Oleoyl-estrone treatment affects the ponderostat setting differently in lean and obese Zucker rats

OBJECTIVE: To determine whether the slimming effects of treatment with oleo yl-estrone (OE) in liposomes of normal and obese rats are permanent, or dis appear as soon as the treatment with the drug ceased. This study was devise d to gain further knowledge on the postulated role of OE as a ponderostat s ignal, evaluating whether (in addition) it can lower the ponderostat settin g of the rat. DESIGN: The rats were infused for 14 d (using osmotic minipumps) with oleoy l-estrone in liposomes at a dose of 3.5 mu mol/kg - d, and were studied up to one month after the treatment ceased. SUBJECTS: Young adult lean controls (CL) or treated (TL) and obese controls (CO) or treated (TO) Zucker rats. MEASUREMENTS: Energy balance, blood glucose, liver glycogen, plasma insulin , leptin corticosterone, ACTH and estrone (free and total) concentrations, and expression of the OB gene in white adipose tissue (WAT). RESULTS: The loss of body weight caused by OE was recovered quickly in the TO, which gained weight at the same rate as the CO. TL rats, however remain ed at the low weight attained for one month after the treatment ceased. How ever, no differences were observed in calculated energy expenditure (EE) be tween the TL and TC rats once treatment had stopped. In TL and TO rats, liv er glycogen concentrations decreased to normal shortly after treatment ceas ed, and leptin expression and concentrations remained normal and unchanged after the end of OE treatment. In TO rats, plasma glucose, insulin and lept in were lower than in the CO. Total estrone concentrations decreased rapidl y in TL rats and more slowly in the TO, and free estrone followed a similar pattern. CONCLUSION: Continuous infusion of liposomes loaded with OE resulted in a d ecreased energy intake (El), maintenance of EE and the utilization of body fat reserves in lean and obese rats alike. This process ended in obese rats as soon as the infusion ceased, so that even when the levels of free and t otal estrone in plasma remained high, there was a marked (and relatively fa st) shift toward the basal situation, which translated into an increase in El, maintenance of estimated EE and a marked buildup of energy stores. In l ean rats, the effects of OE on leptin concentrations and OB gene expression persisted after infusion ended.