Clustering of Cardiovascular Risk Factors Mimicking the Human Metabolic Syndrome X in eNOS Null Mice

Swiss Med Wkly. 2003 Jun 28;133(25-26):360-3.

Abstract

Aims/hypothesis: The metabolic syndrome comprises a clustering of cardiovascular risk factors but the underlying mechanism is not known. Mice with targeted disruption of endothelial nitric oxide synthase (eNOS) are hypertensive and insulin resistant. We wondered, whether eNOS deficiency in mice is associated with a phenotype mimicking the human metabolic syndrome.

Methods and results: In addition to arterial pressure and insulin sensitivity (euglycaemic hyperinsulinaemic clamp), we measured the plasma concentration of leptin, insulin, cholesterol, triglycerides, free fatty acids, fibrinogen and uric acid in 10 to 12 week old eNOS-/- and wild type mice. We also assessed glucose tolerance under basal conditions and following a metabolic stress with a high fat diet. As expected eNOS-/- mice were hypertensive and insulin resistant, as evidenced by fasting hyperinsulinaemia and a roughly 30 percent lower steady state glucose infusion rate during the clamp. eNOS-/- mice had a 1.5 to 2-fold elevation of the cholesterol, triglyceride and free fatty acid plasma concentration. Even though body weight was comparable, the leptin plasma level was 30% higher in eNOS-/- than in wild type mice. Finally, uric acid and fibrinogen were elevated in the eNOS-/- mice. Whereas under basal conditions, glucose tolerance was comparable in knock out and control mice, on a high fat diet, knock out mice became significantly more glucose intolerant than control mice.

Conclusions: A single gene defect, eNOS deficiency, causes a clustering of cardiovascular risk factors in young mice. We speculate that defective nitric oxide synthesis could trigger many of the abnormalities making up the metabolic syndrome in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / physiopathology*
  • Disease Models, Animal*
  • Glucose / metabolism
  • Hyperlipidemias / complications
  • Hyperlipidemias / metabolism*
  • Insulin Resistance / physiology
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / diagnosis
  • Metabolic Syndrome / physiopathology*
  • Mice
  • Mice, Mutant Strains
  • Nitric Oxide Synthase / deficiency*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Risk Factors

Substances

  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Glucose