Prenatal Exposure to Maternal Obesity Alters Anxiety and Stress Coping Behaviors in Aged Mice.

Background: There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders.

Methods: We used a mouse model of maternal diet-induced obesity to investigate whether maternal obesity affects the response to adult chronic stress exposure in young adult (3-month-old) and aged adult (12-month-old) offspring.

Results: Long-lasting, delayed impairments to anxiety-like behaviors and stress coping strategies resulted on account of prenatal exposure to maternal obesity. Although maternal obesity did not change the offspring's behavioral response to chronic stress per se, we demonstrate that the behavioral outcomes induced by prenatal exposure to maternal obesity parallel the deleterious effects of adult chronic stress exposure in aged male mice. We found that the glucocorticoid receptor (GR, Nr3c1) is upregulated in various hypothalamic nuclei on account of maternal obesity. In addition, gene expression of a known regulator of the GR, FKBP51, is increased specifically within the paraventricular nucleus.

Conclusions: These findings indicate that maternal obesity parallels the deleterious effects of adult chronic stress exposure, and furthermore identifies GR/FKBP51 signaling as a novel candidate pathway regulated by maternal obesity.