ABSTRACT
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.
ABBREVIATIONS
- ANOVA
- Analysis of variance
- CD11B
- Cluster of differentiation molecule B
- CHD
- Control house-chow diet
- CORT
- Corticosterone
- GAPDH
- Glyceraldehyde 3-phosphate dehydrogenase
- HFD
- High-fat diet
- HPA
- Hypothalamic-pituitary-adrenal
- HPC
- Hippocampus
- IGF1
- Insulin-like growth factor 1
- IκBα
- Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
- IL6
- Interleukin 6
- IL10
- Interleukin 10
- GR
- Glucocorticoid receptor
- LPS
- Lipopolysaccharide
- MKP1
- Mitogen-activated protein kinase phosphatase 1
- MR
- Mineralocorticoid receptor
- NFκB
- Nuclear factor kappa-beta-light-chain-enhancer of activated B cells
- PFC
- Prefrontal cortex
- PND
- Post-natal day
- qPCR
- Quantitative polymerase chain reaction
- SEM
- Standard error of mean
- YWHAZ
- Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase Activation Protein Zeta