High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation
Kitada K, Daub S, Zhang Y, Klein JD, Nakano D, Pedchenko T, Lantier L, Larocque LM, Marton A, Neubert P, Schröder A, Rakova N, Jantsch J, Dikalova AE, Dikalov SI, Harrison DG, Mueller DN, Nishiyama A, Rauh M, Harris RC, Luft FC, Wassermann DH, Sands JM, Titze J (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 127
Pages Range: 1944-1959
Journal Issue: 5
DOI: 10.1172/JCI88532
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.
Authors with CRIS profile
Agnes Schröder
Interdisziplinäres Zentrum für Klinische Forschung IZKF-Förderlinien
Manfred Rauh
Department of Paediatrics and Adolescent Medicine
Involved external institutions
Vanderbilt University
United States (USA) (US)
Kagawa University
Japan (JP)
Charité - Universitätsmedizin Berlin
Germany (DE)
Emory University
United States (USA) (US)
Universitätsklinikum Regensburg
Germany (DE)
United States (USA) (US)
Kagawa University
Japan (JP)
Charité - Universitätsmedizin Berlin
Germany (DE)
Emory University
United States (USA) (US)
Universitätsklinikum Regensburg
Germany (DE)
How to cite
APA:
Kitada, K., Daub, S., Zhang, Y., Klein, J.D., Nakano, D., Pedchenko, T.,... Titze, J. (2017). High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation. Journal of Clinical Investigation, 127(5), 1944-1959. https://dx.doi.org/10.1172/JCI88532
MLA:
Kitada, Kento, et al. "High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation." Journal of Clinical Investigation 127.5 (2017): 1944-1959.
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