Role of estrogen on skeletal muscle mitochondrial function in ovariectomized rats: a time course study in different fiber types
Role of estrogen on skeletal muscle mitochondrial function in ovariectomized rats: a time course study in different fiber types
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DOI：
10.1152/japplphysiol.00121.2013
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发表时间：
2014-04-01
影响因子：
3.3
通讯作者：
Carvalho, D. P.
中科院分区：
文献类型：
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作者：
Cavalcanti-de-Albuquerque, J. P. A.;Salvador, I. C.;Carvalho, D. P.
绝经后妇女容易发生肥胖和胰岛素抵抗，这可能与骨骼肌线粒体功能障碍有关。在大鼠模型卵巢切除术（OVX），骨骼肌线粒体功能进行了检查，在短期和长期去势后。比目鱼肌和白色腓肠肌肌纤维的线粒体参数进行了分析。术后三周，线粒体呼吸（ATP合成）与丙酮酸、苹果酸和琥珀酸、质子漏呼吸或线粒体活性氧产生无差异。然而，3周后的OVX，比目鱼肌和白色腓肠肌的OVX动物表现出较低的使用棕榈酰肉碱和甘油磷酸盐底物，分别减少过氧化物酶体增殖物激活受体-γ共激活因子-1 α的表达。雌激素替代恢复了所有这些表型。OVX后8周，OVX动物比目鱼肌和白色腓肠肌的ATP合成低于假手术和雌激素治疗的动物;然而，当通过柠檬酸合酶活性进行标准化时，这些差异消失，表明肌肉线粒体含量较低。质子泄漏参数未观察到差异。线粒体的改变并没有损害OVX动物的跑步机运动能力。然而，在OVX动物的血液乳酸水平较高的物理测试后，表明一个补偿线粒体外ATP合成系统，但这种表型逆转雌激素替代。这些结果表明，早期线粒体功能障碍与脂质底物的使用，这可能与卵巢切除动物的超重表型的发展。
Postmenopausal women are prone to develop obesity and insulin resistance, which might be related to skeletal muscle mitochondrial dysfunction. In a rat model of ovariectomy (OVX), skeletal muscle mitochondrial function was examined at short- and long-term periods after castration. Mitochondrial parameters in the soleus and white gastrocnemius muscle fibers were analyzed. Three weeks after surgery, there were no differences in coupled mitochondrial respiration (ATP synthesis) with pyruvate, malate, and succinate; proton leak respiration; or mitochondrial reactive oxygen species production. However, after 3 wk of OVX, the soleus and white gastrocnemius muscles of the OVX animals showed a lower use of palmitoyl-carnitine and glycerol-phosphate substrates, respectively, and decreased peroxisome proliferator-activated receptor-gamma coactivator-1 alpha expression. Estrogen replacement reverted all of these phenotypes. Eight weeks after OVX, ATP synthesis was lower in the soleus and white gastrocnemius muscles of the OVX animals than in the sham-operated and estrogen-treated animals; however, when normalized by citrate synthase activity, these differences disappeared, indicating a lower muscle mitochondria content. No differences were observed in the proton leak parameter. Mitochondrial alterations did not impair the treadmill exercise capacity of the OVX animals. However, blood lactate levels in the OVX animals were higher after the physical test, indicating a compensatory extramitochondrial ATP synthesis system, but this phenotype was reverted by estrogen replacement. These results suggest early mitochondrial dysfunction related to lipid substrate use, which could be associated with the development of the overweight phenotype of ovariectomized animals.