Oral oleoyl-estrone induces the rapid loss of body fat in Zucker lean ratsfed a hyperlipidic diet

OBJECTIVE: To test whether oleoyl-estrone affects body weight when given or ally, which may help curtail the secondary growth-boosting effects of deriv ed estrone. DESIGN: The rats were fed for 15 days with a powdered hyperlipidic diet (16 .97 MJ/kg metabolizable energy) in which 46.6% was lipid-derived and 16.1% protein-derived energy (HL group), containing 1.23+/-0.39 mu mol/kg of fatt y-acyl esters of estrone. This diet was supplemented with additional oleoyl -estrone to produce diets with 2.5 mu mol/kg (diet OE2.5), 4.4 mu mol/kg (d iet OE4.4), and 33.3 mu mol/kg content in fatty-acyl estrone (diet OE33). SUBJECTS: Twelve-week old female Zucker lean (Fa/?) rats initially weighing 200 - 235 g. MEASUREMENTS: Food intake and body weight changes; urine and droppings prod uction and nitrogen content, Body composition (water, lipid, protein) and t otal energy. Energy and nitrogen balances. Plasma chemistry including free amino acids. RESULTS: Oral administration of oleoyl-estrone in a hyperlipidic diet resul ted in significant losses of fat, energy and, ultimately, weight, which wer e dependent on the dose of oleoyl-estrone ingested. Treatment induced the m aintenance of energy expenditure combined with lower food intake, creating an energy gap that was filled with internal fat stores whilst preserving bo dy protein. The decrease in food intake was not a consequence of food avers ion but of diminished appetite. Energy expenditure was practically constant for all groups except for the OE33, which showed Values about 25% lower th an the controls. In most of the groups studied, there was a net protein dep osition in spite of severe lipid and energy drainage. Amino acid levels agr eed with this N-sparing shift. In spite of lowered energy intake, the N bal ance was positive or near zero in all groups, with a sizeable N-gap in cont rols and in lower-dose groups that disappeared in the OE33 group. CONCLUSION: Treatment of rats with a hyperlipidic diet containing added ole oyl-estrone resulted in the dose-related loss of fat reserves with scant mo dification of other metabolic parameters and preservation of body protein. The results agree with the postulated role of oleoyl-estrone as a ponderost at signal and open the way for its development as anti-obesity drug.