1923-P: Ablating Mitochondrial Creatine Kinase Does Not Affect Energy Expenditure, White Adipose Tissue, Mitochondrial Respiration, or the Susceptibility to High-Fat Diet-Induced Obesity
Bibliographic record
Abstract
Introduction: Recently, creatine (Cr) mediated ’recycling’ of ADP was proposed to promote energy expenditure (EE) within white adipose tissue (WAT). We determined the influence of ablating mitochondrial creatine kinase (Mi-CK), an enzyme necessary to the proposed Cr cycling, to ascertain the biological importance of Cr-mediated EE in the development of high-fat diet (HFD)-induced obesity. Methods: Female Mi-CK wild type (WT) and knock-out mice (n=6-8/group) were randomized to receive control (10% fat) or HFD (60% fat) for 8 weeks. Whole-body indirect calorimetry (EE, RER) and glucose tolerance were determined. Inguinal WAT (iWAT) and gonadal WAT (gWAT) were used to determine mitochondrial oxidative phosphorylation (OXPHOS) proteins and submaximal (100 μM ADP) and maximal (5 mM ADP) respiration in the presence and absence of Cr (0.01mM). Results: In WT animals, HFD consumption increased body mass and whole-body fat oxidation, while decreasing rates of carbohydrate oxidation and glucose tolerance. HFD reduced mass-specific iWAT and gWAT submaximal and maximal ADP-supported respiration ∼50%. HFD also reduced WAT OXPHOS protein content ∼25%, however normalizing respiration to OXPHOS protein did not mitigate the observed HFD-induced reduction in respiration, suggesting an attenuation in mitochondrial-specific respiration. The presence of Cr did not drive respiration in any experiment, challenging the notion that Cr stimulates mitochondrial respiration. In further support of this finding, ablating Mi-CK did not influence HFD-induced weight gain, whole body EE, the development of glucose intolerance or respiratory function in either iWAT or gWAT depots. Conclusion: Ablating Mi-CK does not affect HFD-induced phenotypic changes, suggesting Cr-mediated EE is not a primary determinant in the development of obesity-induced glucose intolerance. Disclosure V. Politis-Barber: None. H.L. Petrick: None. G. Holloway: None. Funding Natural Sciences and Engineering Research Council of Canada (400360)
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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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.012 | 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".