Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice.

Abstract

Hypoadiponectinemia has been widely observed in patients with gestational diabetes mellitus (GDM). To investigate the causal role of hypoadiponectinemia in GDM, adiponectin gene knockout (<i>Adipoq^-/-</i> ) and wild-type (WT) mice were crossed to produce pregnant mouse models with or without adiponectin deficiency. Adenoviral vector-mediated in vivo transduction was used to reconstitute adiponectin during late pregnancy. Results showed that <i>Adipoq^-/-</i> dams developed glucose intolerance and hyperlipidemia in late pregnancy. Increased fetal body weight was detected in <i>Adipoq^-/-</i> dams. Adiponectin reconstitution abolished these metabolic defects in <i>Adipoq^-/-</i> dams. Hepatic glucose and triglyceride production rates of <i>Adipoq^-/-</i> dams were significantly higher than those of WT dams. Robustly enhanced lipolysis was found in gonadal fat of <i>Adipoq^-/-</i> dams. Interestingly, similar levels of insulin-induced glucose disposal and insulin signaling in metabolically active tissues in <i>Adipoq^-/-</i> and WT dams indicated that maternal adiponectin deficiency does not reduce insulin sensitivity. However, remarkably decreased serum insulin concentrations were observed in <i>Adipoq^-/-</i> dams. Furthermore, β-cell mass, but not glucose-stimulated insulin release, in <i>Adipoq^-/-</i> dams was significantly reduced compared with WT dams. Together, these results demonstrate that adiponectin plays an important role in controlling maternal metabolic adaptation to pregnancy.