Skeletal Muscle MnSOD, Mitochondrial Complex II, and SIRT3 Enzyme Activities Are Decreased in Maternal Obesity During Human Pregnancy and Gestational Diabetes Mellitus

Context: 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. Objective: 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. Design: 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 (similar to 37 wk gestation). Results: 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. Conclusions: 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.