Data from: Estradiol-mediated improvements in adipose tissue insulin sensitivity are related to the balance of adipose tissue estrogen receptor α and β in postmenopausal women

We recently demonstrated that short-term estradiol (E2) treatment improved insulin-mediated suppression of lipolysis in postmenopausal women, but to a greater extent in those who were late compared to early postmenopausal. In this follow-up study we tested whether subcutaneous adipose tissue (SAT) expression of estrogen receptors (ER) α and β differs between early and late postmenopausal women. We further tested whether the balance of ERα to ERβ in SAT determined the effect of E2 on SAT insulin sensitivity. The present study included 35 women who were ≤6 years past menopause (EPM; n = 16) or ≥10 years past menopause (LPM; n = 19). Fasted SAT samples were taken following 1-week transdermal E2 treatment or placebo (PL) in a random cross-over design. Samples were analyzed for nuclear/cytosolic protein content and mRNA expression using Western blot and qPCR, respectively. While ESR1 increased slightly (~1.4-fold) following E2 treatment in both groups, ERα and ERβ protein expression did not differ between groups at baseline or in response to E2. However, the balance of ERα/ERβ protein in the SAT nuclear fraction increased 10% in EPM compared to a 25% decrease in LPM women (group x treatment interaction, p<0.05). A greater proportion of ERα/ERβ protein in the nuclear fraction of SAT at baseline (placebo day) was associated with greater reduction in SAT insulin resistance (i.e., better suppression of lipolysis, EC50) in response to E2 (r = -0.431, p<0.05). In conclusion, there do not appear to be differences in the proportion of adipose tissue ERα/ERβ protein in late, compared to early, postmenopausal women. However, the balance of ERα/ERβ may be important for E2-mediated improvement in adipose tissue insulin sensitivity.我们此前的研究表明，短期雌二醇（estradiol, E2）治疗可改善绝经后女性的胰岛素介导脂解抑制效应，且在绝经晚期女性中的改善效果优于绝经早期女性。本随访研究旨在探究绝经早期与晚期女性皮下脂肪组织（subcutaneous adipose tissue, SAT）中雌激素受体（estrogen receptors, ER）α和β的表达水平是否存在差异，并进一步验证SAT中ERα与ERβ的表达平衡是否会影响E2对SAT胰岛素敏感性的调控作用。本研究共纳入35名女性，其中绝经时长≤6年者为绝经早期组（early postmenopausal, EPM; n = 16），绝经时长≥10年者为绝经晚期组（late postmenopausal, LPM; n = 19）。所有受试者采用随机交叉设计，先后接受为期1周的经皮E2治疗或安慰剂（placebo, PL）干预，干预结束后采集空腹SAT样本。分别采用蛋白质印迹法（Western blot）与实时定量聚合酶链式反应（qPCR）检测样本的核/胞浆蛋白含量及mRNA表达水平。两组受试者的ESR1（ERα编码基因）表达在E2治疗后均小幅上调（约1.4倍），但两组基线及E2干预后的ERα、ERβ蛋白表达水平均无显著差异。然而，与绝经晚期组中ERα/ERβ蛋白比值下降25%相比，绝经早期组的SAT核组分中ERα/ERβ蛋白比值升高了10%（组×处理交互作用，p<0.05）。基线（安慰剂干预日）时SAT核组分中ERα/ERβ蛋白比值更高的受试者，其接受E2治疗后SAT胰岛素抵抗的改善程度更显著（即脂解抑制效果更强，半数有效浓度EC50更低），二者呈显著负相关（r = -0.431, p<0.05）。综上，绝经晚期与早期女性的脂肪组织ERα/ERβ蛋白比例并无显著差异，但ERα与ERβ的表达平衡可能在E2介导的脂肪组织胰岛素敏感性改善中发挥重要作用。