TISSUE-SPECIFIC AND GENDER-SPECIFIC MODULATION OF LIPOPROTEIN-LIPASE IN INTACT AND GONADECTOMIZED RATS TREATED WITH DL-FENFLURAMINE

This study evaluated the respective and interactive effects of chronic dl-fenfluramine treatment, an anorectic serotoninergic agonist, and g onadectomy on lipoprotein lipase activity in adipose tissue and skelet al muscle. Male and female Sprague-Dawley rats were gonadectomised. Th ese as well as intact animals were treated with dl-fenfluramine or a p lacebo for 28 days. Gonadectomy brought about an increase in final bod y weight of females (16-18%, P < 0.0001), but a decrease in that of ma le animals (9-13%, P < 0.001). These changes were proportional to thos e of food intake. The increase in body weight of gonadectomised female rats was paralleled by that of retroperitoneal adipose tissue and vas tus lateralis muscle weights, whereas in male rats, gonadectomy dimini shed 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 wa s unaffected by gonadectomy in both genders. Treatment with dl-fenflur amine 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). Th e drug remained without effect on muscle weight and lipoprotein lipase activity in either gender. Thus removal of gonadal steroids had diver gent effects on LPL activity with regard to gender and tissue. In addi tion, dl-fenfluramine treatment was followed by decreased enzyme activ ity in adipose tissue, but not in muscle, this pattern being independe nt of the nature or presence of gonadal steroids. Lipoprotein lipase a ctivity in adipose tissue was strongly associated with food intake and adipose mass. The findings suggest that the direct or indirect modula tion of lipoprotein lipase by gonadal steroids and that by dl-fenflura mine are independent from each other.