Effects of chronic administration of benfluorex to rats on the metabolism of corticosterone, glucose, triacylglycerols, glycerol and fatty acid.
(1) Rats were fed on diets enriched with sucrose, beef tallow or corn oil and treated for 11-16 days with 50 mg of benfluorex per kg of body weight. By these times the growth rate and food intake were not significantly different from those of control rats. (2) Benfluorex approximately halved the concentration of circulating triacylglycerol in rats fed the beef tallow or sucrose diets. (3) It did not significantly alter the total lipoprotein lipase activity in diaphragm, heart and adipose tissue. (4) The clearance of triacylglycerols from chylomicrons exhibited two t 1/2 values of about 0.6 and 6.9 min in rats fed the beef tallow diet. Benfluorex did not significantly alter these values. (5) Benfluorex did not significantly alter the rate of appearance of triacylglycerol in the blood of rats injected with Triton WR 1339 to block triacylglycerol uptake. It did, however, decrease the rise in circulating glucose which presumably resulted from the stress of the procedure. (6) Benfluorex decreased the extent and duration of the rise in serum corticosterone when rats maintained on the corn oil diet were fed acutely with fructose. It also decreased the circulating concentrations of glycerol, triacylglycerol and glucose after fructose feeding. (7) Rats fed on the corn oil diet and then treated with benfluorex had lower concentrations of circulating glucose, triacylglycerol, glycerol and fatty acids after being injected with 2-deoxyglucose. (8) It is proposed that some of the long-term hypoglycaemic and hypotriglyceridaemic effects of benfluorex could be mediated indirectly through changes in endocrine balance, perhaps via the serotonergic system and in particular, by decreasing the effects of stress hormones relative to insulin. The implications of these findings are discussed in relation to controlling metabolism in stress conditions and for the management of obesity, diabetes and atherosclerosis.
Brindley
D N
DN
Department of Biochemistry, University of Nottingham Medical School, Queen's Medical Centre, U.K.
Akester
H
H
Derrick
G P
GP
Irvine
C D
CD
Patmore
R D
RD
Spencer
H
H
Yule-Smith
A
A
Finnerty
C
C
Saxton
J
J
Macdonald
I A
IA
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005277:Fenfluramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000032:analysis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism
D001067:Appetite Depressants; D001786:Blood Glucose; D005227:Fatty Acids; D014280:Triglycerides; D005277:Fenfluramine; C001584:benfluorex; D008071:Lipoprotein Lipase; D005947:Glucose; D005990:Glycerol; D003345:Corticosterone