DEXFENFLURAMINE INHIBITS CATECHOLAMINE STIMULATED IN-VITRO LIPOLYSIS IN HUMAN FAT-CELLS

OBJECTIVE: To investigate the effect of dexfenfluramine (d-F) on basal and isoproterenol stimulated lipolysis in human fat cells in vitro. D ESIGN: Adipocytes were incubated in Krebs-Ringer-Hepes buffer either w ith 10(-6) M or 10(-7) M isoproterenol alone, with 0.02-200 mu g/ml (7 4.7 nmol/l-747 mu mol/l) of d-F or both. MEASUREMENTS: Glycerol releas e at 2 h incubation time was measured as an estimate for lipolysis. RE SULTS: The addition of d-F did not significantly influence basal lipol ysis of 58.6 nmol/2 h. Stimulation by 10(-6) M and 10(-7) M isoprotere nol increased glycerol release to 92.5 nmol/2 h and 83.4 nmol/2 h, res pectively. Adding increasing doses of d-F and 10(-6) M isoproterenol c aused a dose-dependent inhibition of isoproterenol stimulated lipolysi s. Glycerol release was significantly decreased to 84.1 nmol/2 h at 20 mu g/ml, to 77.8 nmol/2 h at 60 mu g/ml and to 61.9 nmol/2 h at 200 m u g/dl d-F. Glycerol release induced by 10(-7) M isoproterenol was sig nificantly inhibited to 69.7 nmol/2 h at 20 mu g/ml, to 61.5 nmol/2 h at 60 mu g/ml and to 51.9 nmol/2 h at 200 mu g/ml d-F. 50% inhibition occurred at 80 mu g/ml d-F with 10(-6) M isoproterenol and at 28 mu g/ ml with 10(-7) M isoproterenol. CONCLUSION: d-F may decrease the relea se of free fatty acids from adipose tissue. This would lead to a reduc ed flux to the liver and may partly account for the triglyceride lower ing effect of d-F in obese subjects.