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Circadian Proteomics Landscape of Mouse Livers Organized by Time-restricted Feeding: Ubiquitylation

ABSTRACT: Meal timing is essential in synchronization of circadian rhythms in different organ systems through clock-dependent and -independent mechanisms. The liver is a critical metabolic organ whose circadian clock and transcriptome can be readily reset by meal timing. However, it remains largely unexplored how circadian rhythms in the liver are organized in time-restricted feeding that intervenes meal timing. Here, we applied affinity-purification based shotgun proteomics for ubiquitylation to characterize circadian features associated with day/sleep- (DRF) and night/wake (NRF)-time restricted feeding in nocturnal female mice. The transcriptomics and metabolomics datasets are public (see www.circametdb.org.cn).

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Min-Dian Li

LAB HEAD: Min-Dian Li

PROVIDER: PXD038481 | Pride | 2023-08-22

REPOSITORIES: Pride

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			Action	DRS
	HFX4_FPEP191631074-5A.raw	Raw
	HFX4_FPEP191631075-5A.raw	Raw
	HFX4_FPEP191631076-3A.raw	Raw
	HFX4_FPEP191631077-3A.raw	Raw
	HFX4_FPEP191631078-3A.raw	Raw

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Project description:Recent evidence suggest that the circadian timing system plays an important role in the control of renal function and maintaining blood pressure. Here, we analyzed circadian rhythms of urinary excretion of sodium and potassium in wild-type mice and mice lacking circadian transcriptional activator clock. Analysis of urines collected at hourly intervals over a 24-hour period revealed dramatic changes in rhythms of sodium and potassium excretion in clock(-/-) mice. In parallel, significant differences in circadian pattern of plasma aldosterone levels, but not in the 24-hour mean aldosterone levels, were observed. Microarray-based profiling of renal transcriptomes demonstrated that clock(-/-) mice exhibit dysregulation in multiple mechanisms involved in maintaining sodium and potassium balance by the kidney. The most significant changes were detected in the expression levels of several key enzymes (Cyp4a14, Cyp4a12a and Cyp4a12b) required for the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a powerful regulator of renal sodium and potassium excretion, renal vascular tone and blood pressure. The 20-HETE levels measured in kidney microsomes of wild-type mice followed a circadian-like temporal pattern. In clock(-/-) mice, the acrophase of this rhythm was shifted by 8 hours and the 24-hour mean levels of 20-HETE were significantly decreased. These results demonstrate that circadian rhythms of urine electrolyte excretion are largely dependent on the circadian clock activity and indicate that circadian oscillations in renal 20-HETE content could be an important mechanism of blood pressure regulation. We examined the temporal profiles of gene expression in mouse whole kidney. Animals were sacrificed for microdissection every 4 hours, i.e. at ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20 (ZT M-bM-^@M-^S Zeitgeber (circadian) time, indicates time of light-on as ZT0 and time of light-off as ZT12). The microarray hybridization was performed in duplicates on pools of RNA composed of equivalent amounts of RNA prepared from teo or three animals at each ZT time-point.

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Circadian Proteomics Landscape of Mouse Livers Organized by Time-restricted Feeding: Ubiquitylation

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