Abstract
NaPi-IIb/Slc34a2 is a Na+-dependent phosphate transporter that accounts for the majority of active phosphate transport into intestinal epithelial cells. Its abundance is regulated by dietary phosphate, being high during dietary phosphate restriction. Intestinal ablation of NaPi-IIb in mice leads to increased fecal excretion of phosphate, which is compensated by enhanced renal reabsorption. Here we compared the adaptation to dietary phosphate of wild type (WT) and NaPi-IIb−/− mice. High phosphate diet (HPD) increased fecal and urinary excretion of phosphate in both groups, though NaPi-IIb−/− mice still showed lower urinary excretion than WT. In both genotypes low dietary phosphate (LDP) resulted in reduced fecal excretion and almost undetectable urinary excretion of phosphate. Consistently, the expression of renal cotransporters after prolonged LDP was similar in both groups. Plasma phosphate declined more rapidly in NaPi-IIb−/− mice upon LDP, though both genotypes had comparable levels of 1,25(OH)2vitamin D3, parathyroid hormone and fibroblast growth factor 23. Instead, NaPi-IIb−/− mice fed LDP had exacerbated hypercalciuria, higher urinary excretion of corticosterone and deoxypyridinoline, lower bone mineral density and higher number of osteoclasts. These data suggest that during dietary phosphate restriction NaPi-IIb-mediated intestinal absorption prevents excessive demineralization of bone as an alternative source of phosphate.
Highlights
Phosphate (Pi) is vital for many biological functions including energy metabolism, intracellular signaling, structural composition of cellular membranes, and bone mineralization
The fecal excretion of Pi reflected the dietary Pi content: it was higher in animals fed high Pi and progressively lower in those fed low Pi as compared with mice kept on normal chow (Fig. 1A)
Except for the High phosphate diet (HPD), there was a tendency for increased fecal Pi excretion in NaPi-IIb−/− compared with wild type (WT) mice, which was only significant during normal dietary conditions when absolute values were compared
Summary
Phosphate (Pi) is vital for many biological functions including energy metabolism, intracellular signaling, structural composition of cellular membranes, and bone mineralization. WT and NaPi-IIb−/− mice fed a LPD for 3 days showed higher levels of plasma 1,25-(OH)[2] vitamin D3 compared to animals fed a HPD (Fig. 2A).
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