SRP403809 PRJNA892713 GSE216252 Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock 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. Overall design: RNA was extracted from the renal tubules of 60 mice. Of these, 30 were conditional knockouts of Arntl (Bmal1) and 30 were of control genotype. They were housed under 12-hours light/12-hours dark cycles and were sacrificed at six different time points: zeitgeber time ZT 0, ZT 4, ZT 8, ZT 12, ZT 16, ZT 20 (ZT 0 being the time of light on and ZT 12 the time of light off). Five replicates per genotype and time point were included. Technical note: The FASTQ file for sample 56 ("Renal tubule, cKO genotype, ZT12, rep 5") is incomplete: The last 8201575 of 27714258 reads are missing. The original file was corrupted (truncated) at the sequencing facility due to a technical problem on a server cluster. However, the processed data file of this sample is unaffected and contains the raw read counts from the original, complete FASTQ data. GSE216252 pubmed 36862511