Resistance of mice lacking the serum- and glucocorticoid-inducible kinase SGK1 against salt-sensitive hypertension induced by a high-fat diet

• Published in: American journal of physiology. Renal physiology Vol. 291; no. 6; pp. F1264 - F1273
• Main Authors: Huang, Dan Yang, Boini, Krishna M, Osswald, Hartmut, Friedrich, Björn, Artunc, Ferruh, Ullrich, Susanne, Rajamanickam, Jeyaganesh, Palmada, Monica, Wulff, Peer, Kuhl, Dietmar, Vallon, Volker, Lang, Florian
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.12.2006
• Subjects: Aldosterone - blood; Animal Feed; Animals; Blood pressure; Blood Pressure - physiology; Body Weight; Dietary Fats - pharmacology; Drinking; Eating; Electrolytes - blood; Female; Hormones; Hypertension, Renal - chemically induced; Hypertension, Renal - metabolism; Hypertension, Renal - physiopathology; Hypoglycemia - metabolism; Hypoglycemia - physiopathology; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Insulin; Insulin - blood; Kidneys; Kinases; Lipids - blood; Male; Mice; Mice, Inbred Strains; Mice, Knockout; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Rodents; Sodium Chloride, Dietary - pharmacology; Urine
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00299.2005

Mineralocorticoids enhance expression and insulin stimulates activity of the serum- and glucocorticoid-inducible kinase SGK1, which activates the renal epithelial Na+)channel (ENaC). Under a salt-deficient diet, SGK1 knockout mice (sgk1-/-) excrete significantly more NaCl than their wild-type littermates (sgk1+/+) and become hypotensive. The present experiments explored whether SGK1 participates in the hypertensive effects of a high-fat diet and high-salt intake. Renal SGK1 protein abundance of sgk1+/+ mice was significantly elevated after a high-fat diet. Under a control diet, fluid intake, blood pressure, urinary flow rate, and urinary Na+, K+, and Cl- excretion were similar in sgk1-/- and sgk1+/+ mice. Under a standard diet, high salt (1% NaCl in the drinking water for 25 days) increased fluid intake, urinary flow rate, and urinary Na+, K+, and Cl- excretion similarly in sgk1-/- and sgk1+/+ mice without significantly altering blood pressure. A high-fat diet alone (17 wk) did not significantly alter fluid intake, urinary flow rate, urinary Na+, K+, or Cl- excretion, or plasma aldosterone levels but increased plasma insulin, total cholesterol, triglyceride concentrations, and systolic blood pressure to the same extent in both genotypes. Additional salt intake (1% NaCl in the drinking water for 25 days) on top of a high-fat diet did not affect hyperinsulinemia or hyperlipidemia but increased fluid intake, urinary flow rate, and urinary NaCl excretion significantly more in sgk1-/- than in sgk1+/+ mice. Furthermore, in animals receiving a high-fat diet, additional salt intake increased blood pressure only in sgk1+/+ mice (to 132 +/- 3 mmHg) but not in sgk1-/- mice (120 +/- 4 mmHg). Thus lack of SGK1 protects against the hypertensive effects of a combined high-fat/high-salt diet.