Multiomics Reveals Multilevel Control of Renal and Systemic Metabolism by the Renal Tubular Circadian Clock

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2023 Mar 2

PMID 36862511

Authors

Yohan Bignon

Leonore Wigger

Camille Ansermet

Benjamin D Weger

Sylviane Lagarrigue

Gabriel Centeno

Fanny Durussel

Lou Gotz

Mark Ibberson

Sylvain Pradervand

Manfredo Quadroni

Meltem Weger

Francesca Amati

Frederic Gachon

Dmitri Firsov

Affiliations

Soon will be listed here.

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.

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