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Abstract
The JCR:LA-corpulent rat is a useful experimental model for the obese-diabetic-dyslipidemic
syndrome that mimics the human condition and exhibits spontaneous development of atherosclerosis
and myocardial lesions. A 30-day treatment of 6-month-old rats with dexfenfluramine
1, 2.5, and 5 mg per kilogram decreased body weight through loss of adipose tissue
mass. The effect is caused primarily by the ability of dexfenfluramine to reduce food
intake. The maximum depression of food intake and greatest weight loss is seen during
the first 10 days of treatment in this experimental model; thereafter, body weight
stabilizes. However, during this period, there is a marked decrease in serum concentrations
of triglycerides, cholesterol, and insulin. Corpulent male rats were also treated
from 6 to 37 weeks of age with dexfenfluramine 2.5 mg/kg. This also produces a sustained
decrease in body weight and a decrease in circulating insulin concentrations. Preliminary
evidence demonstrates a substantial decrease in the incidence of necrotic myocardial
lesions produced by ischemic events. This study establishes that dexfenfluramine treatment
can decrease the severity of associated risk factors for cardiovascular disease, namely
obesity, diabetes, and dyslipidemias. Furthermore, we report the first evidence that
long-term treatment with dexfenfluramine can largely prevent the occurrence of myocardial
lesions and end-stage cardiovascular disease in this animal model prone to atherosclerosis.
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Zucker rats.Article info
Footnotes
☆Supported by the Alberta Heart and Stroke Foundation, the Medical Research Council of Canada, and Les Laboratoires Servier.
Identification
Copyright
© 1995 Published by Elsevier Inc.
