Use of Fat-Fed Rats to Study the Metabolic and Vascular Sequelae of Obesity and -Adrenergic Antagonism
Abstract:Obesity-associated cardiovascular disease exerts profound human and monetary costs, creating a mounting need for cost-effective and relevant in vivo models of the complex metabolic and vascular interrelationships of obesity. Obesity is associated with endothelial dysfunction and inflammation. Free fatty acids (FFA), generated partly through -adrenergic receptor-mediated lipolysis, may impair endothelium-dependent vasodilation (EDV) by proinflammatory mechanisms. -Adrenergic antagonists protect against cardiovascular events by mechanisms not fully defined. We hypothesized that antagonists may exert beneficial effects, in part, by inhibiting lipolysis and reducing FFA. Further, we sought to evaluate the fat-fed rat as an in vivo model of obesity-induced inflammation and EDV. Control and fat-fed rats were given vehicle or antagonist for 28 d. Serum FFA were measured to determine the association to serum IL6, TNFα, and C-reactive protein and to femoral artery EDV. Compared with controls, fat-fed rats weighed more and had higher FFA, triglyceride, leptin, and insulin levels. Unexpectedly, in control and fat-fed rats, antagonism increased FFA, yet inflammatory cytokines were reduced and EDV was preserved. Therefore, reduction of FFA is unlikely to be the mechanism by which antagonists protect the endothelium. These results reflect the need for validation of ex vivo models of obesity-induced inflammation and endothelial dysfunction, concurrent with careful control of dietary fat composition and treatment duration.
Document Type: Research Article
Affiliations: 1: Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver, Colorado, USA; Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA. Melinda.Frye@colostate.edu 2: Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver, Colorado, Department of Pharmacology, University of South Alabama, Mobile, Alabama 3: Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado 4: Department of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado, Department of Medicine, University of South Alabama, Mobile, Alabama
Publication date: 2009-06-01
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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