High-salt diets provoke phosphorus absorption from the small intestine in mice

Recent studies indicate that tenapanor, an inhibitor of sodium/proton exchanger-3 (NHE3), diminishes intestinal phosphorus (Pi) absorption. Given NHE3’s pivotal role in sodium (Na+) metabolism, there is a suspected functional link between Na+ and Pi metabolism. High-salt diets (HSD) have been demonstrated to disrupt calcium (Ca2+) metabolism. Since Ca2+ and Pi share analogous metabolic pathways, it is yet to be determined whether HSD also impacts Pi metabolism. Male C57 mice were randomly assigned to three groups: a standard diet group, HSD groups for 1 week (HSD-1w) and 4 weeks (HSD-4w). Throughout the study, dietary intake and water consumption were monitored using metabolic cages, and urine and feces were collected. Blood pressure was measured using a noninvasive tail vein sphygmomanometer. Upon completion of the intervention, mice were euthanized under anesthesia for blood collection, and intestinal and renal tissues were harvested for molecular analysis. Although plasma Pi levels were comparable between HSD groups and the control group, HSD groups exhibited increased urinary Pi excretion and decreased fecal Pi excretion. The HSD-4w group displayed elevated parathyroid hormone levels, reduced fibroblast growth factor 23 levels, and higher renal Cyp27b1 mRNA expression. The expression of sodium-dependent phosphate transporter 2b (Npt2b) and NHE3 was elevated in the intestine of HSD mice. HSD disrupts Pi metabolism by enhancing urinary Pi excretion and altering hormonal levels. The decrease in fecal Pi excretion, coupled with the upregulation of intestinal Pi transporter expression, suggests that HSD promotes intestinal Pi absorption in mice.

近期研究表明，替拉帕诺（tenapanor）作为钠氢交换体3（sodium/proton exchanger-3, NHE3）的抑制剂，可降低肠道对无机磷（phosphorus, Pi）的吸收。鉴于NHE3在钠（Na+）代谢中发挥关键作用，推测钠与磷代谢之间存在功能性关联。高盐饮食（high-salt diets, HSD）已被证实会干扰钙（Ca2+）代谢；由于钙与磷的代谢途径相似，目前尚未明确高盐饮食是否也会影响磷代谢。将雄性C57小鼠随机分为三组：标准饮食组、高盐饮食1周组（HSD-1w）与高盐饮食4周组（HSD-4w）。实验全程通过代谢笼监测小鼠的饮食摄入量与饮水量，并收集尿液与粪便。采用无创尾静脉血压计测量小鼠血压。干预结束后，对小鼠实施麻醉下的安乐死并采集血液，同时摘取肠道与肾脏组织用于分子生物学分析。尽管高盐饮食组与对照组的血浆无机磷水平无显著差异，但高盐饮食组小鼠的尿磷排泄量升高、粪磷排泄量降低。HSD-4w组小鼠的甲状旁腺激素水平升高，成纤维细胞生长因子23（fibroblast growth factor 23, FGF23）水平降低，肾脏Cyp27b1 mRNA的表达水平更高。高盐饮食小鼠的肠道内，钠依赖性磷酸盐转运蛋白2b（sodium-dependent phosphate transporter 2b, Npt2b）与NHE3的表达均上调。高盐饮食通过增加尿磷排泄、改变激素水平干扰磷代谢。粪磷排泄减少伴随肠道磷转运蛋白表达上调，表明高盐饮食可促进小鼠肠道对无机磷的吸收。