Leptin enhances the synthesis of oleoyl-estrone from estrone in white adipose tissue.
BACKGROUND
Oleoyl-estrone elicits powerful slimming effects on lean and obese rats, sparing protein, lowering appetite and maintaining energy expenditure. Leptin synthesis is markedly reduced by oleoyl-estrone. However, this effect is not observed in the obese Zucker fa/fa rats; these rats do not fully respond to leptin but they lose fat under oleoyl-estrone treatment.


OBJECTIVE
To determine the role of leptin in the conversion of estrone to fatty-acyl estrone in white adipose tissue both in vivo in Zucker lean and obese rats, and in vitro.


METHODS
Two series of experiments were performed: a) Growth and differentiation of 3T3L1 preadipocytes into adipocytes followed by incubation with tritium-labeled estrone in the medium in the presence/absence of 1 nM leptin, and estimation of the incorporation of label into estrone and estrone ester fractions of cell extracts. b) Zucker lean (Fa/?) [ZL] and obese (fa/fa) [ZO] rats were injected i.v. with carrier-free oleoyl-estrone in chylomicra-sized liposomes, then euthanized after 10 min. Free and esterified estrone were measured in blood, liver, muscle, skin, white adipose tissue (WAT), and brown adipose tissue (BAT).


RESULTS
In the first study, in a 72-h incubation, adipocytes took up 20-27% of the medium estrone. In the leptin(-) controls, 47% of the label in the cell fraction was in the form of estrone esters and 45% as free estrone; in the leptin(+) cells, 71% of the label was in the estrone ester fraction and 24% was free estrone. In the second study, a large part of the injected tritium-label remained in the ZO blood, with only a small part remaining in ZL. In ZL 39% of the label was found in the tissues in the form of free estrone, and in ZO only 22%; in both cases about half of it was in WAT. Plasma free estrone levels were 0.3 +/- 0.1 nM in ZL and 0.5 +/- 0.3 nM in ZO, and esterified estrone was 242 +/- 99 nM for ZL and 201 +/- 29 nM for ZO. Plasma leptin levels were 1.73 +/- 0.16 ng/ml in ZL and 61.0 +/- 1.4 ng/ml in ZO.


CONCLUSIONS
The presence of an infact leptin pathway is critical for the uptake and synthesis of estrone esters as well as for the plasma acyl-estrone turnover. The presented results show a direct relationship between oleoyl-estrone and leptin in the WAT. A fully functional leptin pathway is needed for the synthesis of acyl-estrone and the removal of free estrone from the bloodstream, as well as for the disposal of excess circulating oleoyl-estrone. This has a direct bearing on human and animal obesity, since estrone induces increases in fat deposition.
Esteve
M
M
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Spain.
Virgili
J
J
Aguilar
H
H
Balada
F
F
Fernández-López
J A
JA
Remesar
X
X
Alemany
M
M
D016475:3T3 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004970:Estrone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D005260:Female; D020738:Leptin; D008099:Liver / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000378:metabolism; D009765:Obesity; D009829:Oleic Acids / Q000096:biosynthesis* / Q000097:blood; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011924:Rats, Zucker; D012016:Reference Values; D012588:Scintillation Counting; D012867:Skin / Q000378:metabolism
D020738:Leptin; D009829:Oleic Acids; D011506:Proteins; D004970:Estrone; C108709:oleoyl-estrone