary urine was one of the most affected processes with an approximately 50% reduction in plasma carnitine levels and a parallel systemic decrease in tissue carnitine content. This suggests that the circadian clock in the renal tubule controls both kidney and systemic physiology.
Keywords
Mice, Animals, Circadian Clocks/genetics, Multiomics, Proteomics, Circadian Rhythm/physiology, Kidney/metabolism, Carnitine, ARNTL Transcription Factors/genetics, ARNTL Transcription Factors/metabolism, Bioenergetics, Bioinformatics, Fatty acid oxidation, Nephrology
Pubmed
Web of science
Open Access
Yes
Create date
05/03/2023 23:02
Last modification date
15/06/2023 6:56
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