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High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation

Item Type:Article
Title:High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation
Creators Name:Kitada, K. and Daub, S. and Zhang, Y. and Klein, J. D. and Nakano, D. and Pedchenko, T. and Lantier, L. and LaRocque, L.M. and Marton, A. and Neubert, P. and Schroeder, A. and Rakova, N. and Jantsch, J. and Dikalova, A.E. and Dikalov, S.I. and Harrison, D.G. and Mueller, D.N. and Nishiyama, A. and Rauh, M. and Harris, R. C. and Luft, F.C. and Wassermann, D.H. and Sands, J.M. and Titze, J.
Abstract: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.
Keywords:Dietary Sodium Chloride, Energy Metabolism, Kidney, Liver, Skeletal Muscle, Sodium, Urea, Water-Electrolyte Balance, Animals, Mice
Source:Journal of Clinical Investigation
ISSN:0021-9738
Publisher:American Society for Clinical Investigation (U.S.A.)
Volume:127
Number:5
Page Range:1944-1959
Date:1 May 2017
Official Publication:https://doi.org/10.1172/JCI88532
PubMed:View item in PubMed

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