Cavalcanti-de-Albuquerque J P A, Salvador I C, Martins Eduarda Lopes, Jardim-Messeder D, Werneck-de-Castro J P S, Galina A, Carvalho D P
Laboratório de Fisiologia Endócrina Doris Rosenthal, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;
J Appl Physiol (1985). 2014 Apr 1;116(7):779-89. doi: 10.1152/japplphysiol.00121.2013. Epub 2014 Jan 23.
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-γ coactivator-1α 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.
绝经后女性容易出现肥胖和胰岛素抵抗，这可能与骨骼肌线粒体功能障碍有关。在卵巢切除（OVX）大鼠模型中，研究了去势后短期和长期骨骼肌线粒体功能。分析了比目鱼肌和白色腓肠肌纤维中的线粒体参数。手术后三周，丙酮酸、苹果酸和琥珀酸的偶联线粒体呼吸（ATP合成）、质子泄漏呼吸或线粒体活性氧生成方面没有差异。然而，OVX术后3周，OVX动物的比目鱼肌和白色腓肠肌分别显示出对棕榈酰肉碱和甘油磷酸底物的利用率较低，以及过氧化物酶体增殖物激活受体γ共激活因子-1α表达降低。雌激素替代可逆转所有这些表型。OVX术后8周，OVX动物比目鱼肌和白色腓肠肌中的ATP合成低于假手术和雌激素处理的动物；然而，通过柠檬酸合酶活性进行标准化后，这些差异消失，表明肌肉线粒体含量较低。在质子泄漏参数方面未观察到差异。线粒体改变并未损害OVX动物的跑步机运动能力。然而，体育测试后OVX动物的血乳酸水平较高，表明存在补偿性线粒体外ATP合成系统，但这种表型可通过雌激素替代逆转。这些结果表明与脂质底物利用相关的早期线粒体功能障碍，这可能与去卵巢动物超重表型的发展有关。
