Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring
Bibliographic record
Abstract
BACKGROUND: Maternal obesity as a result of high levels of saturated fat (HFD) consumption leads to significant negative health outcomes in both mother and exposed offspring. Offspring exposed to maternal HFD show sex-specific alterations in metabolic, behavioral, and endocrine function, as well as increased levels of basal neuroinflammation that persists into adulthood. There is evidence that psychosocial stress or exogenous administration of corticosterone (CORT) potentiate inflammatory gene expression; however, the response to acute CORT or immune challenge in adult offspring exposed to maternal HFD during perinatal life is unknown. We hypothesize that adult rat offspring exposed to maternal HFD would show enhanced pro-inflammatory gene expression in response to acute administration of CORT and lipopolysaccharide (LPS) compared to control animals, as a result of elevated basal pro-inflammatory gene expression. To test this, we examined the effects of acute CORT and/or LPS exposure on pro and anti-inflammatory neural gene expression in adult offspring (male and female) with perinatal exposure to a HFD or a control house-chow diet (CHD). METHODS: Rat dams consumed HFD or CHD for four weeks prior to mating, during gestation, and throughout lactation. All male and female offspring were weaned on to CHD. In adulthood, offspring were 'challenged' with administration of exogenous CORT and/or LPS, and quantitative PCR was used to measure transcript abundance of glucocorticoid receptors and downstream inflammatory markers in the amygdala, hippocampus, and prefrontal cortex. RESULTS: In response to CORT alone, male HFD offspring showed increased levels of anti-inflammatory transcripts, whereas in response to LPS alone, female HFD offspring showed increased levels of pro-inflammatory transcripts. In addition, male HFD offspring showed greater pro-inflammatory gene expression and female HFD offspring exhibited increased anti-inflammatory gene expression in response to simultaneous CORT and LPS administration. CONCLUSIONS: These findings suggest that exposure to maternal HFD leads to sex-specific changes that may alter inflammatory responses in the brain, possibly as an adaptive response to basal neuroinflammation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".