Abstract 847: Adipocyte-specific Pharmacological Inhibition of Adipose Triglyceride Lipase (ATGL) Ameliorates Cardiac Fibrosis in Heart Failure
Bibliographic record
Abstract
Objectives: ATGL is a key enzyme that regulates triglyceride lipolysis in most cells, including the adipocyte and the cardiomyocyte. Recent studies indicate that accelerated adipose tissue lipolysis contributes to worsening heart failure (HF), suggesting that ATGL inhibition specifically in the adipocyte may prevent worsening HF. Indeed, we have shown that the ATGL inhibitor, Atglistatin, which appears to be largely adipocyte-specific, ameliorates cardiac dysfunction and hypertrophy in HF induced by transverse aortic constriction (TAC). However, the mechanisms by which Atglistatin treatment prevents worsening HF in mice remains unknown. Methods: Eight week-old C57BL/6N mice underwent TAC or sham surgery. After 1 week, mice with HF were assigned into 4 groups: 1) vehicle (standard chow)-sham, 2) Atglistain-sham, 3) vehicle-TAC and 4) Atglistatin-TAC. Atglistain was administered in food pellets containing 2mmol Atglistatin/kg for 2 weeks. Thereafter, mice were euthanized and hearts were used for subsequent histological and quantitative PCR analysis. Results: Picro-sirius red staining demonstrated that hearts from the Atglistatin TAC mice had significantly less cardiac fibrosis than the vehicle TAC mice (1.6±0.4 vs 5.3±1.1%, in Atglistatin TAC vs vehicle TAC; p<0.01). Consistent with this finding, Atglistatin treatment of the TAC group reduced transcript levels of fibrosis-related genes, including Col1a1 (-58.7%, p=0.03) and Postn (-54.7%, p<0.01), compared to vehicle-treated hearts. Furthermore, Atglistatin decreased the transcript levels of the macrophage polarization-related genes, including Lgals3 (-55.3%, p<0.01) and Spp1 (-38.7%, p=0.03) , in the hearts from TAC mice compared to controls. Moreover, immunofluorescent analysis showed that Atglistatin reduced infiltration of Galectin-3 positive macrophages in the heart compared to vehicle-TAC mice, suggesting reduced macrophage infiltration and activation and less cardiac fibrosis. Conclusion: Our data indicate that reducing triglyceride lipolysis in the adipose tissue via ATGL inhibition may ameliorate HF via modulation of HF-induced macrophage and fibroblast activation in the heart.
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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 | 0.001 | 0.001 |
| 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 | 0.000 |
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".