Beige fat is dispensable for the metabolic benefits associated with myostatin deletion
Bibliographic record
Abstract
OBJECTIVE: Increasing muscle mass and activating beige fat both have great potential for ameliorating obesity and its comorbidities. Myostatin null mice have increased skeletal muscle mass and are protected from obesity and its sequelae. Deletion of myostatin has also been suggested to result in the activation of beige adipocytes, thermogenic fat cells with anti-obesity and anti-diabetes properties. It is not known whether beige fat activation contributes to the protection from obesity in myostatin null mice. METHODS: To investigate the role of beige fat activation in the metabolic benefits associated with myostatin deletion, we crossed myostatin null mice to adipocyte-specific PRDM16 knockout mice. We analyzed this new mouse model using molecular profiling, whole mount three-dimensional tissue imaging, tissue respiration, and glucose and insulin tolerance tests in models of diet-induced obesity. RESULTS: Here, we report that PRDM16 is required for the activation of beige fat in the absence of myostatin. However, we show in both male and female mice that beige fat activation is dispensable for the protection from obesity, glucose intolerance, insulin resistance, and hepatic steatosis mediated by myostatin deletion. CONCLUSION: These findings demonstrate that increasing muscle mass can compensate for the inactivation of beige fat and raise the possibility of targeting muscle mass as a therapeutic approach to offset the deleterious effects of adipose tissue dysfunction in obesity and metabolic syndrome.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| 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".