Maternal high-fat diet induces sex-specific effects on inflammatory responses to corticosterone and lipopolysaccharide challenge in adult rat offspring

Acute elevations in endogenous CORT caused by stress or exogenous administration potentiate inflammatory gene expression. Maternal obesity through high-fat diets (HFD) has been linked to higher basal levels of neuroinflammation, including increased expression of pro-inflammatory genes such as NFκB and interleukin-6 in the amygdala. These findings suggest that adult rats exposed to maternal HFD may elicit pro-inflammatory responses in the presence of an immune stressor and elevated CORT. To investigate, adult rat offspring exposed to maternal control fat house-chow diet (CFD) or HFD were administered exogenous CORT and lipopolysaccharide (LPS), a component of gram-negative bacteria. Transcript abundance of CORT receptors and downstream inflammatory genes were measured in the amygdala, hippocampus and prefrontal cortex, brain regions that mediate neuroendocrine and behavioural responses to stress. We found sex-specific responses, where HFD female offspring exhibited elevations in anti-inflammatory transcripts, and HFD male offspring responded with a larger pro-inflammatory response to simultaneous CORT and LPS administration. These findings suggest that exposure to maternal HFD leads to sex-specific alterations that could regulate the neural immune response, possibly as an adaptive response to basal inflammation.