Abstract 868: A Cardiac Specific Branched Chain Aminotransferase Deletion Increases Insulin Stimulated Glucose Oxidation in the Mouse Heart
Bibliographic record
Abstract
Impaired branched chain amino acid (BCAA) oxidation at the level of downstream BCAA catabolic enzymes cause cardiac insulin resistance and dysfunction. However, it is not known whether it is the accumulation of BCAAs or branched chain keto acids (BCKAs) due to impaired cardiac BCAA oxidation that result in these cardiac metabolic detrimental effects. Our objective was to inhibit cardiac branched chain aminotransferase (BCATm), the first enzyme in the BCAA oxidative pathway, which functions to produce BCKAs. We anticipate deletion of upstream BCAA catabolic enzyme will result in reduced cardiac BCAA oxidation and increase BCAAs but decrease BCKAs. Ten-week-old BCATm cardiac specific knockout (BCATm -/- ) male mice and their α-MHC-Cre expressing wildtype littermates (WT-Cre +/+ ) received 6 intraperitoneal injections of tamoxifen (50 mg/kg). All mice were allowed a 6-week washout post-tamoxifen, following which 16-week-old mice were used to assess cardiac energy metabolism. Isolated working hearts were perfused with oxygenated Krebs–Henseleit solution, consisting of either 5mM [5- 3 H/U- 14 C] glucose, 0.8mM palmitate, 3%BSA, 0.5mM BCAA for glycolysis and glucose oxidation measurements, or 0.5mM glucose, 0.8mM [9,10- 3 H] palmitate, 3%BSA and 0.5mM [U- 14 C] BCAA from combination of 0.15mM leucine/isoleucine and 0.2mM valine for fatty acid oxidation and BCAA oxidation measurements respectively. There was no body weight, glucose tolerance or cardiac function differences observed in BCATm -/- mice compared to WT-Cre +/+ mice (control). As expected, cardiac BCAA oxidation was significantly reduced in BCATm -/- mice compared to control, however, adding insulin after 30 min of perfusion did not change BCAA oxidation rates. Interestingly, glucose oxidation was significantly higher in BCATm -/- mice. Adding insulin further increased glucose oxidation in BCATm -/- mice. Additionally, the contribution of glucose oxidation to ATP production was significantly higher in the BCATm -/- mice compared to control. We conclude that impaired BCAA oxidation due to the upstream catabolic enzyme deletion increases cardiac insulin sensitivity. This also indicates that accumulation of BCKAs, not BCAAs, may be primarily contributing to cardiac insulin resistance.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.003 |
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".