Paradoxical Effects of Fenofibrate and Nicotinic Acid in Apo E-Deficient Mice
Bibliographic record
Abstract
Atherosclerosis is a complex vascular disease initiated by abnormal accumulation of plasma lipoproteins in the subendothelial space. Elevated levels of plasma triglycerides (TG) and low-density lipoprotein (LDL)-cholesterol as well as low concentrations of high-density lipoprotein (HDL) play a causal role in the development and progression of atherosclerotic lesions. We have shown that apolipoprotein E-deficient (apo E-KO) mice have elevated triglyceride levels plus diminished HDL concentrations. Drugs such as fenofibrate and nicotinic acid are well known to reduce TG and increase HDL levels in humans. In this study, we investigated the beneficial effects of fenofibrate and niacin on lipid profile and atherogenesis in apo E-KO mice and their wild-type counterparts. Animals were fed with a cholesterol-enriched diet supplemented with fenofibrate (0.1% wt/wt, n = 8) or nicotinic acid (0.5% wt/wt, n = 8) for 14 weeks. Body weights were recorded weekly, and plasma lipid profiles were determined at 4-week intervals. The hearts and aortas were collected and fixed for histologic and morphometric evaluations of atherosclerotic lesions. Fenofibrate treatment in apo E-KO mice paradoxically increased total cholesterol and TG by 65% and 44%, respectively, and decreased HDL-cholesterol levels by 35% as compared with controls. Similar effects of fenofibrate on cholesterol levels, but not on TG concentrations, were observed in C57BL/6 mice. Fenofibrate-treated mice had lower body weight as compared with controls. Niacin had no effect on body weight gain but failed to decrease TG or to increase HDL levels in either apo E-KO mice or their wild-type counterparts. Neither fenofibrate nor niacin significantly influenced atherogenesis in apo E-KO mice as compared with controls. In conclusion, this study shows that neither niacin nor fenofibrate has beneficial lipid-modifying and antiatherosclerosis activities in mice. Identification of mechanisms underlying paradoxical effects of fenofibrate on lipoprotein metabolisms in apo E-KO mice merits further investigation.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.000 |
| 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".