134-OR: NOD1 Deletion in Skeletal Muscle Protects against Palmitate-Induced Insulin Resistance
Bibliographic record
Abstract
Introduction and Objective: Nucleotide-binding oligomerization domain 1 (Nod1), an immune receptor, drives fat-induced insulin resistance. Recent studies show that whole-body and hematopoietic Nod1 knockout (KO) protect against insulin resistance. However, it remains uncertain whether the effect in whole-body KO is due to Nod1 deficiency in macrophages or in extra-macrophage cell(s). Nod1 is expressed in insulin-sensitive tissues, with evidence showing fatty acids activate Nod1 in adipocytes and Nod1 activators induce insulin resistance in hepatocytes, suggesting a potential role for extra-macrophage Nod1. To investigate the tissue-specific effects of Nod1, fat infusions were conducted in muscle-specific KO mice, as skeletal muscle is a primary site for insulin regulated glucose metabolism and whole-body Nod1KO mice are protected against peripheral insulin resistance. Methods: We have generated skeletal muscle specific Nod1KO mice by crossing Nod1 floxed mice with Myf6Cre+ mice. Both wild-type (WT, i.e. Nod1 f/f and Myf6Cre+) and KO mice underwent a 48-hour infusion with ethylpalmitate, which is hydrolyzed in plasma into palmitate and ethanol to elevate circulating free fatty acids (FFA) in a non-toxic manner. After the infusion, we performed a hyperinsulinemic-euglycemic clamp to evaluate insulin sensitivity. A radioactive tracer (3-H3) was also used to differentiate hepatic from peripheral insulin resistance. Results: Nod1 deficiency in skeletal muscle alleviated palmitate-induced insulin resistance observed in WT mice. Tracer analysis showed that muscle Nod1KO significantly increased insulin-stimulated glucose utilization, however had no effect on hepatic glucose production. Conclusion: Our findings suggest that skeletal muscle-specific Nod1 deletion protects against palmitate-induced insulin resistance by enhancing peripheral insulin sensitivity. This highlights the critical role of muscle Nod1 in regulating insulin action and glucose metabolism. Disclosure S. Rahman: None. K. Sun: None. J. Park: None. M.A. Garcia: None. A. Giacca: None. Funding Canadian Institutes of Health Research (CIHR 507485)
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 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".