Neurobehavioral consequences of perinatal high-fat diet exposure: Toward understanding and intervention

It is clear that an adverse perinatal environment can prime risk for neuropsychiatric disease. Maternal obesity and globalization of the Western-style diet is a public health concern and maternal overnutrition has emerged as a prevalent environment of perinatal adversity. Indeed, epidemiological studies associate maternal overnutrition with increased neuropsychiatric risk to offspring. However, underlying mechanisms remain unclear, as do potential routes for intervention. In this report, we used two animal models of maternal overnutrition by high-fat diet (HFD) to investigate neurobehavioral outcomes in offspring and mechanistic correlates. In the first series of studies, we demonstrate that perinatal HFD exposure in rodents resulted in impaired cognitive performance in adult offspring that is associated with decreased gene expression of the NMDA glutamate receptor subunit GluN2B (Grin2b) in the hippocampus. Voluntary maternal exercise during gestation normalized both cognitive performance and hippocampal Grin2b expression in adult offspring exposed to perinatal HFD. HFD also resulted in adverse changes to systemic metabolic and inflammatory markers in dams, which were partially mitigated by maternal exercise. In the second series of studies, we use a non-human primate model of perinatal high-fat Western-style diet (WSD) to investigate neurobehavioral outcomes in juvenile offspring. Perinatal WSD resulted in increased restricted repetitive behaviors and decreased pro-social behavior in juvenile offspring exposed to social novelty. Offspring behavioral impairments were associated with an altered maternal systemic environment characterized by metabolic dysregulation and changes in circulating inflammatory markers. We further found that levels of perinatal systemic metabolic and inflammatory markers in dams correlated with degree of behavioral impairment in offspring. Taken together, this report adds to the growing body of literature associating maternal overnutrition with neurobehavioral impairments in offspring and begins to provide mechanistic underpinnings, further elucidating the role of the maternal systemic environment in linking perinatal HFD exposure and compromised neurobehavioral programming. Moreover, we show that maternal exercise during gestation is a promising, clinically relevant intervention to mitigate the neurobehavioral consequences of perinatal HFD. Further investigation into the mechanistic relationships suggested here and gestational exercise exposure as an intervention may ultimately provide insights to address the growing prevalence of neurodevelopmental and neuropsychiatric illnesses