Oleoyl-estrone induces the massive loss of body weight in Zucker fa/fa rats fed a high-energy hyperlipidic diet

To rest whether oleoyl-estrone plus a hyperlipidic diet affects body weight in Zucker fa/fa rats, 13-week-old male Zucker obese (fa/fa) rats initially weighing 440-470 g were used. They were fed for 15 days with a powdered hy perlipidic diet (16.97 MJ/kg metabolizable energy) in which 46.6% was lipid -derived and 16.1% was protein-derived energy and containing 1.23 +/- 0.39 mu mol/kg of fatty-acyl esters of estrone. This diet was supplemented with added oleoyl-estrone to produce a diet with 33.3 (mu mol/kg of fatty-acyl e strone. Oral administration of oleoyl-estrone in a hyperlipidic diet (at a mean dose of 0.5 mu mol.kg(-1).d(-1)) resulted in significant losses of fat , energy and, ultimately, weight. Treatment induced the maintenance of ener gy expenditure combined with lower food intake, creating an energy gap that was filled with internal fat stores while preserving body protein, in cont rast with the marked growth of controls fed the hyperlipidic diet. Treatmen t of genetically obese rats with a hyperlipidic diet containing additional oleoyl-estrone resulted in the loss of fat reserves with scant modification of other metabolic parameters, except for lower plasma glucose and insulin levels. The results agree with the postulated role of oleoyl-estrone as a ponderostat signal. (C) Elsevier Science Inc. 2000. All rights reserved.