Cardiac Peroxisome Proliferator‐activated Receptor‐β Activity is Up‐regulated in the Absence of Muscle RING Finger‐3, and Exaggerates High‐fat Diet‐induced Cardiomyopathy
Bibliographic record
Abstract
Diabetic cardiomyopathy is characterized by structural and functional alterations leading to cardiac hypertrophy and heart failure. These changes are regulated in part by PPAR signaling and subsequent changes in fatty acid metabolism. We recently identified that mice lacking ubiquitin ligase Muscle RING Finger‐3 (MuRF3‐/‐) have increased cardiac PPAR‐β activity in vivo . We hypothesized that challenging MuRF3‐/‐ mice with a high‐fat diet, where lipids act as PPAR ligands, would enhance the severity of diabetic cardiomyopathy. MuRF3‐/‐ mice and strain‐matched controls were fed a high‐fat diet. Serum insulin and glucose were measured every two weeks. Total cholesterol and serum triglycerides (TG) were measured at baseline and 26 weeks. Echocardiography was performed every three weeks. MuRF3‐/‐ mice have less blood glucose after 26 weeks on high fat diet (HFD) as compared to strain‐matched controls (168.8±6.2 vs. 240.2±15.5 mg/dL, P<0.05) and increased fasting insulin levels relative to controls (4.7±0.3 vs. 3.4±0.2 ng/ml, P<0.05). Knockout mice do not show differences in fasting total cholesterol or serum TG compared to wild‐type mice at any timepoint. By echocardiography, MuRF3‐/‐ mice have depressed fractional shortening at 6 weeks HFD compared to wild‐type mice (43.6±6.1% vs. 49.2±3.5%, P<0.05). Mice lacking MuRF3 demonstrate exaggerated cardiomyopathy in the presence of high‐fat diet. Increased PPAR‐β activity and fatty acid metabolism are known contributors to diabetic cardiomyopathy. Taken together, these findings corroborate a novel role for MuRF3 in protecting against the development of diabetic cardiomyopathy.
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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 | 0.001 | 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) | 0.002 | 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".