Abstract 16082: Plin2 Attenuates Cardiomyocyte Lipotoxicity
Bibliographic record
Abstract
Diabetic cardiomyopathy is associated with excess lipid accumulation in the heart. We previously showed that oleate, a non-toxic mono-unsaturated fatty acid causes the formation of abundant lipid droplets in cardiomyocytes that were lined with Plin2, an important lipid droplet binding protein. In contrast, palmitate, a toxic saturated fatty acid, led to the formation of aberrant lipid droplets which lacked Plin2 immunoreactivity. Hypothesis: We hypothesized that Plin2 overexpression may protect against palmitate mediated lipotoxicity. Methods: We overexpressed and silenced Plin2 in rat neonatal cardiomyocytes (NCMs) by LentiVector mediated overexpression of Plin2 cDNA and shRNAs, respectively. We treated these NCMs with bovine serum albumin (51μM, vehicle control), 100-300μM oleate, or 100-300μM palmitate for 4-24 hours. We evaluated viability with the propidium iodide exclusion assay and measured gene expression by qRT-PCR. Results: Plin2 overexpression protected NCMs from the lipotoxic effects of palmitate. Conversely, silencing of Plin2 sensitized NCMs to the effects of palmitate and caused oleate, which is normally non-toxic, to induce cell death in NCMs. Interestingly, we found that Plin2 overexpression had a marked stimulatory effect on several PPAR target genes including Carnitine palmitoyl transferase 1b (Cpt1b), the rate limiting enzyme in β-oxidation. In contrast, Plin2 silencing led to a significant decrease in oleate induced expression of PPAR target genes, including Cpt1b. Conclusion: Here we showed that overexpression of Plin2, a key lipid droplet binding protein protected against lipotoxicity, while silencing it caused lipotoxicity. We show that this may be due to alterations in lipid metabolism, since Plin2 overexpression led to increased expression of key β-oxidation genes. This is important because we have previously shown that palmitate impairs β-oxidation capacity in cardiomyocytes. Therefore enhancing β-oxidation may attenuate lipotoxicity by limiting the build-up of lipid metabolites. The mechanism of Plin2 mediated effects on PPAR target gene expression, as well as the effect on lipid droplet formation are the subject of on-going studies.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".