Effects Of Dietary Phosphate Research Articles

Effects of dietary phosphate on glucose and lipid metabolism.

Recent epidemiological and animal studies have suggested that excess intake of phosphate (Pi) is a risk factor for the progression of chronic kidney disease and its cardiovascular complications. However, little is known about the impact of dietary high Pi intake on the development of metabolic disorders such as obesity and type 2 diabetes. In this study, we investigated the effects of dietary Pi on glucose and lipid metabolism in healthy rats. Male 8-wk-old Sprague-Dawley rats were divided into three groups and given experimental diets containing varying amounts of Pi, i.e., 0.2 [low Pi(LP)], 0.6 [control Pi(CP)], and 1.2% [high Pi(HP)]. After 4 wk, the HP group showed lower visceral fat accumulation compared with other groups, accompanied by a low respiratory exchange ratio (V̇CO2/V̇O2) without alteration of locomotive activity. The HP group had lower levels of plasma insulin and nonesterified fatty acids. In addition, the HP group also showed suppressed expression of hepatic lipogenic genes, including sterol regulatory element-binding protein-1c, fatty acid synthase, and acetyl-CoA carboxylase, whereas there was no difference in hepatic fat oxidation among the groups. On the other hand, uncoupling protein (UCP) 1 and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression were significantly increased in the brown adipose tissue (BAT) of the HP group. Our data demonstrated that a high-Pi diet can negatively regulate lipid synthesis in the liver and increase mRNA expression related to lipid oxidation and UCP1 in BAT, thereby preventing visceral fat accumulation. Thus, dietary Pi is a novel metabolic regulator.

Effects of Dietary Phosphate on Adynamic Bone Disease in Rats with Chronic Kidney Disease – Role of Sclerostin?

High phosphate intake is known to aggravate renal osteodystrophy along various pathogenetic pathways. Recent studies have raised the possibility that dysregulation of the osteocyte Wnt/β-catenin signaling pathway is also involved in chronic kidney disease (CKD)-related bone disease. We investigated the role of dietary phosphate and its possible interaction with this pathway in an experimental model of adynamic bone disease (ABD) in association with CKD and hypoparathyroidism. Partial nephrectomy (Nx) and total parathyroidectomy (PTx) were performed in male Wistar rats. Control rats with normal kidney and parathyroid function underwent sham operations. Rats were divided into three groups and underwent pair-feeding for 8 weeks with diets containing either 0.6% or 1.2% phosphate: sham 0.6%, Nx+PTx 0.6%, and Nx+PTx 1.2%. In the two Nx+PTx groups, serum creatinine increased and blood ionized calcium decreased compared with sham control group. They also presented hyperphosphatemia and reduced serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels. Fractional urinary excretion of phosphate increased in Nx+PTx 1.2% rats despite lower PTH and FGF23 levels than in sham group. These biochemical changes were accompanied by a decrease in bone formation rates. The Nx+PTx 1.2% group had lower bone volume (BV/TV), higher osteoblast and osteocyte apoptosis, and higher SOST and Dickkopf-1 gene expression than the Nx+PTx 0.6% group. Nx+PTx 0.6% rat had very low serum sclerostin levels, and Nx+PTx 1.2% had intermediate sclerostin levels compared with sham group. Finally, there was a negative correlation between BV/TV and serum sclerostin. These results suggest that high dietary phosphate intake decreases bone volume in an experimental model of CKD-ABD, possibly via changes in SOST expression through a PTH-independent mechanism. These findings could have relevance for the clinical setting of CKD-ABD in patients who low turnover bone disease might be attenuated by optimal control of phosphate intake and/or absorption.

P4.20 Effects of dietary phosphate on extensive ectopic calcification in mdx mouse and its muscle function

P4.20 Effects of dietary phosphate on extensive ectopic calcification in mdx mouse and its muscle function

Effects of dietary phosphate and calcium intake on fibroblast growth factor-23.

