Department of Nutrition and Food Science, Faculty of Biology, University of Barcelona, Barcelona, Spain.
J Steroid Biochem Mol Biol. 2011 Apr;124(3-5):99-111. doi: 10.1016/j.jsbmb.2011.01.017. Epub 2011 Feb 12.
Oleoyl-estrone (OE) is a powerful anti-obesity compound that decreases food intake, decreases insulin resistance and circulating cholesterol. OE stimulates a severe loss of body fat by decreasing adipose tissue lipid synthesis and maintaining lipolysis. Therefore, the body economy loses lipid energy because energy expenditure is maintained. This study analyses the discrepancy between OE effects and the distribution of labelled OE in plasma. Estrone radioimmunoassay of organic solvent plasma extracts of rats treated with OE showed the massive presence of acyl-estrone, but saponification did not release estrone, but containing similar unknown compound. Analysis of label distribution in plasma after oral gavages of (3)H-OE showed the presence of a more hydrophilic compound than OE or any estrogen as well as (3)H(2)O, formed from (3)H-OE in the acidic stomach medium. OE was not attached to a specific transporter in plasma. Through serum HPLC analysis we found W, a labelled derivative more hydrophilic than OE or estrone. The results were confirmed using (14)C-OE. HPLC-MS/MS studies showed that plasma OE levels were one order of magnitude lower than those of W. When liver cell cytosols from rats laden with (3)H-OE were incubated with nuclei from untreated rats, the OE-derived label (i.e., Ws) was found attached to nuclear DNA. Neither estradiol nor estrone interfered with its binding. W is a fairly hydrophilic compound of low molecular weight containing the estrone nucleus, but it is not an ester because saponification or esterases do not yield estrone as OE does. It is concluded that OE acts through its conversion to W, its active form; which binds to a nuclear receptor different from that of estrogen. The estimated W serum levels are proportional to the pharmacological OE effects in vivo. We postulate W as a new type of hormone that exerts the full range of in vivo effects thus far attributed to OE. The full identification of W is anticipated to open the way for the development of new OE-like anti-obesity drugs.
油酰雌酮（OE）是一种强大的抗肥胖化合物，可减少食物摄入、降低胰岛素抵抗和循环胆固醇。OE 通过减少脂肪组织脂质合成和维持脂肪分解来刺激严重的体脂损失。因此，身体会失去脂质能量，因为能量消耗得以维持。本研究分析了 OE 作用与标记 OE 在血浆中的分布之间的差异。OE 处理大鼠的有机溶剂血浆提取物的雌酮放射免疫分析显示大量存在酰基雌酮，但皂化并未释放雌酮，而是含有类似的未知化合物。口服（3）H-OE 后标记在血浆中的分布分析显示，存在一种比 OE 或任何雌激素更亲水的化合物，以及（3）H（2）O，这是由（3）H-OE 在酸性胃介质中形成的。OE 未附着在血浆中的特定转运体上。通过血清 HPLC 分析，我们发现 W，一种比 OE 或雌酮更亲水的标记衍生物。使用（14）C-OE 对结果进行了验证。HPLC-MS/MS 研究表明，血浆 OE 水平比 W 的水平低一个数量级。当用（3）H-OE 负载的大鼠肝细胞胞浆与未处理大鼠的核孵育时，发现 OE 衍生的标记物（即 Ws）与核 DNA 结合。雌二醇或雌酮均不干扰其结合。W 是一种分子量较低的相当亲水的化合物，含有雌酮核，但它不是酯，因为皂化或酯酶不会像 OE 那样产生雌酮。因此，可以得出结论，OE 通过其转化为 W（其活性形式）起作用；其与不同于雌激素的核受体结合。估计的 W 血清水平与 OE 在体内的药理学作用成正比。我们假设 W 是一种新型激素，它发挥了迄今为止归因于 OE 的所有体内作用。W 的完全鉴定有望为开发新型 OE 样抗肥胖药物开辟道路。
