OLEOYL-ESTRONE INDUCES THE LOSS OF BODY-FAT IN RATS

OBJECTIVE: Four experiments were devised to test the possible role of estrone fatty esters as adipose tissue signals carried by the blood wi thin lipoproteins. DESIGN: Oleoyl-estrone was synthesized and incorpor ated in liposomes; it was administered i.v. (to mimic lipoprotein deli very) for 14-day periods using implantable osmotic minipumps. The stud y included the finding of oleoyl-estrone in blood lipoproteins. the co rrelation of the effects on body weight to the dose and the uptake of labelled oleoyl-estrone by tissues, its internalization and disposal. SUBJECTS: Normal-weight Wistar female rates were used. Pooled human bl ood was used as source of HDL(3). MEASUREMENTS: Oleoyl-estrone was ide ntified in rat white adipose tissue and in human blood HDL(3) lipoprot ein fraction. Changes in body weight, food intake, oxygen consumption, respiratory quotient and nitrogen balance were measured in chronicall y injected rats. The uptake and hydrolysis of oleoyl-estrone by tissue s was also determined following its acute administration. RESULTS: Ole oyl-estrone induced a dose-dependent loss of weight, with decreased fo od intake. In 14 days, and compared with controls at the end of this p eriod. a dose of 0.78 mu mol/day induced the loss of 16.4 +/- 5.5% of body weight; the difference was maximal for doses of 15 mu mol/day or higher: 24.7 +/- 3.1%. Under oleoyl-estrone treatment, body protein wa s preserved (positive nitrogen balances) and fat stores were wasted: l owered respiratory quotient, and deficit in energy balance; a dose of 0.78 mu mol/day induced the loss of 9.6 +/- 2.2 g of total body lipids in 14 days. Most of oleoyl-estrone taken up by tissues was hydrolysed ; however, in part it reached intact the cell nucleus of incubated adi pocytes. Oleoyl-estrone effects were different from those of free estr one. CONCLUSION: A lipophilic pathway for oleoyl-estrone transport by lipoproteins is postulated, allowing chemical communication between ti ssues. Oleoyl-estrone may be directly involved in the control of body weight.