Normalization of maternal adiponectin in obese pregnant mice prevents programming of impaired glucose metabolism in adult offspring

Infants born to obese mothers have a greater risk for childhood obesity and insulin resistance. However, the underlying biological mechanism remains elusive, which constitutes a significant roadblock for developing specific prevention strategies. Maternal adiponectin levels are lower in obese pregnant women, which is linked with increased placental nutrient transport and fetal overgrowth. We have previously reported that adiponectin supplementation to obese dams during the last four days of pregnancy prevented the development of obesity, glucose intolerance, muscle insulin resistance, and fatty liver in three months old offspring. In the present study, we tested the hypothesis that 6-9-month-old offspring of obese dams show glucose intolerance associated with muscle insulin resistance and mitochondrial dysfunction and that normalization of maternal adiponectin in obese pregnant mice prevents the development of this phenotype in the offspring. Male and female offspring of obese mice exhibited in vivo glucose intolerance and insulin resistance at 6 and 9 months of age. In gastrocnemius muscles ex vivo, male and female offspring of obese dams showed reduced phosphorylation of insulin receptor substrate 1(Tyr-608), Akt(Thr-308), and decreased Glut4 plasma membrane translocation upon insulin stimulation. These metabolic abnormalities in offspring born to obese mice were largely prevented by normalization of maternal adiponectin levels in late pregnancy. We provide evidence that low circulating maternal adiponectin is a critical mechanistic link between maternal obesity and the development of metabolic disease in offspring. Strategies aimed at improving maternal adiponectin levels may prevent long-term metabolic dysfunction in offspring of obese mothers.

Automated summary

Infants born to obese mothers have a higher risk of childhood obesity and insulin resistance. Lower levels of maternal adiponectin, a hormone associated with placental nutrient transport and fetal overgrowth, contribute to these risks. Previous research showed that supplementing adiponectin in obese mice during pregnancy prevented obesity and metabolic dysfunction in their offspring. This study further demonstrates the importance of maternal adiponectin levels in the development of metabolic diseases in offspring and suggests that improving these levels could prevent long-term metabolic dysfunction in children of obese mothers.