Oleoyl-estrone induces the loss of body fat in rats

Four experiments were devised to test the possible role of estrone fatty esters as adipose tissue signals carried by the blood within lipoproteins.Oleoyl-estrone was synthesized and incorporated in liposomes; it was administered i.v. (to mimic lipoprotein delivery) for 14-day periods using implantable osmotic minipumps. The study included the finding of oleoyl-estrone in blood lipoproteins, the correlations of the effects of body weight to the dose and the uptake of labelled oleoyl-estrone by tissues, its internalization and disposal.Normal-weight Wistar female rates were used. Pooled human blood was used as source of HDL3.Oleoyl-estrone was identified in rat white adipose tissue and in human blood HDL3 lipoprotein fraction. Changes in body weight, food intake, oxygen consumption, respiratory quotient and nitrogen balance were measured in chronically injected rats. The uptake and hydrolysis of oleoyl-estrone by tissues was also determined following its acute administration.Oleoyl-estrone induced a dose-dependent loss of weight, with decreased food intake. In 14 days, and compared with controls at the end of this period, a dose of 0.78 mumol/day induced the loss of 16.4 +/- 5.5% of body weight; the difference was maximal for doses of 15 mumol/day or higher: 24.7 +/- 3.1%. Under oleoyl-estrone treatment, body protein was preserved (positive nitrogen balances) and fat stores were wasted: lowered respiratory quotient, and deficit in energy balance; a dose of 0.78 mumol/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 adipocytes. Oleoyl-estrone effects were different from those of free estrone.A lipophilic pathway for oleoyl-estrone transport by lipoproteins is postulated, allowing chemical communication between tissues. Oleoyl-estrone may be directly involved in the control of body weight.