Abnormal hyperphosphatemic response to fasting in X-linked hypophosphatemic mice

Area of Science:

• Nephrology
• Endocrinology
• Mineral Metabolism

Background:

• Dietary phosphate intake significantly influences phosphate homeostasis.
• Renal phosphate transport adaptation is crucial for maintaining mineral balance.
• Fasting can alter plasma phosphate levels, but the underlying mechanisms require further investigation.

Purpose of the Study:

• To investigate whether renal inorganic phosphate (Pi) transport adaptation is a prerequisite for the hyperphosphatemic effect of fasting in animals previously fed a low Pi diet (LPD).
• To utilize X-linked hypophosphatemic (HYP) mice, which have impaired renal Pi transport adaptation, as a model to test this hypothesis.

Main Methods:

• HYP and control mice were fed either a high Pi diet (HPD) or LPD for 9 days.
• The influence of a subsequent 24-hour fast on plasma and urine Pi concentrations was assessed.
• Urinary Pi excretion was measured to estimate Pi mobilization from body stores.

Main Results:

• In control mice fed LPD, fasting markedly increased plasma Pi. In contrast, HYP mice fed LPD showed a decrease in plasma Pi during fasting.
• Fasting decreased plasma Pi in both control and HYP mice fed HPD.
• Pi mobilization from body stores during fasting was comparable between HYP and control mice across both diets.

Conclusions:

• Renal Pi transport adaptation to dietary Pi restriction is essential for the hyperphosphatemic response to fasting.
• HYP mice demonstrate that impaired renal adaptation prevents fasting-induced hyperphosphatemia.
• Pi mobilization from body stores during fasting appears normal in HYP mice, irrespective of prior Pi restriction.