Critical Role Of MCP‐1 In n‐6 Polyunsaturated Fatty Acids (PUFA)‐Induced Cardiac ER Stress In Diet‐Induced Obesity
Bibliographic record
Abstract
Pathways by which excess n‐6 PUFAs promotes cardiac inflammation and apoptosis is unclear. We predicted a role for ER stress in inducing such cardiotoxicity. Female C57/Bl6 mice were fed normal chow or high‐fat (40%) diets rich either in n‐6 PUFA or monounsaturated fatty acids (MUFA) for 5 weeks. Immunoblotting revealed upregulation of proteins like IRE‐1α, BiP, PERK and calnexin in the heart of n‐6 PUFA but not in MUFA fed hearts. Further, upregulation of CHOP‐1, caspase‐12, TUNEL and ubiquitinated protein expressions confirmed elevated apoptosis in n‐6 PUFA fed hearts. Interestingly, MCPIP [monocyte chemotactic protein‐1 (MCP‐1) induced protein], a nuclear transcription factor was also induced with n‐6 PUFA. As MCP‐1 is key in cardiac inflammation we hypothesized that n‐6 PUFA triggers cardiac ER stress in an MCP‐1 dependent manner. MCP‐1 −/− mice hearts demonstrated significantly less ER stress and undetectable MCPIP levels in response to high n‐6 PUFA than MCP‐1 +/+ hearts. Deletion of MCP‐1 also attenuated CHOP‐1, caspase‐12 and ubiquitinated proteins in response to n‐6 PUFA. These results indicate that dietary excess of n‐6 PUFA may lead to cardiac ER stress and apoptosis during diet induced obesity via MCP‐1 signaling. These data may provide an insight into possible mechanisms for cardiotoxicity of dietary oils like corn and sunflower oils in the western diet.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".