Normalizing adiponectin levels in obese pregnant mice prevents adverse metabolic outcomes in offspring

Abstract

Infants of obese mothers have an increased risk of developing obesity, insulin resistance, and type 2 diabetes. The underlying mechanisms remain elusive, and no effective interventions to limit the transmission of metabolic disease from the obese mother to her infant are currently available. Obese pregnant women have decreased circulating levels of adiponectin, which is associated with increased placental nutrient transport and fetal overgrowth. We have reported that normalization of adiponectin levels during late gestation reversed placental dysfunction and fetal overgrowth in a mouse model of maternal obesity in pregnancy. In the current study, we hypothesized that adiponectin supplementation during pregnancy in obesemice attenuates the adversemetabolic outcomes in adult offspring. Adult male offspring of obese mice developed obesity, fatty liver, and insulin resistance, with adult female offspring of obesemicehaving a lesspronouncedmetabolic phenotype.Thesemetabolic abnormalities in offspring born to obese mice were largely prevented by normalization of maternal adiponectin levels in late pregnancy.We provide evidence that lowcirculatingmaternal adiponectin is a criticalmechanistic link between maternal obesity and the development of metabolic disease in offspring. Strategies aimed at improving maternal adiponectin levelsmayprevent long-termmetabolic dysfunction inoffspring of obesemothers.