Abstract 6255: Adiponectin Deficiency Profoundly Exacerbates Sepsis-Related Mortality through Endothelial Activation: A Novel Mechanistic Link between Adiposity and Sepsis
Bibliographic record
Abstract
INTRODUCTION: Sepsis is a multifactorial, and often fatal disorder, characterized by widespread inflammation with resultant endothelial activation. Adiposity and diabetes are strong negative predictors of sepsis related cardiovascular dysregulation and mortality, however, the mechanisms remain unclear. We postulated that alterations in adipokine biology, particularly adiponectin, are essential modulators of survival and endothelial activation in sepsis. METHODS AND RESULTS: We evaluated both loss-of-function (adiponectin gene-deficient mice) and subsequent gain-of-function (recombinant adiponectin reconstitution) strategies in two well-established inflammatory models, cecal ligation perforation (CLP) and thioglyocollate-induced peritonitis. Adipoq −/− mice, subjected to CLP, exhibited a profound (~8 fold) reduction in survival compared to their wild-type Adipoq −/− littermates after 48 hours. Furthermore, compared to wild-type controls, thioglycollate challenge resulted in a markedly greater influx of peritoneal neutrophils in Adipoq −/− mice accompanied by an excess production of key chemoattractant cytokines (IL-12p70, TNFalpha, MCP-1 and IL-6) and upregulation of aortic endothelial adhesion molecule expression, VCAM-1 and ICAM-1. Importantly, all of these effects were blunted by recombinant total adiponectin administration given three days prior to thioglycollate challenge. The protective effects of adiponectin were largely ascribed to higher order adiponectin oligomers, since administration of recombinant trimeric adiponectin did not attenuate endothelial adhesion molecule expression in thioglycollate-challenged Adipoq −/− mice. CONCLUSIONS: These data suggest a critical role of adiponectin as a modulator of survival and endothelial inflammation in experimental sepsis and suggest one of the first mechanistic links between adiposity and sepsis related death.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".