Maternal gestational
obesity is associated with elevated risks for
neurodevelopmental disorder, including
autism spectrum disorder. However, the mechanisms by which maternal adiposity influences fetal developmental programming remain to be elucidated. We aimed to understand the impact of
maternal obesity on the metabolism of both pregnant mothers and their offspring, as well as on metabolic, brain, and behavioral development of offspring by utilizing metabolomics,
protein, and behavioral assays in a non-human primate model. We found that
maternal obesity was associated with elevated
inflammation and significant alterations in metabolites of energy metabolism and one-
carbon metabolism in maternal plasma and urine, as well as in the placenta. Infants that were born to obese mothers were significantly larger at birth compared to those that were born to lean mothers. Additionally, they exhibited significantly reduced novelty preference and significant alterations in their emotional response to stress situations. These changes coincided with differences in the phosphorylation of
enzymes in the brain mTOR signaling pathway between infants that were born to obese and lean mothers and correlated with the concentration of maternal plasma
betaine during pregnancy. In summary, gestational
obesity significantly impacted the infant systemic and brain metabolome and adaptive behaviors.