Hyperaldosteronism in klotho-deficient mice

Stephanie S. Fischer, Daniela S. Kempe, Christina B. Leibrock, Rexhep Rexhepaj, Balasaheb Siraskar, Krishna M. Boini, Teresa F. Ackermann, Michael Föller, Berthold Hocher, Kevin P. Rosenblatt, Makoto Kuro-o, Florian Lang

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Klotho is a membrane protein participating in the inhibitory effect of FGF23 on the formation of 1,25-dihydroxyvitamin-D3 [1,25(OH) 2D3]. It participates in the regulation of renal tubular phosphate reabsorption and stimulates renal tubular Ca2+ reabsorption. Klotho hypomorphic mice (klothohm) suffer from severe growth deficit, rapid aging, and early death, events largely reversed by a vitamin D-deficient diet. The present study explored the role of Klotho deficiency in mineral and electrolyte metabolism. To this end, klotho hm mice and wild-type mice (klotho+/+) were subjected to a normal (D+) or vitamin D-deficient (D-) diet or to a vitamin D-deficient diet for 4 wk and then to a normal diet (D-/+). At the age of 8 wk, body weight was significantly lower in klotho hmD+ mice than in klotho+/+D+ mice, klothohmD- mice, and klothohmD-/+ mice. Plasma concentrations of 1,25(OH)2D3, adrenocorticotropic hormone (ACTH), antidiuretic hormone (ADH), and aldosterone were significantly higher in klothohmD+ mice than in klotho+/+D+ mice. Plasma volume was significantly smaller in klothohmD-/+ mice, and plasma urea, Ca2+, phosphate and Na+, but not K+ concentrations were significantly higher in klothohmD+ mice than in klotho+/+D+ mice. The differences were partially abrogated by a vitamin D-deficient diet. Moreover, the hyperaldosteronism was partially reversed by Ca2+-deficient diet. Ussing chamber experiments revealed a marked increase in amiloride-sensitive current across the colonic epithelium, pointing to enhanced epithelial sodium channel (ENaC) activity. A salt-deficient diet tended to decrease and a salt-rich diet significantly increased the life span of klothohmD+ mice. In conclusion, the present observation disclose that the excessive formation of 1,25(OH)2D 3 in Klotho-deficient mice results in extracellular volume depletion, which significantly contributes to the shortening of life span.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume299
Issue number5
DOIs
StatePublished - Nov 2010

Fingerprint

Hyperaldosteronism
Diet
Vitamin D
Salts
Phosphates
Epithelial Sodium Channels
Plasma Volume
Calcitriol
Amiloride
Aldosterone
Vasopressins
Adrenocorticotropic Hormone
Electrolytes
Minerals
Urea

Keywords

  • Calcitriol
  • Calcium
  • Cell volume
  • Phosphate
  • Sodium

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Fischer, S. S., Kempe, D. S., Leibrock, C. B., Rexhepaj, R., Siraskar, B., Boini, K. M., ... Lang, F. (2010). Hyperaldosteronism in klotho-deficient mice. American Journal of Physiology - Renal Physiology, 299(5). https://doi.org/10.1152/ajprenal.00233.2010

Hyperaldosteronism in klotho-deficient mice. / Fischer, Stephanie S.; Kempe, Daniela S.; Leibrock, Christina B.; Rexhepaj, Rexhep; Siraskar, Balasaheb; Boini, Krishna M.; Ackermann, Teresa F.; Föller, Michael; Hocher, Berthold; Rosenblatt, Kevin P.; Kuro-o, Makoto; Lang, Florian.

In: American Journal of Physiology - Renal Physiology, Vol. 299, No. 5, 11.2010.

