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Time-of-day defines the risk of thermally abused frying oil to renal injury by modulating the diurnal dynamics of oxylipins

ABSTRACT: Modulation of circadian rhythms results in impaired homeostasis and susceptibility to disease development. Thus, new perspectives on nutrition emphasize the circadian timing of food intake. Here, we find that fried oil disrupted the conversionof epoxides to diols in kidney, and led to aggravated renal injury. Interestingly, the circadian rhythm of epoxides and its diols in the kidney and plasma showed a significant light-dark manner. We demonstrated that time-imposed feeding of fried oil during the active period showed limited damage to renal function, conversely, renal function was impaired during the inactive period. Remarkably, time-imposed epoxy stearic acid (EpSA) from fried oil during the inactive period disrupted the rhythmicity of epoxide hydrolases and related metabolites, and fueled the progression of renal fibrosis and injury. The effect of EpSA on SMA and E-cadherin, renalfibrosis biomarkers, are lost in knockouts of Ephx1 and Ephx2, which encodes for epoxide hydrolase. Besides, the inhibition of epoxide hydrolases by dietary supplementation of linoleic acid rescues mice from the damages from time-imposed feeding of EpSA. Our findings unveil that the time-of-day dependence of epoxide hydrolases and circadian disruption at the inactive phase by EpSA from fried oil has adverse impacts on kidney function.

ORGANISM(S): Mus musculus

PROVIDER: GSE269508 | GEO | 2026/05/01

REPOSITORIES: GEO

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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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Time-of-day defines the risk of thermally abused frying oil to renal injury by modulating the diurnal dynamics of oxylipins

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