A New Synthetic Analogue of Protectin DX With Enhanced Therapeutic Potential Against Metabolic‐Associated Steatotic Liver Disease
Bibliographic record
Abstract
Obesity, characterized by chronic low-grade inflammation, promotes numerous complications such as type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). A class of lipid mediators known as specialized pro-resolving mediators (SPMs) has garnered interest in this field due to their capacity to promote the resolution of inflammation. One such SPM is Protectin DX (PDX), the stereoisomer of Protectin D1 (PD1). We previously reported that PDX treatment protects against lipid-induced and obesity-linked insulin resistance and attenuates end-stage renal failure in T2D animal models. Our group recently developed a cost-efficient synthesis of PDX and structural analogues to accelerate research on PDX functions and to scale up the production of these molecules to facilitate their pharmaceutical development. After synthesizing and screening over 30 PDX analogues for their bioactivity in relevant cellular models, two analogues, AN-44 and AN-48, were selected for their ability to reduce macrophage inflammation and stimulate muscle glucose uptake in vitro. Since AN-48 also lowers plasma TNF-α in a hamster model of metabolic endotoxemia, it was selected for longer-term in vivo studies. AN-48 (50 ng/g) administered orally daily was found to fully prevent hepatic triglyceride accretion in diet-induced obese hamsters. AN-48 also prevented fasting hyperinsulinemia, insulin resistance, and reduced hepatic inflammation as compared to vehicle or PDX treatments. These results identify AN-48 as a cost-efficient and novel PDX analogue with high therapeutic potential against obesity-linked T2D and MASLD.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".