Effect of the slimming agent oleoyl-estrone in liposomes on the body weight of Zucker obese rats

Abstract

OBJECTIVE: To determine whether the mechanisms by which estrone acyl-esters carried by lipoproteins induce the loss of body fat can affect Zucker fa/fa rats, since they are hyperphagic and could not eliminate excess energy through thermogenesis, two aspects essential for the slimming effect of oleoyl-estrone in normal rats. DESIGN: The rats were infused for 28 d (osmotic minipumps) with oleoyl-estrone in liposomes (Merlin-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 chemistry. 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 % (15.5 g) O and water, preventing further increases in body weight and fat 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 cholesterol decreased; O showed no changes in plasma composition. In all rats, food intake decreased with treatment, and heat production (oxygen consumption) was unchanged (L) or slightly decreased (O). Energy expenditure per unit of fat-free mass remained unchanged. Protein balance was maintained in all groups; slimming was achieved without loss of body protein. CONCLUSION: Treatment of genetically obese rats with oleoyl-estrone in liposomes (Merlin-2) results in sustained loss of body weight – mainly lipid, sparing protein – for up to 28 d, essentially preventing further increase in body weight and accumulation of lipid and protein. This is achieved through lower food intake and relatively small changes (if any) in energy expenditure.