Tissue- and gender-specific modulation of lipoprotein lipase in intact and gonadectomised rats treated with dl-fenfluramine.
This study evaluated the respective and interactive effects of chronic dl-fenfluramine treatment, an anorectic serotoninergic agonist, and gonadectomy on lipoprotein lipase activity in adipose tissue and skeletal muscle. Male and female Sprague-Dawley rats were gonadectomised. These as well as intact animals were treated with dl-fenfluramine or a placebo for 28 days. Gonadectomy brought about an increase in final body weight of females (16-18%, P < 0.0001), but a decrease in that of male animals (9-13%, P < 0.001). These changes were proportional to those of food intake. The increase in body weight of gonadectomised female rats was paralleled by that of retroperitoneal adipose tissue and vastus lateralis muscle weights, whereas in male rats, gonadectomy diminished muscle weight only. Lipoprotein lipase activity was doubled (P < 0.0001) by gonadectomy in adipose tissue of female rats, but remained unaltered by the surgery in male animals. Enzyme activity in muscle was unaffected by gonadectomy in both genders. Treatment with dl-fenfluramine reduced weight gain in males and females, whether they had been gonadectomised or not. A concomitant reduction was observed in adipose tissue mass and lipoprotein lipase activity, which was reduced to 50-65% of the activity measured in placebo-treated animals (P < 0.01). The drug remained without effect on muscle weight and lipoprotein lipase activity in either gender. Thus removal of gonadal steroids had divergent effects on LPL activity with regard to gender and tissue. In addition, dl-fenfluramine treatment was followed by decreased enzyme activity in adipose tissue, but not in muscle, this pattern being independent of the nature or presence of gonadal steroids.(ABSTRACT TRUNCATED AT 250 WORDS)
Deshaies
Y
Y
Department of Physiology, School of Medicine, Laval University, Québec, Canada.
Dagnault
A
A
Boivin
A
A
Richard
D
D
D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D002369:Castration; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000033:anatomy & histology / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D012727:Sex Characteristics
D007328:Insulin; D005277:Fenfluramine; D008071:Lipoprotein Lipase