EFFECT OF THE SLIMMING AGENT OLEOYL-ESTRONE IN LIPOSOMES ON THE BODY-WEIGHT OF ZUCKER OBESE RATS

OBJECTIVE: To determine whether the mechanisms by which estrone acyl-e sters carried by lipoproteins induce the loss of body fat can affect Z ucker fa/fa rats, since they are hyperphagic and could not eliminate e xcess energy through thermogenesis, two aspects essential for the slim ming effect of oleoyl-estrone in normal rats. DESIGN: The rats were in fused for 28 d (osmotic minipumps) with oleoyl-estrone in liposomes (M erlin-2) at a dose of 3.5 mmol/day.kg. SUBJECTS: Lean (L) and obese (O ) Zucker rats. MEASUREMENTS: Body weight changes. Oxygen consumption, body composition [water, lipid, protein), nitrogen balance, plasma che mistry. RESULTS: Treatment resulted in loss of body weight: 12.0 % (28 g) L, 9.4 % (34 g) O, mainly due to fat: 37.5 % (10.8 g) L, 11.7 % (1 5.5 g) O and water, preventing further increases in body weight and fa t storage. Untreated rats increased their body weight: 10.5 % (24 g) L , 32.2 % (101 g) O and lipid stores: 20.3 % (5.9 g) L, 39.8 % (49.0 g) O, making the differences more marked. On day 28, glucose levels were maintained in all groups; in L,triacylglycerols increased and total c holesterol decreased; O showed no changes in plasma composition. In al l rats, food intake decreased with treatment, and heat production (oxy gen consumption) was unchanged (L) or slightly decreased (O). Energy e xpenditure per unit of fat-free mass remained unchanged. Protein balan ce was maintained in all groups; slimming was achieved without Toss of body protein. CONCLUSION: Treatment of genetically obese rats with ol eoyl-estrone in liposomes (Merlin-2) results in sustained loss of body weight-mainly lipid, sparing protein-for up to 28 d, essentially prev enting further increase in body weight and accumulation of lipid and p rotein. This is achieved through lower food intake and relatively smal l changes (if any) in energy expenditure.