Effect of qualitative differences in dietary fat on dexfenfluramine mediated depression of food intake and serotonin metabolism

Abstract

Previously, we showed that rats fed greater amounts of dietary saturated fat select more protein and less carbohydrate than rats fed diets with lesser amounts. Four experiments were designed to determine if dietary fat-induced differences in selection behavior were mediated by the serotonergic system. All diets were isoenergetic with 20% (w/w) fat. In experiment I, rats were fed diets (24% protein, 40% carbohydrate, 20% fat) containing 9%, 8%, or 3% saturated fat. Dexfenfluramine (0, 0.6 and 1.2 mg/kg) resulted in a dose-dependent decrease in food intake in all groups at 1, 2, and 16 hours after food presentation ( P<0.0006). In addition, there was a significant diet by drug interaction at each time interval ( P<0.05), indicating the effect was not independent of dietary fat composition. When rats selected from high-protein low-carbohydrate and low-protein high-carbohydrate diets containing 9% or 3% saturated fat (total fat content of all diets remained 20% (w/w)), dexfenfluramine resulted in decreased intake of food, protein, and carbohydrate in both groups ( P<0.05). However, there was no significant diet by drug interaction at any time interval. Consumption of the low-protein high-carbohydrate diet was decreased more than consumption from the high-protein low-carbohydrate diet regardless of diet fat treatment after 1 or 2 hours of feeding. Serotonin turnover was assessed in experiments 3 and 4 using pargyline to block monoamine oxidase. There was no dietary fat by treatment effect on hypothalamic indoleamines or tryptophan when rats were fed single diets with a fixed protein/carbohydrate ratio, or when rats consumed selection diets. Thus, turnover rates were similar across diet fat treatments. The results of these experiments suggest that qualitative differences in dietary fat composition may influence the anorectic response to dexfenfluramine when rats are fed single diets with fixed protein/carbohydrate ratios, but that changes in steady-state serotonin metabolism or in serotonin turnover are not involved in the mechanism.