Daily oral oleoyl-estrone gavage induces a dose-dependent loss of fat in Wistar rats

Objective: To establish whether single daily oral doses of oleoyl-estrone r esult in dose-dependent slimming effects on normal weight rats, and to dete rmine the changes in energy parameters induced by this treatment. Research Methods and Procedures: The effects of a daily oral gavage of oleo yl-estrone (0, 0.2, 0.5, 1, 2, 5, 10, and 20 mu mol/kg per day) in 0.2 mi o f sunflower oil given over a 10-day period were studied in groups, each of which contained six adult female Wistar rats initially weighing 190 to 230 g. A group of intact control rats receiving no gavage was included for comp arison. Body weight and food intake were measured daily. Rats were killed o n day 10 of treat ment, and body composition (protein nitrogen, lipids, and water), liver lipids, and plasma parameters (glucose, triacylglycerols, to tal cholesterol, free fatty acids, 3-hydroxybutyrate, urea, aspartate, alan ine transaminases, insulin, leptin, and free and acyl-estrone) were measure d. Results: The administration of oleoyl-estrone resulted in a dose-dependent loss of body fat, because of a partly maintained energy expenditure combine d with decreased food intake. The differences in the energy budget were met by internal fat pools. The changes recorded did not affect the levels of t he main plasma energy homeostasis indicators: unaltered glucose, triacylgly cerols, free fatty acids, 3hydroxybutyrate, and urea. Protein was accrued e ven under conditions of severe lipid store drainage. There were no changes in transaminases. No lipid accumulation was recorded in the liver. Plasma i nsulin and leptin levels decreased with increased oleoyl-estrone doses, whe reas the levels of free and esterified estrone increased with treatment, al though not in proportion to the dose received. Discussion: Oral treatment with oleoyl-estrone resulted in the specific dos e-related loss of fat reserves with little change to other metabolic parame ters. These results agree with the postulated role of oleoyl-estrone as a p onderostat signal.