Perinatal high fat diet alters glucocorticoid signaling and anxiety behavior in adulthood.

Maternal obesity carries significant health risks for offspring that manifest later in life, including metabolic syndrome, cardiovascular disease and affective disorders. Programming of the hypothalamic-pituitary-adrenal (HPA) axis during development mediates both metabolic homeostasis and the response to psychosocial stress in offspring. A diet high in fat alters maternal systemic corticosterone levels, but effects in offspring on limbic brain areas regulating the HPA axis and anxiety behavior are poorly understood. In addition to their role in the response to psychosocial stress, corticosteroid receptors form part of the glucocorticoid signaling pathway comprising downstream inflammatory processes. Increased systemic inflammation is a hallmark of high-fat diet exposure, though altered expression of these genes in limbic brain areas has not been examined. We studied the influence of high-fat diet exposure during pre-weaning development in rats on gene expression in the amygdala and hippocampus by quantitative real-time polymerase chain reaction (PCR), anxiety behavior in the Open field, elevated plus maze and light-dark transition tasks, and corticosterone levels in response to stress by radioimmunoassay. As adults, offspring exposed to perinatal high-fat diet show increased expression of corticosterone receptors in the amygdala and altered pro-inflammatory and anti-inflammatory expression in the hippocampus and amygdala in genes known to be regulated by the glucocorticoid receptor. These changes were associated with increased anxiety behavior, decreased basal corticosterone levels and a slower return to baseline levels following a stress challenge. The data indicate that the dietary environment during development programs glucocorticoid signaling pathways in limbic areas relevant for the regulation of HPA function and anxiety behavior.