Supplemental Nicotinamide Dose-Dependently Regulates Body Phosphorus Excretion via Altering Type II Sodium-Phosphate Co-Transporter Expressions in Laying Hens

Abstract

Background Dietary supplemental nicotinamide is used to treat hyperphosphatemia in humans. However, the mechanisms of its impact on body phosphorus homeostasis remain unclear. Objective This study was to determine effects and molecular mechanisms of 3 dietary nicotinamide concentrations on body phosphorus homeostasis in laying hens. Methods Hy-Line Brown layers (total = 21; 40 wk old; body weight: 1,876 ± 24 g) were individually housed (n = 7) and fed a corn-soybean meal–based diet supplemented with nicotinamide at 20 (N20), 140 (N140), and 1000 (N1000) mg/kg for 21 d. Serum phosphorus and fibroblast growth factor 23 (FGF23) concentrations, phosphorus and calcium excretion, and mRNA and/or protein of type II sodium-phosphate co-transporters (NPt2a, NPt2ab) and FGF23 and FGF23 receptors were measured in the intestines, calvaria, kidney, and liver. Results Hens in the N1000 group had a 16% lower serum phosphorus concentration and 22% greater phosphorus excretion than those in the N20 or N140 group (P ≤ 0.05). Compared with hens in the N20 group, hens in the N140 and N1000 groups, which did not differ, had 15–21% lower serum FGF23 concentrations, 19–22% greater calcium excretion, 43–56% lower ileum NPT2b protein production, and 1.5- to 1.6-fold greater kidney NPT2a protein production, respectively (all differences at P ≤ 0.05). Conclusions Supplementing high concentrations of nicotinamide in diets for laying hens led to accelerated phosphorus and calcium excretions and decreased serum phosphorus and FGF23 concentrations, which were associated with downregulated intestinal NPt2b protein production. Our findings exclude kidney NPt2a protein production as a primary mechanism for the nicotinamide-induced body phosphorus loss.

Hyperphosphatemia and Cardiovascular Disease

“…Phosphate binders inhibited the absorption of phosphate, but also up-regulated the active phosphate transporter Npt-2b in the intestine (Isakova et al, 2015). Nicotinamide, the metabolite of vitamin B3, could reduce phosphate by inhibiting the intestinal phosphate transporter Npt-2b, which is a secondline drug for phosphate lowering treatment (Ren et al, 2020). It has been reported that nicotinamide can reduce phosphate by 12-34% in end-stage CKD dialysis patients (Vogt et al, 2019).…”

Dietary vitamin D3 deprivation suppresses fibroblast growth factor 23 signals by reducing serum phosphorus levels in laying hens

“…Our results showed that dietary vitamin D 3 deficiency reduces the mRNA expression of FGFR (including FGFR1 , FGFR2 , FGFR3 and FGFR4 ) and VDR in the calvaria, but has no effect on the liver. Hepatic FGF23 mRNA expression is not sensitive to dietary phosphorus, nicotinamide and vitamin D 3 levels ( Ren et al., 2020b , 2020c ), suggesting that FGF23 may be related to other physiological functions in laying hens. Calvaria FGFR1 can sense changes in extracellular phosphorus levels and regulate the production of FGF23 ( Takashi et al., 2019 ).…”

“…Briefly, eggshell thickness was measured using a dial pipe gauge (ETG-1061; Robotmation, Co., Ltd., Tokyo, Japan); eggshell strength was measured using a texture analyzer (EFG-0503; Robotmation, Co., Ltd., Tokyo, Japan); egg yolk color, albumen height, and Haugh units were tested using a multifunction egg quality analyzer (EMT-5200; Robotmation, Co., Ltd., Tokyo, Japan); specific gravity was measured using a flotation method in saline solutions; shell index was calculated as shell weight of whole egg; 2) 24-h total excreta from each laying hen was collected for the determination of phosphorus and calcium excretion; 3) calvaria, liver, intestinal mucosa (duodenum, jejunum and ileum) and kidney samples were collected after euthanasia, frozen in liquid nitrogen, and then transferred to a −80 °C freezer until further analysis. All experimental analysis methods were performed as previously described ( Liu et al., 2018 ; Ren et al., 2020b , 2020c ).…”

Low-calcium diets increase duodenal mRNA expression of calcium and phosphorus transporters and claudins but compromise growth performance irrespective of microbial phytase inclusion in broilers

“…Furthermore, dietary phytase inclusion enhanced serum P concentration ( Table 5 ), which might have stimulated FGF23 secretion from the bone ( Ren et al., 2017 ). A higher serum FGF23 circulation has been shown to be coupled with a greater NaPi-IIb protein expression in the duodenal mucosa of layers ( Ren et al., 2020 ). Taken together, expression of P transporters is consistent with intestinal P absorption in broilers.…”