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Kidney Week

Abstract: FR-PO595

Kidney-Specific and Sex-Dependent Action of the Circadian Clock Protein BMAL1 in the Renal Response to Dietary Potassium Deprivation

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic

Authors

  • Crislip, Gene Ryan, University of Florida, Gainesville, Florida, United States
  • Douma, Lauren G., University of Florida, Gainesville, Florida, United States
  • Masten, Sarah H., University of Florida, Gainesville, Florida, United States
  • Wingo, Charles S., University of Florida, Gainesville, Florida, United States
  • Gumz, Michelle L., University of Florida, Gainesville, Florida, United States
Background

BMAL1 is a core mammalian circadian clock transcription factor responsible for the tissue-specific regulation of thousands of genes. Male, but not female, kidney-specific BMAL1 knockout (KO) mice exhibit lower blood pressure compared to control mice (CNTL). The goal of this study was to determine the BMAL1-dependent response to five days of dietary potassium (K) deprivation in males and females.

Methods

We generated the KO using floxed exon 8 BMAL1 mice crossed with kidney-specific cadherin Cre+ mice. Floxed Cre- littermates were used as CNTL. Metabolic cages were used for 12 hr urine collections.

Results

There was not a genotype difference in food intake in either sex, however, males displayed a transient decrease throughout the treatment (M: P<0.05) but females had no change (F: P=0.4). Similarly, neither sex had a genotype difference in body weight. Body weight of males did not change from treatment (M: P=0.8) but females increased in weight (F: P<0.0001). K excretion throughout treatment was comparable between CNTL and KO in both sexes. The K excretion rate in males decreased within 24 hours of the start of treatment from baseline and remained low for the full 5 days (CNTL: 0.65±0.05 to 0.012±0.002; KO: 0.64±0.02 to 0.015±0.004 mmol; P<0.0001). Females exhibited a similar response in K excretion rates (CNTL: 0.38±0.09 to 0.03±0.009; KO: 0.42±0.08 to 0.003±0.01 mmol; P<0.0001). After an initial decrease in sodium (Na) excretion in males, rates remained lower than baseline throughout treatment in CNTL whereas KO increased back to baseline levels by day 5 of treatment (CNTL: .29±0.02 to 0.19±0.01; KO: 0.29±0.01 to 0.26±0.01 mmol; P<0.0001). Genotype-dependent differences in Na excretion were not apparent in females, however, there was a transient increase following treatment in CNTL and KO reaching its peak at day 4 (CNTL: 0.21±0.06 to 0.26±0.05; KO: 0.21±0.03 to 0.24±0.03 mmol; P<0.05). Male CNTL had greater cumulative Na compared with male KO (P<0.001) and both female groups.

Conclusion

Male kidney-specific BMAL1 KO mice exhibited a decrease in renal Na retention in response to a low K diet. Thus, BMAL1 functions in the sex-dependent response of the kidney to dietary K restriction.

Funding

  • NIDDK Support