Research output: Contribution to journalArticle

Fischer, SS, Kempe, DS, Leibrock, CB, Rexhepaj, R, Siraskar, B, Boini, KM, Ackermann, TF, Föller, M, Hocher, B, Rosenblatt, KP, Kuro-o, M & Lang, F 2010, 'Hyperaldosteronism in klotho-deficient mice', American Journal of Physiology - Renal Physiology, vol. 299, no. 5. https://doi.org/10.1152/ajprenal.00233.2010
Fischer SS, Kempe DS, Leibrock CB, Rexhepaj R, Siraskar B, Boini KM et al. Hyperaldosteronism in klotho-deficient mice. American Journal of Physiology - Renal Physiology. 2010 Nov;299(5). https://doi.org/10.1152/ajprenal.00233.2010
Fischer, Stephanie S. ; Kempe, Daniela S. ; Leibrock, Christina B. ; Rexhepaj, Rexhep ; Siraskar, Balasaheb ; Boini, Krishna M. ; Ackermann, Teresa F. ; Föller, Michael ; Hocher, Berthold ; Rosenblatt, Kevin P. ; Kuro-o, Makoto ; Lang, Florian. / Hyperaldosteronism in klotho-deficient mice. In: American Journal of Physiology - Renal Physiology. 2010 ; Vol. 299, No. 5.
@article{6d4d08b6072d469488f8af52f8a2b32a,
title = "Hyperaldosteronism in klotho-deficient mice",
abstract = "Klotho is a membrane protein participating in the inhibitory effect of FGF23 on the formation of 1,25-dihydroxyvitamin-D3 [1,25(OH) 2D3]. It participates in the regulation of renal tubular phosphate reabsorption and stimulates renal tubular Ca2+ reabsorption. Klotho hypomorphic mice (klothohm) suffer from severe growth deficit, rapid aging, and early death, events largely reversed by a vitamin D-deficient diet. The present study explored the role of Klotho deficiency in mineral and electrolyte metabolism. To this end, klotho hm mice and wild-type mice (klotho+/+) were subjected to a normal (D+) or vitamin D-deficient (D-) diet or to a vitamin D-deficient diet for 4 wk and then to a normal diet (D-/+). At the age of 8 wk, body weight was significantly lower in klotho hmD+ mice than in klotho+/+D+ mice, klothohmD- mice, and klothohmD-/+ mice. Plasma concentrations of 1,25(OH)2D3, adrenocorticotropic hormone (ACTH), antidiuretic hormone (ADH), and aldosterone were significantly higher in klothohmD+ mice than in klotho+/+D+ mice. Plasma volume was significantly smaller in klothohmD-/+ mice, and plasma urea, Ca2+, phosphate and Na+, but not K+ concentrations were significantly higher in klothohmD+ mice than in klotho+/+D+ mice. The differences were partially abrogated by a vitamin D-deficient diet. Moreover, the hyperaldosteronism was partially reversed by Ca2+-deficient diet. Ussing chamber experiments revealed a marked increase in amiloride-sensitive current across the colonic epithelium, pointing to enhanced epithelial sodium channel (ENaC) activity. A salt-deficient diet tended to decrease and a salt-rich diet significantly increased the life span of klothohmD+ mice. In conclusion, the present observation disclose that the excessive formation of 1,25(OH)2D 3 in Klotho-deficient mice results in extracellular volume depletion, which significantly contributes to the shortening of life span.",
keywords = "Calcitriol, Calcium, Cell volume, Phosphate, Sodium",
author = "Fischer, {Stephanie S.} and Kempe, {Daniela S.} and Leibrock, {Christina B.} and Rexhep Rexhepaj and Balasaheb Siraskar and Boini, {Krishna M.} and Ackermann, {Teresa F.} and Michael F{\"o}ller and Berthold Hocher and Rosenblatt, {Kevin P.} and Makoto Kuro-o and Florian Lang",
year = "2010",
month = "11",
doi = "10.1152/ajprenal.00233.2010",
language = "English (US)",
volume = "299",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Hyperaldosteronism in klotho-deficient mice

AU - Fischer, Stephanie S.

AU - Kempe, Daniela S.

AU - Leibrock, Christina B.

AU - Rexhepaj, Rexhep

AU - Siraskar, Balasaheb

AU - Boini, Krishna M.

AU - Ackermann, Teresa F.

AU - Föller, Michael

AU - Hocher, Berthold

AU - Rosenblatt, Kevin P.

