The role of SCFAs to reduce endotoxin and asprosin induced inflammation in human lung epithelial and adipocyte cells
Bibliographic record
Abstract
Weight gain in obesity is known to exacerbate chronic inflammation, which in turn may worsen symptoms related to comorbidities including asthma. The source of this inflammation may arise internally, due to pro-inflammatory adipokines or gut permeability, which allows pro-inflammatory factors to cross into the bloodstream Endotoxin, found on the outer membrane of gram-negative bacteria, is known to induce inflammation in obesity A novel adipokine asprosin is also increased in obesity and may exacerbate other inflammatory diseases Current treatments for asthma only relieve symptoms rather than targeting inflammation at the source. Prebiotics may offer a dietary method to mitigate inflammation directly through the improvement of gut heath, reducing the severity of associated diseases. Prebiotics are non-digestible carbohydrates that increase the number of beneficial bacteria in the gut and produce anti-inflammatory metabolites called short chain fatty acids (SCFAs). This study aims to determine the role of SCFAs (acetate, butyrate, and propionate) on endotoxin and asprosin induced inflammation in lung and adipose tissue, in order to explore the mechanisms of prebiotics as a potential treatment for asthma. Human airway epithelial cells (BEAS2B-R1) and human adipocytes (Chub-S7) were treated over time (6, 12, 24hrs) with 100ng/mL endotoxin (lipopolysaccharide; LPS) or 10ng/mL asprosin to induce inflammation, and/or a mixture of SCFAs (2 mM acetate, 0.25 mM butyrate, 0.25 mM propionate). Protein and gene expression of inflammatory markers in the nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) pathway were measured by western blot (n = 6) and RT-qPCR (n = 6).In airway epithelial cells, SCFAs were able to reduce LPS-induced inflammation, through reduction of NFkB gene expression (74%, 12hrs, p < 0.05) and inhibitor of nuclear factor kappa-B kinase subunit beta (IKKb) protein expression (60%, 24hrs, p < 0.001). SCFAs also reduced asprosin-induced inflammation in airway epithelial cells, by reducing NFkB gene (54%, 24hrs, p < 0.05) and protein expression (55%, 12hrs, p < 0.001), IKKb protein expression (49%, 24hrs, p < 0.01), and gene expression of pro-inflammatory interleukin-8 (IL-8; 57%, 12hrs, p < 0.01). Furthermore, SCFAs reduced asprosin gene expression by 72% (12hrs, p < 0.05). In adipocytes, SCFAs were able to reduce NFkB protein expression at 24hrs in cells treated with LPS (61%, p < 0.01) and asprosin (56%, p < 0.05). Although LPS was able to increase the gene expression of NFkB (4.6-fold, p < 0.0001) and IL-8 (63-fold, p < 0.0001) within 6hrs, SCFAs were unable to mitigate this inflammation. SCFAs were however able to reduce NFkB gene expression compared to the control (26%, 12hrs, p < 0.01).These findings suggest that SCFAs have the capacity to mitigate endotoxin and asprosin induced inflammation in airway epithelial and adipocyte cells.
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Bench or experimental | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Bench or experimental | high |
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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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, unvalidatedLabeled directly by 2 models reading the full record.
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".