Short-term treatment with estrone oleate in liposomes (Merlin-2) does not affect the expression of the ob gene in Zucker obese rats

Young female Zucker fa/fa rats of 370-430 g were implanted with osmotic min ipumps releasing 3.5 mu mol/day.kg of estrone oleate in liposomes (Merlin-2 ) into the bloodstream for up to 14 days. Merlin-2 induced a sustained loss of appetite, and a decrease in body weight of 3.5%, which contrasts with t he 8.2% increase in controls during the period studied. Plasma insulin, glu cose and urea decreased, and liver glycogen increased with Merlin-2 treatme nt. Plasma ACTH and corticosterone increased to a maximum at the end of the experiment. The expression of the ob gene in adipose tissue was unchanged, and plasma leptin levels were also unchanged by treatment. Estrone levels increased more than 1500-fold, and estrone oleate rose 100-fold during trea tment. The fact that estrone oleate had no effect on the leptin levels or e xpression in obese rats, in contrast with the marked inhibition observed in the lean suggests that the functionality of the leptin receptor is essenti al for estrone oleate inhibition of the ob gene. This also suggests that le ptin may control ob gene expression in white adipose tissue and that estron e oleate may activate this process. The slimming effect of estrone oleate i s, thus, not directly dependent on leptin, since both normoleptinemic and h yperleptinemic animals lose fat following treatment nor are the effects on appetite and energy expenditure mediated by leptin. However, leptin levels and the expression of the ob gene are directly linked with estrone oleate f unction. A possible involvement of leptin in estrone oleate action is postu lated. The results support the participation of estrone oleate in the contr ol of body weight and hint at the complexity of its regulation by leptin an d glucocorticoids.