Abstract 576: The Role of Adipose Derived Autotaxin on Inflammation Associated with Cardiovascular Disease
Bibliographic record
Abstract
Obesity is an established risk factor for cardiovascular disease (CVD) and stroke, and the cardiovascular complications of obesity are a leading cause of potentially preventable death. Recent evidence suggests that increased cardiovascular mortality in patients with obesity may not be fully explained by associated risk factors such as dyslipidemia, hyperglycemia, insulin resistance and hypertension. In addition to contributing to traditional CVD risk factors, obesity is also characterized by a chronic sub-acute inflammatory state termed “metainflammation” involving increased circulating inflammatory cytokines. Autotaxin (ATX), encoded by the ecto-nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) gene, is a potent cell motility-stimulating factor that is secreted by adipose tissue. ATX hydrolyzes lysophosphatidylcholine (LPC), a lipid that is abundant in the circulation, to lysophosphatidic acid (LPA). The main objective of this study was to explore whether adipose ATX contributes to systemic inflammatory responses in obesity. We established two animal models with reduced ATX expression: MX-1 Cre-mediated deletion of the ENPP2 gene to generate a global ATX loss (Mx1) and Adipoq-Cre mediated loss of ATX expression in adipocytes (AdipoQ). Mice were fed a high fat diet for up to 20 weeks. No differences in body weight between the ENPP2 loss and littler mate controls were found. RNA and proteins were extracted, qPCR and western blots were performed for ATX and inflammatory cytokines; MCP, TNF and IFN. Results demonstrate that mice lacking global or adipose-derived ATX display approx 2 fold lower adipose inflammation. Furthermore, LPS was used to provoke a systemic response in mice that had been on a HFD for 10 weeks. Six hours after LPS injection, RNA was extracted and qPCR performed for IL6, IL1beta and IFN gamma. In response to a LPS challenge, AdipoQ mice showed a 2 fold reduction in inflammatory response in adipose tissue. The data generated from these experiments will provide important insight into potential mechanisms of how ATX and adipose tissue influence obesity induced inflammation and results from this and future projects may identify potential therapeutic targets to prevent and treat obesity induced inflammation and CVD.
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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 | 0.001 | 0.001 |
| 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 | 0.001 |
| 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".