Lipostatic and ischymetric mechanisms originate dexfenfluramine-induced anorexia

Rats treated with physiological saline or dexfenfluramine (Isoméride, Laboratoires SERVIER, Neuilly, France) (dF), 1.75, 3.50, and 7.00 mg/kg, were studied in a computer-controlled open-circuit metabolic chamber, in which temperature was regulated at 24 degrees C. Total metabolic rate (TMR), respiratory quotient (RQ), locomotor activity (LA), energy cost of LA, and thus, locomotor free metabolic rate, were scanned at 10-second intervals throughout 22-hour uninterrupted recording sessions. The feeding pattern was also measured in relation to the dF-induced changes in the above parameters. It was found that dF induced a sustained decrease in TMR and RQ, while periodically enhancing the increase in TMR and RQ produced by the periods of LA. All phenomena occurred in a dose-dependent fashion. Anorexia was also increased as a function of the dF treatments and metabolic changes. It is concluded that dF-induced anorexia may be related to the enhanced release and utilisation of free fatty acids (lipostatic mechanism), and/or to the enhancement of metabolic rate during locomotor activity (ischymetric mechanism). In addition, it appeared that the increased prandial thermogenesis, previously reported from the measurement of changes in TMR, may be due to the dF-induced increase in the energy cost of LA, rather than to an effect of feeding per se. Indeed, in our experimental conditions, it was measured that the energetic cost of LA accounted for more than 60% of the periprandial increase in TMR.