APPL1 transgenic mice are protected from high-fat diet-induced cardiac dysfunction
Bibliographic record
Abstract
APPL1 (adaptor protein containing PH domain, PTB domain, and leucine zipper motif 1) has been established as an important mediator of insulin and adiponectin signaling. Here, we investigated the influence of transgenic (Tg) APPL1 overexpression in mice on high-fat diet (HFD)-induced cardiomyopathy in mice. Wild-type (WT) mice fed an HFD for 16 wk showed cardiac dysfunction, determined by echocardiography, with decreased ejection fraction, decreased fractional shortening, and increased end diastolic volume. HFD-fed APPL1 Tg mice were significantly protected from this dysfunction. Speckle tracking echocardiography to accurately assess cardiac tissue deformation strain and wall motion also indicated dysfunction in WT mice and a similar improvement in Tg vs. WT mice on HFD. APPL1 Tg mice had less HFD-induced increase in circulating nonesteridied fatty acid levels and myocardial lipid accumulation. Lipidomic analysis using LC-MS-MS showed HFD significantly increased myocardial contents of distinct ceramide, sphingomyelin, and diacylglycerol (DAG) species, of which increases in C16:0 and C18:0 ceramides plus C16:0 and C18:1 DAGs were attenuated in Tg mice. A glucose tolerance test indicated less peripheral insulin resistance in response to HFD in Tg mice, which was also apparent by measuring cardiac Akt phosphorylation and cardiomyocyte glucose uptake. In summary, APPL1 Tg mice exhibit improved peripheral metabolism, reduced cardiac lipotoxicity, and improved insulin sensitivity. These cellular effects contribute to protection from HFD-induced 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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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 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".