Cardiovascular abnormalities in transgenic mice with reduced brown fat - An animal model of human obesity

Background-A new model of murine obesity has recently been developed throug h transgenic ablation of brown adipose tissue that manifests typical metabo lic complications of obesity, including insulin resistance and non-insulin- dependent diabetes mellitus. The cardiovascular phenotype has not been defi ned. Methods and Results-Transthoracic echocardiography, aortic catheterization, isolated whole-heart studies, and morphometric histology defined cardiac s tructure and function in 30 transgenic mice with reduced brown fat and 30 m atched wild-type controls. Obesity was indicated by a 77% increase in body weight and was accompanied by elevated systemic pressures (mean aortic bloo d pressure 85+/-1 versus 66+/-2 mm Hg; P<0.01), left ventricular dilation a nd hypertrophy (mass/body weight 4.0+/-0.2 versus 2.7+/-0.3 mg/g; P<0.01), and high cardiac output (cardiac index 3.2+/-0.4 versus 2.4+/-0.1 mL.kg(-1) .min(-1); P<0.01). Baseline functional parameters assessed in vitro were no t different, but after imposition of zero-flow ischemia, significant relaxa tion impairment developed in obese mice. Although morphometically determine d myocyte diameters were similar, the percentage of interstitial fibrosis w as significantly increased in transgenic mice compared with wild-type contr ols (7.5+/-2% versus 4.2+/-0.2%; P<0.01). Conclusions Transgenic ablation of brown adipose tissue is associated not o nly with obesity but also with systemic hypertension, left ventricular hype rtrophy with eccentric remodeling and fibrosis, and high cardiac output, a unique constellation of findings strikingly similar to that seen in human o besity. Mice with reduced brown fat may serve as a new model for the cardio vascular morbid complications associated with obesity in humans.