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Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock
Yohan Bignon, … , Frédéric Gachon, Dmitri Firsov
Yohan Bignon, … , Frédéric Gachon, Dmitri Firsov
Published March 2, 2023
Citation Information: J Clin Invest. 2023;133(8):e167133. https://doi.org/10.1172/JCI167133.
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Research Article Nephrology Article has an altmetric score of 25

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

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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.

Authors

Yohan Bignon, Leonore Wigger, Camille Ansermet, Benjamin D. Weger, Sylviane Lagarrigue, Gabriel Centeno, Fanny Durussel, Lou Götz, Mark Ibberson, Sylvain Pradervand, Manfredo Quadroni, Meltem Weger, Francesca Amati, Frédéric Gachon, Dmitri Firsov

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Figure 1

Alterations of renal transcriptome and renal proteome in cKOt mice.

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Alterations of renal transcriptome and renal proteome in cKOt mice.
(A) ...
(A) Donut charts showing the percentage of rhythmic, nonrhythmic and unassigned renal transcripts in control (Ctrl) and cKOt mice. (B) Histogram showing the number and percentage of renal rhythmic transcripts assigned to dryR rhythmicity models. (C) Histogram showing the acrophase distribution of renal transcripts assigned to dryR rhythmicity models 2, 3, 4, and 5. Red dashed lines: kernel density estimates. (D) Cumulative number of renal transcripts assigned in the indicated rhythmicity pattern in function of amplitude. (E) Donut charts showing the proportion of renal transcripts displaying a differential mean expression according to limma R package (72) in Ctrl versus cKOt mice for each dryR rhythmicity model. (F) Donut charts showing the percentage of rhythmic, not rhythmic, and unassigned renal proteins in Ctrl and cKOt mice. (G) Histogram showing the number and percentage of renal rhythmic proteins assigned to dryR rhythmicity models. (H) Histogram showing the acrophase distribution of renal proteins assigned to dryR rhythmicity models 2, 3, 4, and 5. Red dashed lines: kernel density estimates. (I) Cumulative number of renal proteins assigned in the indicated rhythmicity pattern in function of amplitude. (J) Donut charts showing the proportion of renal proteins displaying a differential mean expression according to limma R package in control (Ctrl) versus cKOt mice for each dryR rhythmicity model.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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