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.


METHODS
Adipocytes were incubated in Krebs-Ringer-Hepes buffer either with 10(-6) M or 10(-7) M isoproterenol alone, with 0.02-200 micrograms/ml (74.7 nmol/l-747 mumol/l) of d-F or both.


METHODS
Glycerol release at 2 h incubation time was measured as an estimate for lipolysis.


RESULTS
The addition of d-F did not significantly influence basal lipolysis of 58.6 nmol/2 h. Stimulation by 10(-6) M and 10(-7) M isoproterenol increased glycerol release to 92.5 nmol/2 h and 83.4 nmol/2 h, respectively. Adding increasing doses of d-F and 10(-6) M isoproterenol caused a dose-dependent inhibition of isoproterenol stimulated lipolysis. Glycerol release was significantly decreased to 84.1 nmol/2 h at 20 micrograms/ml, to 77.8 nmol/2 h at 60 micrograms/ml and to 61.9 nmol/2 h at 200 micrograms/dl d-F. Glycerol release induced by 10(-7) M isoproterenol was significantly inhibited to 69.7 nmol/2 h at 20 micrograms/ml, to 61.5 nmol/2 h at 60 micrograms/ml and to 51.9 nmol/2 h at 200 micrograms/ml d-F. 50% inhibition occurred at 80 micrograms/ml d-F with 10(-6) M isoproterenol and at 28 micrograms/ml with 10(-7) M isoproterenol.


CONCLUSIONS
d-F may decrease the release of free fatty acids from adipose tissue. This would lead to a reduced flux to the liver and may partly account for the triglyceride lowering effect of d-F in obese subjects.
Department of Medicine II, University of Munich, Germany.
W O
WO
Richter
M G
MG
Donner
P
P
Schwandt
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001067:Appetite Depressants / Q000494:pharmacology*; D002395:Catecholamines / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged
D001067:Appetite Depressants; D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D005277:Fenfluramine; D007545:Isoproterenol; D005990:Glycerol