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 through transgenic ablation of brown adipose tissue that manifests typical metabolic complications of obesity, including insulin resistance and non-insulin-dependent diabetes mellitus. The cardiovascular phenotype has not been defined.


RESULTS
Transthoracic echocardiography, aortic catheterization, isolated whole-heart studies, and morphometric histology defined cardiac structure and function in 30 transgenic mice with reduced brown fat and 30 matched wild-type controls. Obesity was indicated by a 77% increase in body weight and was accompanied by elevated systemic pressures (mean aortic blood pressure 85+/-1 versus 66+/-2 mm Hg; P<0.01), left ventricular dilation and 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 x kg(-1) x min(-1); P<0.01). Baseline functional parameters assessed in vitro were not different, but after imposition of zero-flow ischemia, significant relaxation impairment developed in obese mice. Although morphometrically determined myocyte diameters were similar, the percentage of interstitial fibrosis was significantly increased in transgenic mice compared with wild-type controls (7.5+/-2% versus 4. 2+/-0.2%; P<0.01).


CONCLUSIONS
Transgenic ablation of brown adipose tissue is associated not only with obesity but also with systemic hypertension, left ventricular hypertrophy with eccentric remodeling and fibrosis, and high cardiac output, a unique constellation of findings strikingly similar to that seen in human obesity. Mice with reduced brown fat may serve as a new model for the cardiovascular morbid complications associated with obesity in humans.
Cittadini
A
A
Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. cittadin@unina.it
Mantzoros
C S
CS
Hampton
T G
TG
Travers
K E
KE
Katz
S E
SE
Morgan
J P
JP
Flier
J S
JS
Douglas
P S
PS
D002001:Adipose Tissue, Brown / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D006801:Humans; D006973:Hypertension / Q000209:etiology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology*; D016277:Ventricular Function, Left