Abstract 477: Adipocyte Twist-1 Deficiency Exacerbates Weight Gain, Glucose Intolerance and Adipose Tissue Inflammation in Females
Bibliographic record
Abstract
Twist1 is a transcription factor abundantly expressed by adipocytes, immune and vascular cells in adipose tissue (AT) in humans and rodents. Low twist1 expression in human AT is correlated with insulin resistance and obesity. However the role of twist-1 in different cell types component of AT is not clear. The objective of this study was to determine the role of adipocyte (Adp) twist-1 in obesity and insulin resistance. Adp-specific twist1 knock out mice ( AdiponectinCreTwistflox ) (n=6) on the C57Bl6/J background were maintained on 60%kcal fat diet for 12 weeks. Compared to littermate controls (n=6), the female mutant mice, but not the males, showed a 3- and 1.5- fold increase in visceral and subcutaneous adiposity, respectively. Similarly, only the mutant females had significantly impaired glucose tolerance (P<0.05) compared to the littermate controls. Peri-gonadal AT in mutant females showed increased CD11b+F4/80+ and CD3+CD8+ numbers compared to controls, however no differences were found between the male mice. The female mutant mice had more hypertrophied Adp and displayed a 2-4-fold increase in gene expression of IFN γ, TNF α, CD3e and Jak2 compared to controls. Also, expression of the lipogenic enzymes Acaca and Acls4 were significantly reduced by 2.2-fold in the mutant females. Interestingly expression of Nampt (visfatin) gene was significantly increased in mutant females compared to both controls and mutant males. Importantly, twist1 expression in visceral Adp of obese human females (n=15) and males (n=8) at the time of bariatric surgery was significantly higher in females (p<0.01). Also, in a longitudinal cohort at ~1.2 years following surgical weight loss, twist1 expression was significantly increased in visceral AT of males (n=3) (p<0.05) but not in females (n=6) despite a similar reduction in body weight. Collectively the rodent data suggest that twist1 deficiency in Adp increases AT inflammation and exacerbates adiposity and glucose intolerance only in females and identifies visfatin as a metabolically relevant gene potentially regulated by twist1 in females. Also, obese human females may be protected by constitutively higher expression of twist1 in visceral Adp and surgical weight loss leads to increased twist1 expression in males.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.011 | 0.002 |
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".