PhD, Department of Pediatrics, University of Colorado Denver, MS C225, 12700 East 19th Avenue, Aurora, Colorado 80045.
J Clin Endocrinol Metab. 2013 Oct;98(10):E1601-9. doi: 10.1210/jc.2013-1943. Epub 2013 Aug 16.
Insulin resistance and systemic oxidative stress are prominent features of pregnancies complicated by maternal obesity or gestational diabetes mellitus (GDM). The role of skeletal muscle oxidative stress or mitochondrial capacity in obese pregnant women or obese women with GDM is unknown.
We investigated whether obese pregnant women, compared with normal weight (NW) pregnant women, demonstrate decreased skeletal muscle mitochondrial enzyme activity and elevated markers of oxidative stress, and if these differences are more severe in obese women diagnosed with GDM.
We measured mitochondrial enzyme activity and markers of oxidative stress in skeletal muscle tissue from NW pregnant women (n = 10), obese pregnant women with normal glucose tolerance (NGT; n = 10), and obese pregnant women with GDM (n = 8), undergoing cesarean delivery (∼37 wk gestation).
Electron transport complex-II and manganese superoxide dismutase (MnSOD) enzyme activities were decreased in obese-NGT and obese-GDM, compared with NW women. The glutathione redox ratio (GSH:GSSG) was decreased in obese-NGT and obese-GDM, indicative of increased oxidative stress. Mitochondrial sirtuin (SIRT)3 mRNA content and enzyme activity were lower in skeletal muscle of obese-NGT and obese-GDM women. Importantly, acetylation of MnSOD, a SIRT3 target, was increased in obese-NGT and obese-GDM vs NW women and was inversely correlated with SIRT3 activity (r = -0.603), suggesting a mechanism for reduced MnSOD activity.
These data show that obese pregnant women demonstrate decreased skeletal muscle mitochondrial respiratory chain enzyme activity and decreased mitochondrial antioxidant defense. Furthermore, reduced skeletal muscle SIRT3 activity may play a role in the increased oxidative stress associated with pregnancies complicated by obesity.
胰岛素抵抗和系统性氧化应激是肥胖或妊娠糖尿病（GDM）孕妇的突出特征。肥胖孕妇或肥胖合并 GDM 孕妇骨骼肌氧化应激或线粒体功能的作用尚不清楚。
我们研究了与正常体重（NW）孕妇相比，肥胖孕妇是否表现出骨骼肌线粒体酶活性降低和氧化应激标志物升高，如果肥胖合并 GDM 的孕妇这些差异更为严重。
我们测量了行剖宫产术（约 37 周妊娠）的 NW 孕妇（n = 10）、糖耐量正常的肥胖孕妇（n = 10）和肥胖合并 GDM 孕妇（n = 8）骨骼肌组织中的线粒体酶活性和氧化应激标志物。
与 NW 妇女相比，肥胖-NGT 和肥胖-GDM 患者的电子传递复合物-II 和锰超氧化物歧化酶（MnSOD）酶活性降低。谷胱甘肽氧化还原比（GSH：GSSG）降低，表明氧化应激增加。骨骼肌中 SIRT3 mRNA 含量和酶活性在肥胖-NGT 和肥胖-GDM 妇女中降低。重要的是，MnSOD 的乙酰化（SIRT3 的一个靶标）在肥胖-NGT 和肥胖-GDM 妇女中增加，与 SIRT3 活性呈负相关（r = -0.603），表明 MnSOD 活性降低的机制。
这些数据表明，肥胖孕妇表现出骨骼肌线粒体呼吸链酶活性降低和线粒体抗氧化防御降低。此外，骨骼肌 SIRT3 活性降低可能与肥胖合并妊娠时的氧化应激增加有关。
