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Abstract: TH-PO621

Daily Oscillation of the Plasma Inorganic Phosphate Concentration: Impact of Nampt Deficient Mice

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1301 Health Maintenance, Nutrition, and Metabolism: Basic

Authors

  • Tatsumi, Sawako, The University of Shiga Prefecture, Hikone, Shiga, Japan
  • Kaneko, Ichiro, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
  • Segawa, Hiroko, University of Tokushima Graduate School, Tokushima, Japan
  • Miyamoto, Ken-ichi, Tokushima University, Tokushima City, Japan
Background

Circulating inorganic phosphate (Pi) exhibits a remarkable daily oscillation based on food intake. In humans and rodents, the daily oscillation in response to food intake may be coordinated to control the intestinal absorption, renal excretion, cellular shifts, and extracellular concentration of Pi. Hyperphosphatemia is linked to vascular calcification with chronic kidney disease (CKD) and is an independent risk factor for cardiovascular mortality in hemodialysis patients. Despite the circadian variations, it is the fasting morning serum Pi concentration that is linked to cardiovascular events and mortality in most epidemiologic studies. However, mechanisms regulating the resulting oscillation are unknown. Here we investigated the roles of the sodium Pi cotransporter SLC34 (Npt2) family and nicotinamide phosphoribosyltransferase (Nampt) in the daily oscillation of plasma Pi levels.

Methods

We used Npt2−/− mice, liver-specific Nampt−/− and Nampt+/− mice to reveal the mechanisms of daily oscillation of the plasma Pi concentration.

Results

The daily oscillation of the plasma Pi concentration is roughly linked to urinary Pi excretion. The expression of renal Npt2a and Npt2c, and intestinal Npt2b proteins also exhibit a dynamic daily oscillation. Analyses of Npt2a−/− and Npt2c −/− revealed the importance of renal Pi reabsorption and cellular Pi shifts in the daily oscillation. In Npt2a+/+ and Npt2a−/−, fasting significantly increases plasma Pi concentration and disappeared completely daily oscillation compared with the feeding group.
The administration of nicotinamide (vitamin B3) and a specific Nampt inhibitor (FK866) in the active and rest phases revealed that the Nampt/NAD system is involved in renal Pi excretion. Additionally, for cellular shifts, liver-specific Nampt deletion disturbed the daily oscillation of plasma Pi during the rest but not the active phase.
In systemic Nampt+/− mice, NAD levels were significantly reduced in the liver, kidney, and intestine, and the daily oscillation of the plasma Pi concentration was attenuated.

Conclusion

The findings of the present study suggest that the Nampt/NAD+ system, together with the kidney and soft tissues, plays an important role in generating the daily oscillation of plasma Pi levels. It may enhance our understanding of the changes in plasma Pi levels in CKD patients.