Effects of long-term d-fenfluramine treatment on energy metabolism in rats.
The effects of chronic intragastric administration of the anorectic agent d-fenfluramine on energy metabolism and nutrient concentrations were investigated at rest and during swimming. Rats were provided with permanent cannulas for blood sampling and intragastric administration of d-fenfluramine or saline. Energy expenditure and nutrient and hormone concentrations were determined. Under baseline conditions, d-fenfluramine increased carbohydrate utilization (14.2 vs. 7.0 mg/kg.min) and decreased fat oxidation (2.8 vs. 5.5 mg/kg.min). Plasma free fatty acid concentration was decreased (0.29 vs. 0.55 mmol/l) and lactate and insulin concentrations were increased after d-fenfluramine treatment (0.64 vs. 0.37 mmol/l and 61 vs. 33 mU/l, respectively). The shift in nutrient utilization also occurred during swimming. The exercise-induced increase in blood glucose was reduced after d-fenfluramine (+0.8 vs. +2.0 mmol/l). During swimming, free fatty acid, lactate and insulin concentrations were similar in the two groups. It is hypothesized that chronic d-fenfluramine treatment increases in the oxidation of carbohydrates and decreases the oxidation of fat as a result of a decrease in the transport of fatty acids over the mitochondrial membrane.
Benthem
L
L
Department of Medical Physiology, University of Groningen, Netherlands.
Scheurink
A J
AJ
Van der Leest
J
J
Leuvenink
H
H
Zijlstra
W G
WG
Steffens
A B
AB
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002151:Calorimetry; D002245:Carbon Dioxide / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005277:Fenfluramine / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D005082:Physical Exertion / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D002245:Carbon Dioxide; D005277:Fenfluramine; D019344:Lactic Acid