Nitric oxide mediates endotoxin‐induced hypertriglyceridemia through its action on skeletal muscle lipoprotein lipase
Bibliographic record
Abstract
ABSTRACT Hypertriglyceridemia (hyperTG) is a common characteristic of endotoxemia. At high doses of endotoxin, hyperTG is caused by a reduction in the activity of lipoprotein lipase (LPL), the enzyme responsible for TG intravascular clearance. The present studies were aimed at evaluating the role of nitric oxide (NO), overproduced in endotoxemia through the activation of inducible NO synthase (iNOS), in the decrease in tissue LPL activity brought about by lipopolysaccharide (LPS, 15 mg/kg). In rats, the specific iNOS inhibitor aminoguanidine (AGN, 100 mg/kg) prevented the LPS‐induced threefold elevation in plasma TG concentration, through actions that were not related to changes in hepatic TG secretion. AGN administration abrogated the LPS‐induced reduction in LPL activity in skeletal muscle but not that in white adipose tissue (WAT). Quantification of LPL mRNA revealed that AGN prevented LPS‐mediated alterations in muscle LPL activity through posttranscriptional mechanisms. The above findings were confirmed in iNOS (‐/‐) knockout mice injected with endotoxin. LPS increased plasma TG concentration in wild‐type mice by 75%, whereas hyperTG did not occur in knockout mice. Skeletal muscle LPL activity decreased by 40% in wild‐type mice but remained unchanged in knockout mice 6 h after LPS injection, whereas WAT LPL activity decreased to one‐third of control levels in both genotypes. These findings demonstrate that, after LPS administration, reduced muscle LPL activity and the resulting hyperTG are caused by the overproduction of NO via the induction of iNOS. The findings further provide evidence for a central role of muscle LPL in the response of TG metabolism to acute endotoxemia.
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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 | 0.001 | 0.001 |
| 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 | 0.001 |
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 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".