High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation
High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation
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DOI：
10.1172/jci88532
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发表时间：
2017-05-01
影响因子：
15.9
通讯作者：
Titze, Jens
中科院分区：
文献类型：
--
作者：
Kitada, Kento;Daub, Steffen;Titze, Jens
钠尿调节细胞外液容量稳态包括抑制肾素-血管紧张素-醛固酮系统、压力性尿钠排泄和肾神经活动减少，这些作用伴随增加尿Na+排泄并导致尿量增加。由此产生的利钠素驱动的利尿水损失被认为是控制细胞外容量。在这里，我们已经证明，尿液浓度，因此调节水的保护，是一个重要的控制系统，尿液形成和细胞外容量的稳态在小鼠和人类在不同水平的盐摄入量。我们观察到肾脏浓缩机制将钠尿排泄与相应的肾脏水重吸收偶联，限制钠尿渗透性利尿，并导致同时的细胞外容量保护和盐排泄到尿液中的浓缩。这种饮食盐排泄的节水机制依赖于尿素转运蛋白驱动的肾脏尿素再循环以及肝脏和骨骼肌的尿素生产。肝脏和肝外尿素渗压产物用于肾水保护的能量密集性质需要重新优先考虑肝脏和骨骼肌中的能量和底物代谢，导致肝生酮和糖皮质激素驱动的肌肉catalysts，这可以通过增加食物摄入来预防。这种排钠-排尿、节水的原理依赖于代谢驱动的细胞外容量控制，并受肝脏、肌肉和肾脏协同作用的调节。
Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter-driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions.