Menopause results in a progressive decline in 17β-estradiol (E2) levels, increased adiposity, decreased insulin sensitivity, and a higher risk for type 2 diabetes. Estrogen therapies can help reverse these effects, but the mechanism(s) by which E2 modulates susceptibility to metabolic disease is not well understood. In young C57BL/6N mice, short-term ovariectomy decreased—whereas E2 therapy restored—mitochondrial respiratory function, cellular redox state (GSH/GSSG), and insulin sensitivity in skeletal muscle. E2 was detected by liquid chromatography-mass spectrometry in mitochondrial membranes and varied according to whole-body E2 status independently of ERα. Loss of E2 increased mitochondrial membrane microviscosity and H2O2emitting potential, whereas E2 administrationin vivoandin vitrorestored membrane E2 content, microviscosity, complex I and I + III activities, H2O2emitting potential, and submaximal OXPHOS responsiveness. These findings demonstrate that E2 directly modulates membrane biophysical properties and bioenergetic function in mitochondria, offering a direct mechanism by which E2 status broadly influences energy homeostasis.

中文翻译：

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17β-雌二醇直接降低线粒体膜微粘度并改善骨骼肌的生物能功能

更年期导致17β-雌二醇（E2）水平逐渐下降，肥胖增加，胰岛素敏感性降低以及2型糖尿病的较高风险。雌激素疗法可以帮助逆转这些作用，但是人们对E2调节代谢性疾病易感性的机制还不甚了解。在年轻的C57BL / 6N小鼠中，短期卵巢切除术减少，而E2治疗恢复了，线粒体呼吸功能，细胞氧化还原状态（GSH / GSSG）和骨骼肌的胰岛素敏感性。E2是通过液相色谱-质谱法检测线粒体膜中的E2，并根据全身E2的状态而变化，而与ERα无关。E2的损失增加了线粒体膜的微粘度和H2O2的释放潜力，而体内和体外施用E2可以恢复膜的E2含量，微粘度，复杂的I和I + III活性，H2O2发射潜能和OXPHOS响应能力不足。这些发现表明，E2直接调节线粒体的膜生物物理特性和生物能功能，提供了直接机制，据此E2的状态广泛影响能量稳态。