1875-P: Liver-Specific p38 MAPK Stimulates Hepatic Fat Accumulation and Reduces Insulin Sensitivity In Vivo
Bibliographic record
Abstract
Insulin resistance and hepatic fat accumulation are features of metabolic syndrome, although the mechanisms remain unclear. The cellular-stress responsive kinase, p38 Mitogen Activated Protein Kinase (p38), has controversial roles in regulating glucose and lipid metabolism in vivo. Here we show that liver-specific p38 stimulates hepatic triglyceride accumulation and contributes to the development of high fat diet (HFD)-induced insulin resistance. Liver-specific p38 knockout mice (p38KO) and wild type controls (WT) were fed a HFD or control diet for one week. Glucose tolerance tests revealed that HFD-fed p38KO mice had improved glucose tolerance compared to HFD-fed WT mice. Moreover, hyperinsulinemic-euglycemic clamps were performed to assess insulin sensitivity. HFD-fed p38KO mice were protected from reduced whole-body insulin action seen in HFD-fed WT mice, having similar glucose infusion rates as WT mice fed a control diet. To assess hepatic triglyceride accumulation, liver sections were stained with Oil Red-O post diet treatment. HFD-fed WT mice had significantly greater hepatic triglycerides, represented as a percentage of total liver area, compared to HFD-fed p38KO mice. In accordance with reduced hepatic triglyceride accumulation, decreasing trends in triglyceride secretion rates and plasma ApoB protein expression were reported between HFD-fed p38KO and HFD-fed WT mice following Poloxamer-407 injections. Overall, our data suggest that genetic inhibition of hepatic p38 may provide benefit in controlling heightened hepatic fat accumulation and reduced insulin sensitivity observed in HFD models. Disclosure S.L. Rivers: None. H. Wang: None. L. Lam: None. A. Giacca: Research Support; Self; Jazz Pharmaceuticals. Funding Canadian Institutes of Health Research
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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 | 0.000 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 0.002 |
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".