Grup de Metabolisme Energètic i Nutrició (GMEIN), Departament de Biologia Fonamental i Ciències de la Salut, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Baleares, Ctra. Valldemossa, km 7.5, E-07122, Palma, Balearic Islands, Spain.
Grup de Metabolisme Energètic i Nutrició (GMEIN), Departament de Biologia Fonamental i Ciències de la Salut, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Baleares, Ctra. Valldemossa, km 7.5, E-07122, Palma, Balearic Islands, Spain; Institut d'Investigació Sanitària de les Illes Baleares (IdISBa), Hospital Universitari Son Espases, E-07120, Palma, Balearic Islands, Spain.
Free Radic Biol Med. 2024 Nov 1;224:574-587. doi: 10.1016/j.freeradbiomed.2024.09.001. Epub 2024 Sep 4.
Estrogens have a well-known protective role in the development of the metabolic syndrome. Nevertheless, recent epidemiological data question the cardioprotective effect of estrogens in obese and diabetic women. In this context, white adipose tissue (WAT) becomes dysfunctional, which has an impact on the cardiovascular system. The aim of the study was to elucidate the role of 17β-estradiol (E2) in the interplay between adipose tissue and endothelial function in an animal model of diabesity. We used ZDF (fa/fa) female rats subjected to ovariectomy (OVA), OVA + E2 or sham operated, as well as non-obese non-diabetic ZDF (fa/+) rats. Endothelial function and vascular remodeling markers were assessed in the aorta, while mitochondrial function, oxidative stress, and adiponectin production were analyzed in gonadal WAT. Conditioned media from gonadal WAT explants were used to assess the effects of WAT secretome on HUVEC. Additionally, the adiponectin receptor agonist AdipoRON and E2 were utilized to examine potential interactions. Ovariectomy ameliorated the WAT dysfunction associated to the obese and diabetic state and promoted adiponectin secretion, effects that were linked to a reduction of endothelial dysfunction and inflammatory markers in the aorta of OVA rats and in HUVEC treated with OVA-conditioned media. Our findings provide evidence supporting the idea that in the context of obesity and diabetes, ovariectomy improves WAT secretome and positively impacts endothelial function, suggesting a detrimental role for E2. Additionally, our results point to adiponectin as the primary driver of the effects exerted by ovariectomy on the adipovascular axis.
雌激素在代谢综合征的发展中具有众所周知的保护作用。然而，最近的流行病学数据对肥胖和糖尿病女性中雌激素的心脏保护作用提出了质疑。在这种情况下，白色脂肪组织（WAT）变得功能失调，这对心血管系统有影响。本研究旨在阐明 17β-雌二醇（E2）在肥胖糖尿病动物模型中脂肪组织和内皮功能相互作用中的作用。我们使用 ZDF（fa/fa）雌性大鼠进行卵巢切除术（OVA）、OVA+E2 或假手术，以及非肥胖非糖尿病的 ZDF（fa/+）大鼠。评估了主动脉内皮功能和血管重塑标志物，同时分析了性腺 WAT 中的线粒体功能、氧化应激和脂联素产生。使用性腺 WAT 外植体的条件培养基来评估 WAT 分泌组对 HUVEC 的影响。此外，还使用了脂联素受体激动剂 AdipoRON 和 E2 来研究潜在的相互作用。卵巢切除术改善了与肥胖和糖尿病状态相关的 WAT 功能障碍，并促进了脂联素的分泌，这些作用与 OVA 大鼠主动脉内皮功能障碍和炎症标志物的减少以及接受 OVA 条件培养基处理的 HUVEC 相关。我们的研究结果提供了证据支持这样一种观点，即在肥胖和糖尿病的情况下，卵巢切除术改善了 WAT 分泌组，并对内皮功能产生积极影响，这表明 E2 发挥了有害作用。此外，我们的结果表明脂联素是卵巢切除术对脂肪血管轴的影响的主要驱动因素。
