Female adult 9-week old Wistar rats were implanted with osmotic minipumps releasing for 14 days a
liposome suspension (controls) loaded with
oleoyl-estrone or other compounds of the
Merlin series:
estrone,
estradiol, oleoyl-
estradiol,
oleoyl-DHEA, stearoyl-
estrone, palmitoyl-
estrone, oleoyl-
diethylstilbestrol (DES),
estrone oleoyl-
ether and oleoyl-3-methoxy-estrone. All compounds were given at the same dose of 3.5 micromol/day x kg for 14 days. The effects on
body weight and food intake were recorded. In the case of
estrone esters, the body composition and
nitrogen balance were also determined. The chronic administration of
oleoyl-estrone in
liposomes to rats lowers food intake, maintaining energy consumption, thus inducing the active utilization of internal stores and, consequently, the loss of
body weight. This loss is mainly due to a decrease in fat, with lower proportional losses of water and a limited consumption of body
protein. Free
estrone had no effects on
body weight, but
estradiol did induce a decrease in
body weight, similar to that of oleoyl-
estradiol.
Oleoyl-DHEA had no significant effect on
body weight nor in food intake. Oleoyl-DES mimicked fairly well the effects of
oleoyl-estrone, both affecting food intake and
body weight. There was a relative lack of effects of
estrone oleoyl-
ether and of oleoyl-3-methoxy-estrone. The effects of
oleoyl-estrone were in part mimicked by stearoyl- and palmitoyl-
estrone, but their activity on a molar basis was lower, which suggests that the
fatty acid moiety significantly influences the activity of the
estrone ester as a slimming agent. The differences observed in the appetite suppression and overall slimming power of the stearoyl and palmitoyl-
estrone clearly indicate that the sites of action of the physiological agonist
oleoyl-estrone are at least two; the shape of the molecule, thus, may elicit a different degree of response of the systems controlled by
oleoyl-estrone levels. From this interaction a series of global effects are elicited, such as appetite suppression and the loss of body (fat) weight, the latter in part (but not only) due to decreased food intake. The results shown here also suggest that the overall configuration of fatty acyl-
estrone is more constrictive for its function as slimming agent than for its role as
appetite suppressant, which hints to different target organs or sites of action endowed with receptors showing different degrees of fulfilling the structural constrictions of the agonist molecule.