Prolonged saturated, but not monounsaturated, high-fat feeding provokes anxiodepressive-like behaviors in female mice despite similar metabolic consequences
Bibliographic record
Abstract
Obesity significantly increases the risk for anxiety and depression. Our group has recently demonstrated a role for nucleus accumbens (NAc) pro-inflammatory nuclear factor kappa-B (NFkB) signaling in the development of anxiodepressive-like behaviors by diet-induced obesity in male mice. The NAc is a brain region involved in goal-oriented behavior and mood regulation whose functions are critical to hedonic feeding and motivation. While the incidence of depression and anxiety disorders is significantly higher in women than in men, the use of female animal models in psychiatric research remains limited. We set out to investigate the impact of chronic intake of saturated and monounsaturated high-fat diets (HFD) on energy metabolism and on anxiety- and despair-like behaviors in female mice and to ascertain the contribution of NAc NFkB-mediated inflammation herein. Adult C57Bl6N female mice were fed either a saturated HFD, an isocaloric monounsaturated HFD or a control low-fat diet for 24 weeks, after which metabolic profiling and behavioral testing for anxiodepressive-like behaviors were conducted. Plasma was collected at time of sacrifice for quantification of leptin, inflammatory markers as well as 17 β-estradiol levels and brains were harvested to analyze NAc expression of pro-inflammatory genes and estrogen-signaling molecules. In another group of female mice placed on the saturated HFD or the control diet for 24 weeks, we performed adenoviral-mediated invalidation of the NFkB signaling pathway in the NAc prior to behavioral testing. While both HFDs provoked obesity and metabolic impairments, only the saturated HFD triggered anxiodepressive-like behaviors and caused marked elevations in plasma estrogen. This saturated HFD-specific behavioral phenotype could not be explained by NAc inflammation alone and was unaffected by NAc invalidation of the NFkB signaling pathway. Instead, we found changes in the expression of estrogen signaling markers. Such results diverge from the inflammatory mechanisms underlying diet- and obesity-induced metabolic dysfunction and anxiodepressive-like behavior onset in male mice and call attention to the role of estrogen signaling in diet-related anxiodepressive-like phenotypes in female mice.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".