SHORT-TERM TREATMENT WITH OLEOYL-ESTRONE IN LIPOSOMES (MERLIN-2) STRONGLY REDUCES THE EXPRESSION OF THE OB GENE IN YOUNG-RATS

Young female rats of 160-180 g were implanted with osmotic minipumps r eleasing 3.0 mu mol/day per kg of oleoyl-oestrone in liposomes (Merlin -2) into the bloodstream for up to 14 days. Merlin-2 induced a loss of appetite in the first days, later recovered, and a decrease in body w eight of 7% which contrasts with the 15% increase in controls during t he 2-week period. Neither plasma glucose nor urea was affected by trea tment, but liver glycogen increased by 50% in 14 days. Insulin decreas ed slightly with Merlin-2 treatment. Plasma corticotropin (ACTH) and c orticosterone showed a transient increase by day 6 of treatment. The e xpression of the ob gene in adipose tissue fell during the period stud ied to practically nil on day 14; circulating leptin levels decreased more than 70% from day 1 to day 14. Oestrone levels increased from 0.3 nM (controls) to a maintained 40-60 nM level for the rest of the expe riment. Oleoyl-oestrone levels first increased 4-fold, to decrease aga in to the initial levels on day 10, increasing later to 100-fold on da y 14. The three phases observed in food intake, weight loss and oleoyl -oestrone levels match fairly well, which supports the direct involvem ent of oleoyl-oestrone in body-weight control. However, the control of oleoyl-oestrone levels seems to be mediated in part by corticosterone . The practical disappearance of leptin synthesis coincides with the m assive accumulation of oleoyl-oestrone in plasma. The results presente d suggest the involvement of oleoyl-oestrone in the main mechanisms of control of body weight and its regulation by glucocorticoids and lept in.