SUSTAINED DECREASES IN WEIGHT AND SERUM-INSULIN, GLUCOSE, TRIACYLGLYCEROL AND CHOLESTEROL IN JCR - LA-CORPULENT RATS TREATED WITH D-FENFLURAMINE

1 The effects of D-fenfluramine were studied in the JCR:LA-corpulent rat that is grossly obese, hyperphagic, hyperlipidaemic, hyperinsulinaemic and atherosclerosis-prone. 2 Daily doses of 1, 2.5 and 5 mg kg-1 of D-fenfluramine produced sustained decreases in body weight and food intake over a period of 30 days in 6 month old female rats fed ad libitum. This was accompanied by decreases in the circulating concentrations of glucose, triacylglycerol, free cholesterol and insulin. 3 Food restriction imposed by meal feeding also decreased circulating glucose, triacyglycerols, cholesterol and insulin and diminished the effect of D-fenfluramine on these parameters in male and female rats. 4 Addition of D-fenfluramine to drinking water to give a dose of about 0.25 mg kg-1 daily produced a sustained decrease in body weight and food intake of male and female rats over a nine week period. 5 The results show that the JCR:LA-corpulent rat is very sensitive to the pharmacological effects of D-fenfluramine. These rats should provide an appropriate animal model for determining the mechanisms of action of this anti-obesity agent and whether apparently beneficial changes in metabolism translate into long-term protection against premature atherosclerosis.