EFFECT OF ADRENALECTOMY ON THE SLIMMING ACTIVITY OF LIPOSOME-CARRIED OLEOYL-ESTRONE IN THE RAT

OBJECTIVE: To determine the extent of glucocorticoid counter-regulator y control in the slimming action of oleoylestrone. DESIGN: Control and adrenalectomized rats were subjected to a seven-day treatment with 3. 5 mu mol/kg/d oleoylestrone in liposomes injected i.v. continuously by implanted osmotic minipumps. SUBJECTS: Sham-operated control and adre nalectomized lean Zucker rats. MEASUREMENTS: Body weight and food inta ke; plasma glucose, urea, insulin, leptin and corticosterone; liver gl ycogen. RESULTS: Treatment with oleoyl-estrone resulted in decreases i n body weight and in food intake, as well as in circulating glucose, i nsulin and leptin, Combined adrenalectomy and oleoyl-estrone treatment resulted in a loss of almost 15% body weight in only seven days, with a severe drop in circulating glucose and insulin, almost total disapp earance of plasma leptin and liver glycogen and a 3-fold rise in circu lating urea. Food intake decreased sharply, which resulted in the exha ustion of energy reserves. CONCLUSION: The results presented here, str ongly support the hypothesis that glucocorticoids play an important ro le in the modulation of oleoyl-estrone-induced imbalance of energy int ake and expenditure. The large effect of oleoyl-estrone on glucose, gl ycogen- and protein-derived (urea levels) energy in adrenalectomized r ats, provides more evidence for the assumed protective role of glucoco rticoids against the oleoyl-estrone-induced net loss of energy reserve s. The results also show the powerful destabilizing effects of uncheck ed oleoyl-estrone on energy balance.