Little is known about the influence of dietary phosphate intake on fibroblast growth factor-23 (FGF23) and its subsequent effects on vitamin D levels. This study addresses changes in intact FGF23 (iFGF23) and C-terminal FGF23 (cFGF23), phosphaturia, and levels of vitamin D on high and low phosphate and calcium intake. Ten healthy subjects adhered to a diet low or high in phosphate and calcium content for 36 hours each with a 1-week interval during which subjects adhered to their usual diet. Serum phosphate, calcium, vitamin D metabolites, parathyroid hormone (PTH), and FGF23 levels (cFGF23 and iFGF23) were measured several times a day. Phosphate, calcium, and creatinine excretion was measured in 24-hour urine on all study days. Serum phosphate levels and urinary phosphate increased during high dietary phosphate intake (from 1.11 to 1.32 mmol/L, P<0.0001 and 21.6 to 28.8 mmol/d, P=0.0005, respectively). FGF23 serum levels increased during high dietary phosphate/calcium intake (cFGF23 from 60 to 72 RU/ml, P<0.001; iFGF23 from 33 to 37 ng/L, P=0.003), whereas PTH declined. 1,25-dihydroxyvitamin D (1,25D) showed an inverse relation with FGF23. Variation in dietary phosphate and calcium intake induces changes in FGF23 (on top of a circadian rhythm) and 1,25D blood levels as well as in urinary phosphate excretion. These changes are detectable the day after the change in the phosphate content of meals. Higher FGF23 levels are associated with phosphaturia and a decline in 1,25D levels.

Effect of dietary phosphate on Na+-dependent phosphate cotransporters function and expression in the rat kidney

Three types (typeI, II, andIII) of sodium-dependent phosphate cotransporters have recently been isolated and shown to be expressed in the mammalian kidney. Understanding of the functional roles and regulation of each transporter is still fragmented, however. We analyzed the functional roles of each transporter by using antisense oligonucleotides in theXenopus oocytes expression system, and by localization in the proximal tubules of rat kidney using immunohistochemistry. Phosphate uptake in brush border membranes was increased by about 2 times in rats fed a low-phosphate, as compared with a high-phosphate, diet. Expression of typeI, II, andIII transporter mRNAs was observed in renal poly(A)+RNA, isolated from the rats fed a low-phosphate diet. Phosphate uptake increased about 2.5-fold inXenopus oocytes injected with the poly(A)+RNA, compared with those given RNA from rats fed a high-phosphate diet. Hybrid depletion of the typeII sodium-dependent phosphate transporter (NaPi-2), but not of the typeI (rNaPi-1) or typeIII transporters (PiT-1 and PiT-2), significantly decreased phosphate transport activity in oocytes injected with the poly(A)+RNA from each experimental group rat kidney. In rats fed the lowphosphate diet, NaPi-2 immunoreactivity increased markedly in the brush border membranes of renal proximal tubular cells, whereas rNaPi-1 protein was not changed. This study suggests that the typeII transporter functions mainly as a sodium-dependent phosphate cotransporter, and is regulated by dietary phosphate in the rat kidney.

Effect of dietary phosphate on transport properties of pig renal microvillus vesicles.

Dietary phosphate manipulation results in stable adaptive changes in the transport functions of microvillus membrane vesicles isolated from pig renal cortex. When assayed under sodium gradient conditions, phosphate uptake is enhanced 200--400% in vesicles prepared from animals maintained on a low-phosphate diet (0.22%) compared to high-phosphate diet controls (0.82%). When transport is assayed in sodium preequilibrated vesicles, a 100% enhancement of phosphate uptake is demonstrable. Stimulation of phosphate uptake into low-phosphate diet vesicles after the imposition of a sodium chloride gradient is equivalent if uptake is measured at pH 6.0 or 8.0 and can be kinetically characterized as resulting from a Vmax alteration in the phosphate transport system. Microvillus membrane vesicle phosphate transport is maximally stimulated after only 2 days of dietary deprivation. Although a longer period (1 and 2 wk) of phosphate restriction does not further stimulate phosphate transport, it does result in an inhibtion of other sodium gradient-dependent transport systems (glucose, alanine).

Interactions of Ca, P, Zn and alkaline phosphatase in the chick—III. Effects of dietary phosphate, NaCl and theophylline

1. 1. Low inorganic phosphate (P i) diets, fed to chicks for 3 days, caused severe hypophosphataemia, while elevating plasma Ca and Zn levels. 2. 2. (P i)-depletion also reduced duodenal mucosal (P i), mucosal nuclear (P i), mucosal alkaline phosphatase activity and increased the mucosal and nuclear Ca and Zn. 3. 3. Excess dietary NaCl enhanced bone mineralization, when dietary P was adequate, and tended to counteract the effects of (P i)-deprivation. 4. 4. Theophylline reduced the growth, feed efficiency, plasma and mucosal nuclear (P i), and tended to increase mucosal Ca and phosphatase. 5. 5. Mucosal phosphatase was positively correlated with plasma, mucosa and mucosal nuclear (P i) levels and was inversely related to mucosa Zn levels. 6. 6. Duodenal alkaline phosphatase may regulate the metabolism of Ca and Zn via effects on the movements of (P i).