TitleSkeletal muscle MnSOD, mitochondrial complex II, and SIRT3 enzyme activities are decreased in maternal obesity during human pregnancy and gestational diabetes mellitus.
Publication TypeJournal Article
Year of Publication2013
AuthorsBoyle, KE, Newsom, SA, Janssen, RC, Lappas, M, Friedman, JE
JournalJ Clin Endocrinol Metab
Volume98
Issue10
PaginationE1601-9
Date Published10/2013
ISSN1945-7197
KeywordsDiabetes, Gestational, Electron Transport Complex II, Female, Glutathione, Humans, Mitochondria, Muscle, Skeletal, Obesity, Oxidative Stress, Pregnancy, Sirtuin 3, Superoxide Dismutase
Abstract
 

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 (∼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.

DOI10.1210/jc.2013-1943
Alternate JournalJ. Clin. Endocrinol. Metab.
PubMed ID23956348
PubMed Central IDPMC3790616
Grant ListT32 DK007658 / DK / NIDDK NIH HHS / United States
R01 DK062155 / DK / NIDDK NIH HHS / United States
P30 DK048520 / DK / NIDDK NIH HHS / United States
DK 5R01DK062155 / DK / NIDDK NIH HHS / United States
F32 DK095509 / DK / NIDDK NIH HHS / United States
F32 DK 089743 / DK / NIDDK NIH HHS / United States
K12 HD057022 / HD / NICHD NIH HHS / United States
F32 DK089743 / DK / NIDDK NIH HHS / United States