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Cited by 57Cardiovascular Function and Risk FactorsCardiac Fibrosis and RemodelingCardiovascular Disease and Adiposity

Cardiovascular Abnormalities in Transgenic Mice With Reduced Brown Fat: An Animal Model of Human Obesity

Cittadini, Antonio, Mantzoros, Christos S., Hampton, Thomas G., Travers, Kerry E., Katz, Sarah E., Morgan, James P., Flier, Jeffrey S., Douglas, Pamela S.·1999·Circulation
DOI 10.1161/01.cir.100.21.2177
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Abstract

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. Methods and 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 · kg −1 · 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.

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Crossref · 10.1161/01.cir.100.21.2177

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38 of 38 references verified0 citation errors · 0 not checkable

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  • Increased interstitial fibrosis occurs in the hearts of Zucker (fa/fa) rats and UCP-DTA mice.

    “Increased interstitial fibrosis has been described in the hearts of Zucker (fa/fa) rats (350, 394) and in UCP-DTA mice (54).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [54]

  • UCP-DTA mice have a modest increase in blood pressure, eccentric LVH (with increased LV chamber size), and increased cardiac output.

    “These mice have a modest increase in blood pressure, eccentric LVH (with increased LV chamber size), and increased cardiac output (54).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [54]

  • In UCP-DTA mice, functional recovery following low-flow ischemia was impaired.

    “In UCP-DTA mice, functional recovery following low-flow ischemia was impaired (54).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [54]

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Authors
Cittadini, A., Mantzoros, C. S., Hampton, T. G., Travers, K. E., Katz, S. E., Morgan, J. P., Flier, J. S., & Douglas, P. S.
Affiliations
Beth Israel Deaconess Medical Center (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1999-11-23
Volume
100
Issue
21
Pages
2177-2183
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.100.21.2177
OpenAlex
W1968714501
Cited by
57
References
38
Citations by year
2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 6 · 2021: 4 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 2 · 2013: 3 · 2012: 1
FWCI
0.48
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01dk046930-10, 5r01hl031117-09)
  • National Heart, Lung, and Blood Institute (HL31117, HL-511307-01)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 46930)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
brown adipose tissue, obesity, transgenic mice, cardiovascular anomalies, left ventricular hypertrophy, eccentric remodeling, interstitial fibrosis, hypertension, cardiac output, myocardial ischemia, myocardial relaxation, obesity model
MeSH terms
Animals, Adipose Tissue, Brown, Disease Models, Animal, Echocardiography, Humans, Hypertension, Male, Mice, Transgenic, Obesity, Ventricular Function, Left, Hypertrophy, Left Ventricular, Mice

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