Abstract

Perinatal exposure to maternal obesity and high-fat diet (HFD) consumption not only poses metabolic risks to offspring but also impacts brain development and mental health. Using a non-human primate model, we observed a persistent increase in anxiety in juvenile offspring exposed to a maternal HFD. Postweaning HFD consumption also increased anxiety and independently increased stereotypic behaviors. These behavioral changes were associated with modified cortisol stress response and impairments in the development of the central serotonin synthesis, with altered tryptophan hydroxylase-2 mRNA expression in the dorsal and median raphe. Postweaning HFD consumption decreased serotonergic immunoreactivity in area 10 of the prefrontal cortex. These results suggest that perinatal exposure to HFD consumption programs development of the brain and endocrine system, leading to behavioral impairments associated with mental health and neurodevelopmental disorders. Also, an early nutritional intervention (consumption of the control diet at weaning) was not sufficient to ameliorate many of the behavioral changes, such as increased anxiety, that were induced by maternal HFD consumption. Given the level of dietary fat consumption and maternal obesity in developed nations these findings have important implications for the mental health of future generations.

Highlights

  • Developed nations have experienced a surge in the prevalence of both maternal obesity and pediatric neurodevelopmental disorders

  • Maternal obesity is associated with childhood affective problems, such as increased risk of fear, sadness, and internalizing behavior [8, 12], and is correlated with low or high birth weight which are linked to anxiety and depression during adolescence [13]

  • ANCOVA results controlling for juvenile weight revealed that the amount of time spent performing anxiety behaviors increased with maternal high-fat diet (HFD) exposure (F1,65 = 4.498, p = 0.038, Figure 1B)

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Summary

Introduction

Developed nations have experienced a surge in the prevalence of both maternal obesity and pediatric neurodevelopmental disorders. Maternal obesity is associated with childhood affective problems, such as increased risk of fear, sadness, and internalizing behavior [8, 12], and is correlated with low or high birth weight which are linked to anxiety and depression during adolescence [13]. Both non-human primate (NHP) and rodent studies demonstrate that chronic maternal HFD consumption produces long-term alterations in offspring’s anxiety-related behaviors [6, 14]

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