BACKGROUND Catecholamine-stimulated lipolysis is reduced with aging, which may promote adiposity and insulin resistance. Organic cation transporter 3 (OCT3), which is inhibited by estradiol (E2), mediates catecholamine transport into adipocytes for degradation, thus decreasing lipolysis. In this study, we investigated the association of OCT3 mRNA levels in subcutaneous adipose tissue (SAT) with aging and markers of insulin resistance in women. METHODS SAT biopsies were obtained from 66 women with (19) or without (47) type 2 diabetes (age 22-76 years, 20.0-40.1 kg/m2). OCT3 mRNA and protein levels were measured for group comparisons and correlation analysis. SAT was incubated with E2 and OCT3 mRNA levels were measured. Associations between OCT3 single nucleotide polymorphisms (SNPs) and diabetes-associated traits were assessed. RESULTS OCT3 mRNA and protein levels in SAT increased with aging. SAT from postmenopausal women had higher levels of OCT3 than premenopausal women, and there was a dose-dependent reduction in OCT3 mRNA levels in SAT treated with E2. OCT3 mRNA levels were negatively associated with markers of insulin resistance, and ex vivo lipolysis. OCT3 SNPs were associated with BMI, waist to hip ratio, and circulating lipids (eg, triglycerides). CONCLUSION OCT3 mRNA and protein levels in SAT increased with aging, and mRNA levels were negatively associated with markers of insulin resistance. E2 incubation downregulated OCT3 mRNA levels, which may explain lower OCT3 mRNA in premenopausal vs postmenopausal women. High OCT3 protein levels in adipose tissue may result in increased catecholamine degradation, and this can contribute to the reduction in lipolysis observed in women with aging.

中文翻译：

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随着衰老，脂肪组织中 OCT3 表达增加：对女性儿茶酚胺、脂质周转和胰岛素抵抗的影响。

背景技术儿茶酚胺刺激的脂肪分解随着年龄的增长而减少，这可能促进肥胖和胰岛素抵抗。有机阳离子转运蛋白 3 (OCT3) 受到雌二醇 (E2) 的抑制，介导儿茶酚胺转运到脂肪细胞中进行降解，从而减少脂肪分解。在这项研究中，我们调查了女性皮下脂肪组织 (SAT) 中 OCT3 mRNA 水平与衰老和胰岛素抵抗标志物的关系。方法 对 66 名患有 (19) 或不患有 (47) 2 型糖尿病的女性（年龄 22-76 岁，20.0-40.1 kg/m2）进行 SAT 活检。测量 OCT3 mRNA 和蛋白水平以进行组间比较和相关性分析。SAT 与 E2 一起孵育并测量 OCT3 mRNA 水平。评估了 OCT3 单核苷酸多态性 (SNP) 与糖尿病相关性状之间的关联。结果 SAT 中的 OCT3 mRNA 和蛋白水平随着年龄的增长而增加。绝经后女性的 SAT 的 OCT3 水平高于绝经前女性，并且用 E2 处理的 SAT 中 OCT3 mRNA 水平呈剂量依赖性降低。OCT3 mRNA 水平与胰岛素抵抗和离体脂肪分解标志物呈负相关。OCT3 SNP 与 BMI、腰臀比和循环脂质（例如甘油三酯）相关。结论 SAT中OCT3 mRNA和蛋白水平随着年龄增长而增加，且mRNA水平与胰岛素抵抗标志物呈负相关。E2 孵育下调 OCT3 mRNA 水平，这可能解释绝经前女性与绝经后女性相比 OCT3 mRNA 较低的原因。脂肪组织中的高 OCT3 蛋白水平可能会导致儿茶酚胺降解增加，这可能有助于在衰老女性中观察到的脂肪分解减少。