Arginylation regulates adipose tissue development and function via modulating PPARγ expression
Bibliographic record
Abstract
Arginylation, a poorly understood post translational modification mediated by ATE1 known to regulate protein activity and stability Unconditional deletion of Ate1 results in embryonic lethality and postnatal whole body deletion of Ate1 in mouse results in adipose tissue dysfunction i.e. loss of visceral fat, exhibit higher metabolic rate and resistant to diet induced obesity Adipose tissue dysregulation leads to various life threatening diseases like obesity, diabetes, cardiovascular defects and cancer Current study is undertaken to understand the role of protein arginylation in adipose tissue development and function. Our initial investigation showed an increase in ATE1 protein expression with progression of adipogenesis in 3t3L1 preadipocyte differentiation. Further, treatment of these cells with ATE1 inhibitors, tannic (10 M) acid and merbromin (75 M) suppressed lipid accumulation in 3t3l1 cell significantly. Gene expression analysis shows inhibition of peroxisome proliferator activated receptor gamma (PPAR) 1 and PPAR2 expression in 3t3l1 cells differentiated in presence of ATE1 inhibitors. PPAR is a key transcription factor of adipogenesis and plays crucial role in induction of various adipogenic genes which contributes to lipid formation. The mRNA level of PPAR associated genes glucose transporter 4 (GLUT4), fatty acid binding protein 4 (FABP4) and perilipin (pln1) were found to be downregulated by ATE1 inhibitors, hence results into decrease in lipid accumulation. As PPAR found to be a target for ATE1 inhibitors, PPAR1 was overexpressed in Ate1 knockout (KO1) and wild type mouse embryonic fibroblast (MEF) cells. Expression of PPAR1 was found to be significantly low in KO1 as compared to its wild type counterpart at transcript level. Interestingly inhibition of PPAR1 expression in absence of arginylation becomes more profound at protein level. Low level of PPAR1 impedes adipogenesis when KO1 cells were induced to differentiation with poor induction of GLUT4, lipoprotein lipase and FABP4. Current study provides a new protein arginylation dependent adipogenic pathway which promotes adipogenesis by promoting PPAR.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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".