The alternative complement system and obesity: using knockout mouse models to investigate fat metabolism (96.24)
Bibliographic record
Abstract
Abstract A growing body of evidence now links immunology and metabolic functions. The alternative system plays a role in injury and tissue damage as assessed by complement 3 knockout (C3KO), factor B (FBKO) and factor D (FDKO) mice with injury and septic shock. Recently the C5L2 receptor was found to act as a decoy receptor for C5a during similar conditions. Acylation stimulating protein (C3adesArg/ASP), a by-product of the alternative complement pathway also acts via C5L2 to stimulate triglyceride (TG) synthesis in adipose tissue. Wildtype (WT), C3KO, FBKO and C5L2KO mice on a normal chow diet were studied over 12 weeks. No difference in body weight was observed between KO and WT mice. However C3KO, FBKO and C5L2KO mice displayed increased food intake by 56%, 48% and 62% respectively vs. WT mice (p<0.05). Consistent with previous findings, C3KO mice showed delayed TG clearance during a fat load. FBKO and C5L2KO mice also display delayed postprandial lipemia. Adipose tissue from C5L2KO mice showed reduced ex vivo TG synthesis (-83%, p<0.001). Also, DGAT (TG synthesis enzyme) activity and protein were significantly reduced in C3KO mice vs. WT. Therefore, under normal physiological, alternative complement KO mice display altered fat metabolism. We attribute this phenotype to the lack of ASP and C5L2 signalling, however, further investigation is still required to understand the association between immunity and metabolism. Funding: CIHR and NSERC
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".