AU - Kuro-o, Makoto

AU - Lang, Florian

PY - 2010/11

Y1 - 2010/11

N2 - Klotho is a membrane protein participating in the inhibitory effect of FGF23 on the formation of 1,25-dihydroxyvitamin-D3 [1,25(OH) 2D3]. It participates in the regulation of renal tubular phosphate reabsorption and stimulates renal tubular Ca2+ reabsorption. Klotho hypomorphic mice (klothohm) suffer from severe growth deficit, rapid aging, and early death, events largely reversed by a vitamin D-deficient diet. The present study explored the role of Klotho deficiency in mineral and electrolyte metabolism. To this end, klotho hm mice and wild-type mice (klotho+/+) were subjected to a normal (D+) or vitamin D-deficient (D-) diet or to a vitamin D-deficient diet for 4 wk and then to a normal diet (D-/+). At the age of 8 wk, body weight was significantly lower in klotho hmD+ mice than in klotho+/+D+ mice, klothohmD- mice, and klothohmD-/+ mice. Plasma concentrations of 1,25(OH)2D3, adrenocorticotropic hormone (ACTH), antidiuretic hormone (ADH), and aldosterone were significantly higher in klothohmD+ mice than in klotho+/+D+ mice. Plasma volume was significantly smaller in klothohmD-/+ mice, and plasma urea, Ca2+, phosphate and Na+, but not K+ concentrations were significantly higher in klothohmD+ mice than in klotho+/+D+ mice. The differences were partially abrogated by a vitamin D-deficient diet. Moreover, the hyperaldosteronism was partially reversed by Ca2+-deficient diet. Ussing chamber experiments revealed a marked increase in amiloride-sensitive current across the colonic epithelium, pointing to enhanced epithelial sodium channel (ENaC) activity. A salt-deficient diet tended to decrease and a salt-rich diet significantly increased the life span of klothohmD+ mice. In conclusion, the present observation disclose that the excessive formation of 1,25(OH)2D 3 in Klotho-deficient mice results in extracellular volume depletion, which significantly contributes to the shortening of life span.

AB - Klotho is a membrane protein participating in the inhibitory effect of FGF23 on the formation of 1,25-dihydroxyvitamin-D3 [1,25(OH) 2D3]. It participates in the regulation of renal tubular phosphate reabsorption and stimulates renal tubular Ca2+ reabsorption. Klotho hypomorphic mice (klothohm) suffer from severe growth deficit, rapid aging, and early death, events largely reversed by a vitamin D-deficient diet. The present study explored the role of Klotho deficiency in mineral and electrolyte metabolism. To this end, klotho hm mice and wild-type mice (klotho+/+) were subjected to a normal (D+) or vitamin D-deficient (D-) diet or to a vitamin D-deficient diet for 4 wk and then to a normal diet (D-/+). At the age of 8 wk, body weight was significantly lower in klotho hmD+ mice than in klotho+/+D+ mice, klothohmD- mice, and klothohmD-/+ mice. Plasma concentrations of 1,25(OH)2D3, adrenocorticotropic hormone (ACTH), antidiuretic hormone (ADH), and aldosterone were significantly higher in klothohmD+ mice than in klotho+/+D+ mice. Plasma volume was significantly smaller in klothohmD-/+ mice, and plasma urea, Ca2+, phosphate and Na+, but not K+ concentrations were significantly higher in klothohmD+ mice than in klotho+/+D+ mice. The differences were partially abrogated by a vitamin D-deficient diet. Moreover, the hyperaldosteronism was partially reversed by Ca2+-deficient diet. Ussing chamber experiments revealed a marked increase in amiloride-sensitive current across the colonic epithelium, pointing to enhanced epithelial sodium channel (ENaC) activity. A salt-deficient diet tended to decrease and a salt-rich diet significantly increased the life span of klothohmD+ mice. In conclusion, the present observation disclose that the excessive formation of 1,25(OH)2D 3 in Klotho-deficient mice results in extracellular volume depletion, which significantly contributes to the shortening of life span.

KW - Calcitriol

KW - Calcium

KW - Cell volume

KW - Phosphate

KW - Sodium

UR - http://www.scopus.com/inward/record.url?scp=78349269471&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78349269471&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00233.2010

DO - 10.1152/ajprenal.00233.2010

M3 - Article

VL - 299

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 5

ER -