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Oleoyl-estrone given i.v.--incorporated in liposomes to mimic lipoprotein delivery--(Merlin-2) to normal weight rats, induces a dose-dependent weight loss. Analysis of body composition showed that body protein concentration was preserved and fat stores wasted. The respiratory quotient was consistent with the massive oxidation of body fat, since the diet contained practically no lipid. Appetite was affected by Merlin-2, and thus food intake showed a transient decrease. But oxygen consumption (and basal metabolic rates) was kept practically unchanged at the levels of the controls, i.e. higher than needed to oxidize the food ingested during the weight loss period. Brown adipose tissue uncoupling protein levels were proportionally preserved with a 2-week treatment, but it lost a substantial amount of lipid. In conclusion, Merlin-2 is a slimming agent with considerable potential given its powerful fat-wasting action, since it maintains thermogenesis despite lowered energy intake.

Weaned lean Zucker rats, 21-days old, were fed a cafeteria diet for 70 days. The cafeteria diet-obese rats were infused for 28 days (using miniosmotic pumps) with oleoyl-estrone in liposomes (Merlin-2) at a dose of 3.5 mmol/day.kg. Treatment resulted in loss of body weight: 11.6% (32 g), mainly due to fat: 20.0% (8.8 g), protein 5.2% (2.0 g) and water, preventing further increases in body weight and fat storage. Untreated rats increased their body weight: 7.6% (20 g), lipid: 10.5% (4.2 g) and protein: 13.2% (4.8 g). Plasma glucose, urea, triacylglycerols and cholesterol practically did not change with treatment. Merlin-2 decreased energy intake (to 83.7%) and energy output (to 87.7%, oxygen consumption). Decreases in nitrogen intake were partly compensated by higher digestive efficiency in treated rats. The size of the nitrogen gap was higher in treated rats than in controls. Essentially, protein balance was maintained and slimming was achieved with a minimal loss of body protein. Treated rats selected less carbohydrate, in particular sugars, in their diet than controls, but consumed practically the same protein and lipid. Treatment of cafeteria diet-fed rats with oleoylestrone in liposomes results in sustained loss of body weight--mainly lipid--for up to 28 days. Nitrogen balance is maintained overall. This is achieved through lower food intake--mainly of sugars--and less marked changes in energy output.