Publication: Bignon Y, Wigger L, Ansermet C, Weger BD, Lagarrigue S, Centeno G, Durussel F, Götz L, Ibberson M, Pradervand S, Quadroni M, Weger M, Amati F, Gachon F, Firsov D. Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock. J Clin Invest. 2023 Mar 2:e167133. doi: 10.1172/JCI167133. Epub ahead of print. PMID: 36862511. 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 inducible deletion of the circadian clock regulator Bmal1 in the renal tubule (cKOt). With this unique resource, we demonstrated that ~30% RNAs, ~20% proteins and ~20% metabolites are rhythmic in kidneys of control mice. Several key metabolic pathways including NAD+ biosynthesis, fatty acid transport, carnitine shuttle,and b-oxidation displayed impairments in kidneys of cKOt, resulting in a perturbed mitochondrial activity. Carnitine reabsorption from the primary urine was one of the most impacted processes with a ~50% reduction in plasma carnitine levels and a parallel systemic decrease in tissues carnitine content. This suggests that the circadian clock in the renal tubule controls both kidney and systemic physiology. This record contains two separate mass-spectrometry metabolomics data sets associated with this study: Metabolic profile of renal tubules, MS/MS data, Metabolon, Morrisville, NC (N=60) Metabolic profile of blood plasma, MS/MS data, Biocrates, Innsbruck, Austria (N=60) For each data set, original data as received from the platforms and processed data as used in the data analysis are provided. Preprocessing of kidney data included removal of metabolites with more than 80% missing data values, median normalization, imputation and glog2 transformation. Preprocessing of plasma data included filtering of metabolites with any missing data and log2 transformation. Details of data processing are available in the STAR*methods of the publication. Data sets in other repositories associated with the same study: Additional data sets (transcriptomics, proteomics) pertaining to the same study have been deposited in public repositories: Gene Expression Omnibus (NCBI GEO), GSE216252 PRIDE Archive (EMBL-EBI), PXD036803

This work was supported by the Swiss National Science Foundation research grant 310030-188499 (to D.F.).