Discoidin domain receptor 1-deletion ameliorates fibrosis and promotes adipose tissue beiging, brown fat activity, and increased metabolic rate in a mouse model of cardiometabolic disease
Bibliographic record
Abstract
OBJECTIVE: Discoidin domain receptor 1 (DDR1) is a collagen binding receptor tyrosine kinase implicated in atherosclerosis, fibrosis, and cancer. Our previous research showed that DDR1 could regulate smooth muscle cell trans-differentiation, fibrosis and calcification in the vascular system in cardiometabolic disease. This spectrum of activity led us to question whether DDR1 might also regulate adipose tissue fibrosis and remodeling. METHODS: We have used a diet-induced mouse model of cardiometabolic disease to determine whether DDR1 deletion impacts upon adipose tissue remodeling and metabolic dysfunction. Mice were fed a high fat diet (HFD) for 12 weeks, followed by assessment of glucose and insulin tolerance, respiration via indirect calorimetry, and brown fat activity by FDG-PET. RESULTS: mice also had reduced fibrosis, smaller adipocytes with multilocular lipid droplets, and increased UCP-1 expression characteristic of beige fat formation in subcutaneous adipose tissue. In vitro, studying C3H10T1/2 cells stimulated to differentiate, DDR1 inhibition caused a shift from white to beige adipocyte differentiation, whereas DDR1 expression was increased with TGFβ-mediated pro-fibrotic differentiation. CONCLUSION: This study is the first to identify a role for DDR1 as a driver of adipose tissue fibrosis and suppressor of beneficial beige fat formation.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 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".