Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring

Background: Acute elevations in endogenous corticosterone (CORT) with psychosocial stress or exogenous administration potentiate inflammatory gene expression. Maternal obesity as a result of high-fat diet (HFD) consumption has been linked to higher basal levels of neuroinflammation, including increased expression of pro-inflammatory genes in the amygdala. These findings suggest that exposure to maternal HFD may elicit pro-inflammatory responses in the presence of an immune stressor such as lipopolysaccharide (LPS), a component of gram-negative bacteria, as well as acute elevated CORT. Methods: Rat offspring were exposed to maternal HFD or control diet (CHD) throughout pre and postnatal development until weaning, when all offspring were provided CHD until adulthood. In adulthood, offspring were challenged with administration of exogenous CORT, to simulate an acute physiological stress, LPS, to induce an immune stress, or both. qPCR was used to measure transcript abundance of CORT receptors and downstream inflammatory genes in the amygdala, hippocampus and prefrontal cortex, brain regions that mediate neuroendocrine and behavioral responses to stress. Results: HFD female offspring exhibited elevations in anti-inflammatory transcripts, whereas HFD male offspring responded with greater pro-inflammatory gene expression to simultaneous CORT and LPS administration. Conclusions: These findings suggest that exposure to maternal HFD leads to sex-specific alterations that may alter inflammatory responses in the brain, possibly as an adaptive response to basal inflammation.