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.
Bibliographical noteFunding Information:
This publication was supported by grant number R01 MH107508R01 (ES) from the National Institute of Mental Health at the National Institutes of Health (NIH), the Murdock Charitable Trust, Murdock College Research Program for Life Science, grant number 2011273:HVP (ES), Oregon Clinical and Translational Research Institute grant number UL1TR000128 (ES) from the National Center for Advancing Translational Sciences at the NIH. Research reported in this publication was also supported by NIH under award number TL1TR002371 (HG) from the National Center for Advancing Translational Sciences and from grant number P51 OD011092 for the operation of ONPRC and support of the Endocrine Technologies Support Core (ETSC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Trust.
- Macrophage-derived chemokine (MDC)