Effect of adrenalectomy on the slimming activity of liposome-carried oleoyl-estrone in the rat

Abstract

OBJECTIVE: To determine the extent of glucocorticoid counter-regulatory control in the slimming action of oleoyl-estrone.

DESIGN: Control and adrenalectomized rats were subjected to a seven-day treatment with 3.5 μmol/kg/d oleoyl-estrone in liposomes injected i.v. continuously by implanted osmotic minipumps.

SUBJECTS: Sham-operated control and adrenalectomized lean Zucker rats.

MEASUREMENTS: Body weight and food intake; plasma glucose, urea, insulin, leptin and corticosterone; liver glycogen.

RESULTS: Treatment with oleoyl-estrone resulted in decreases in body weight and in food intake, as well as in circulating glucose, insulin 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 disappearance of plasma leptin and liver glycogen and a 3-fold rise in circulating urea. Food intake decreased sharply, which resulted in the exhaustion of energy reserves.

CONCLUSION: The results presented here, strongly support the hypothesis that glucocorticoids play an important role in the modulation of oleoyl-estrone-induced imbalance of energy intake and expenditure. The large effect of oleoyl-estrone on glucose, glycogen- and protein-derived (urea levels) energy in adrenalectomized rats, provides more evidence for the assumed protective role of glucocorticoids against the oleoyl-estrone-induced net loss of energy reserves. The results also show the powerful destabilizing effects of unchecked oleoyl-estrone on energy balance.