A312 INVOLVEMENT OF INOS-DERIVED NO IN THE IMPAIRMENT OF MOUSE VAGAL AFFERENT SENSITIVITY IN DIET-INDUCED OBESITY
Bibliographic record
Abstract
Our previous studies have demonstrated impaired vagal afferent sensitivity to satiety mediators and distention of the gut in high fat fed (HFF) obese mouse iNOS (inducible nitric oxide synthase) knockout mice are protected against high fat diet-induced metabolic dysfunction. In addition, NO has an inhibitory effect on the sensitivity of a select population of vagal afferents. The aim of this study was to examine the involvement of iNOS-derived NO in obesity-induced impairment of vagal nerve sensitivity. All experiments were performed in accordance with the guideline of Canadian Council for Animal Care. Nodose ganglion and jejunum were obtained from high (60% calories from fat) and low (10%) fat fed male C57/BL6 mice. NO was measured using a Nitrate/Nitrite fluorometric assay kit. Membrane excitability of nodose neurons was assessed by whole cell patch clamp. Afferent discharge was recorded from jejunal mesenteric nerves. In comparison with low fat fed (LFF) mice, NO concentration in the jejunum from high fat fed (HFF) mice was significantly increased (P<0.05, N≥7, unpaired t-test) and pre-treatment with L-NIL (10 mg/kg, IP injection) reversed this change (P<0.001, N≥7, unpaired t-test). Excitability of nodose neurons was significantly increased by pre-incubation with L-NIL (10 mM), as evidenced by decreased rheobase (P<0.05, N≥10, unpaired t-test) and increased action potentials at twice rheobase (P<0.05, N≥10, unpaired t-test). In addition, IP injection of L-NIL in HFF mice significantly augmented afferent response to 5-HT (10 mM, P<0.001, N=10, unpaired t-test) and ramp distention (P<0.05, N≥12, two-way ANOVA), while cholecystokinin (CCK, 100 nM) response was partially increased (P=0.09, N≥8, unpaired t-test). In line with this observation, NO donor, sodium nitroprusside (10 mM) inhibited afferent response to 5-HT (P<0.05, N=7, paired t-test) and distention (P<0.001, N=13, two-way ANOVA) instead of CCK in LFF mice. Single unit analysis revealed that NO had diverse effects on the sensitivity of different afferent units. These data suggest that iNOS may be a key molecule in obesity-induced impairment of vagal nerve sensitivity and thus a potential therapeutic target for obesity-related dysfunction. CIHR
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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) | 0.002 | 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".