ISSN:
1436-6215
Keywords:
Key words Obesity – oleoyl-estrone – leptin – Zucker fa/fa rat – white adipose tissue
Source:
Springer Online Journal Archives 1860-2000
Topics:
Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
,
Medicine
Notes:
Summary 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. Aim of the study: 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. Conclusion: The presence of an intact 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s003940050050
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