Mothers with obesity and gestational diabetes did not induce brain pathologies or premature brain aging in their adolescent and early adult offspring in rats

Abstract

This study investigated the effect of a medium high-fat diet (HFD)-induced maternal obesity and gestational diabetes mellitus (GDM) on rat offspring to verify the hypothesis that maternal obesity and GDM cause brain pathologies and premature brain aging in the prefrontal cortex and hippocampus of the adolescent and early adult offspring. Maternal obesity and GDM were generated by a medium HFD and HFD combined with streptozotocin, respectively. Metabolic parameters were used to confirm the successful model in mothers. Systemic alterations and brain pathology were investigated in their adolescent and early adult offspring. During pregnancy, HFD-fed rats exhibited obesity, while GDM rats had hyperglycemia with insulin resistance. Offspring from high-fat diet dams (OHFD) had higher body weight when compared with offspring from normal diet dams (OND), while offspring from gestational diabetes mellitus dams (OGDM) had lower body weight than OHFD but comparable with OND. No significant alterations were found in glucose tolerance, systemic oxidative stress, and inflammation in the offspring. Additionally, neither adolescent nor early adult rats OHFD or OGDM developed brain pathologies or premature aging with no difference in oxidative stress, inflammation, mitochondrial dynamics, mitophagy, blood–brain barrier, synaptic plasticity, apoptosis, and aging markers among the offspring groups. Our results indicated that maternal obesity and GDM did not cause brain pathologies or premature brain aging at the adolescent and early adult stages of offspring in rats. Our study highlights the importance of maintaining a healthy diet in the offspring of obese and GDM mothers to keep healthy later in their lives.