Exposure to maternal high-fat diet induces extensive changes in the brain of adult offspring

Darren J Fernandes,Mark R Palmert,Anna R Roy,Lily R Qiu,Brian J Nieman,Jason P Lerch,Yohan Yee,Shoshana Spring

doi:10.1038/s41398-021-01274-1

Abstract

Maternal environmental exposures, such as high-fat diets, diabetes and obesity, can induce long-term effects in offspring. These effects include increased risk of neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), depression and anxiety. The mechanisms underlying these late-life neurologic effects are unknown. In this article, we measured changes in the offspring brain and determined which brain regions are sensitive to maternal metabolic milieu and therefore may mediate NDD risk. We showed that mice exposed to a maternal high-fat diet display extensive brain changes in adulthood despite being switched to a low-fat diet at weaning. Brain regions impacted by early-life diet include the extended amygdalar system, which plays an important role in reward-seeking behaviour. Genes preferentially expressed in these regions have functions related to feeding behaviour, while also being implicated in human NDDs, such as autism. Our data demonstrated that exposure to maternal high-fat diet in early-life leads to brain alterations that persist into adulthood, even after dietary modifications.

Highlights

The prevalence of obesity is increasing among women of reproductive age[1,2]
Evidence has shown that the perinatal exposure to maternal obesity and associated metabolic abnormalities increases the risk of neurodevelopmental disorders (NDDs) in offspring, including attention deficit hyperactivity disorder, autism spectrum disorders, anxiety, depression, schizophrenia and eating disorders[9,10,11,12]
We demonstrated that high-fat exposure in early-life caused structural changes in offspring brains that persisted into adulthood, even after the high-fat diet was removed and metabolic abnormalities attenuated

Summary

Introduction

The prevalence of obesity is increasing among women of reproductive age[1,2]. Overweight or obese mothers may predispose their children to adverse health outcomes – such as diabetes, obesity and coronary heart disease[3,4,5]. Evidence has shown that the perinatal exposure to maternal obesity and associated metabolic abnormalities increases the risk of neurodevelopmental disorders (NDDs) in offspring, including attention deficit hyperactivity disorder, autism spectrum disorders, anxiety, depression, schizophrenia and eating disorders[9,10,11,12]. Mouse models provide an important opportunity to explore this link; the effects of typical human “Western” diets (which consists of 30–40% of calories from fats), including characteristic metabolic abnormalities, have been successfully recapitulated in mice fed diets consisting of 40–60% fat[13,14,15]. Offspring of rodents fed high-fat diet exhibit a wide range of behavioural changes consistent with NDDs16,17. Rodents exposed to high-fat diet before weaning displayed increased susceptibility to depression-like behaviours[18], increased anxiety[19] and impaired spatial learning[20]

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