Abstract
Obesity induces a low-grade inflammatory state and has been associated with behavioral and cognitive alterations. Importantly, maternal environmental insults can adversely impact subsequent offspring behavior and have been linked with neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (AHDH). It is unknown if maternal obesity significantly alters offspring sociability, a key ASD feature, and if altering maternal diet will provide an efficacious intervention paradigm for behavioral deficits. Here we investigated the impact of maternal high fat diet (HFD) and maternal dietary intervention during lactation on offspring behavior and brain inflammation in mice. We found that maternal HFD increased anxiety and decreased sociability in female offspring. Additionally, female offspring from HFD-fed dams also exhibited increased brain IL-1β and TNFΑ and microglial activation. Importantly, maternal dietary intervention during lactation was sufficient to alleviate social deficits and brain inflammation. Maternal obesity during gestation alone was sufficient to increase hyperactivity in male offspring, a phenotype that was not ameliorated by dietary intervention. These data suggest that maternal HFD acts as a prenatal/perinatal insult that significantly impacts offspring behavior and inflammation and that dietary intervention during lactation may be an easily translatable, efficacious intervention to offset some of these manifestations.
Highlights
Maternal obesity is a pervasive health issue, with over 30% of child-bearing age women in the United States being categorized as obese [1]
Maternal high fat diet increases weight in both dams and offspring To examine the contribution of maternal HFD during gestation and/or lactation on subsequent offspring, female C57BL/6 J mice were placed on either a HFD (60% calories from fat) or control diet CD (10% calories from fat)
The average days between initial mating and pup birth was similar for both CD and HFD-fed dams
Summary
Maternal obesity is a pervasive health issue, with over 30% of child-bearing age women in the United States being categorized as obese [1]. Adverse symptoms such as gestational diabetes, pre-term birth, and birth injury are associated with maternal obesity [2,3,4]. ADHD symptoms in children have been associated with pre-pregnancy adiposity [22,23,24] and animal models of maternal high fat diet (HFD) revealed increased offspring activity [25]. Maternal obesity or infection has been linked to increased autism risk in children [28,29,30]. While rodent modeling of maternal infection results in offspring displaying features of ASD [31,32], it is unknown whether maternal obesity alone induces any ASD-like behaviors in subsequent offspring
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