Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates.

Jacqueline R Thompson,Tyler A Dean,Hanna C Gustafsson,Madison Decapo,Damien A Fair,Paul Kievit,Elinor L Sullivan,Jennifer L Bagley,Diana L Takahashi

doi:10.3389/fendo.2018.00161

Abstract

Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes) increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD), metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC) exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation.

Highlights

As trends toward global urbanization rise, a Western-style diet (WSD) is becoming increasingly common worldwide
We posited that maternal WSD consumption alone would alter the maternal inflammatory profile to which offspring were exposed during prenatal development and independently impact offspring behavioral response
In our examination of maternal inflammation during pregnancy, macrophage-derived chemokine (MDC) was of stand-alone importance for predicting offspring behavioral outcome

Summary

Introduction

As trends toward global urbanization rise, a Western-style diet (WSD) is becoming increasingly common worldwide. Increased consumption of a WSD is altering public health concerns, as the risk of nutrient deficiency and infectious diseases is falling while the prevalence of cardiometabolic diseases grows [1]. It is well established that maternal diet and metabolic state during pregnancy alter future risk of metabolic disease in offspring [5]. Gestational factors such as increased maternal weight gain, obesity, and impaired glucose metabolism can likewise impact offspring neurodevelopment, increasing the risk of neuropsychiatric disorders [6,7,8]. Perinatal nutrition is an important determinant of children’s neural outcome, and exposure to aspects of a WSD during the perinatal period increases risk of neuropsychiatric disorders such as autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and schizophrenia [9,10,11]

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