A292 EFFECT OF HIGH FAT DIET ON MECHANOSENSITIVE TRP CHANNEL ACTIVATION IN VAGAL AFFERENT NEURONS
Bibliographic record
Abstract
A number of studies have shown that high fat feeding in the mouse (a commonly used model of diet-induced obesity) results in impaired vagally-mediated satiety responses. Mechanical stimulation of the GI tract is an important stimulus of satiety, and can be mediated by a number of TRP channels (TRPA1, TRPV1 and TRPV4). We sought to examine the effect of chronic high fat diet on responses to TRP channels known to be involved in GI afferent mechanosensation (TRPA1, TRPV1 and TRPV4). C57Bl6J mice were fed a high fat diet (60% kcal from fat-HFF) and controls a low fat diet (10%-LFF). Nodose ganglion neurons were dissociated and Fura 2-AM Ca2+ imaging was performed. In vitro extracellular afferent nerve recordings were performed from segments of jejunum. Responses of TRPA1 (AITC), TRPV1 (capsaicin) and TRPV4 (4αPDD) were examined. High fat diet resulted in a decreased number of neurons responding with increased intracellular Ca2+ to AITC (LFF; 32/72, 44.4% vs. HFF; 26/121, 21.5%, Fisher’s exact test, p<0.01). Reduction in number of neurons responding to 4αPDD did not reach statistical significance (LFF; 40/88, 45.5% vs. HFF; 31/96, 32.3% p=0.07) and there was minimal change in proportion of neurons responding to capsaicin. Consistent with this, magnitude of the Ca2+ increase induced by AITC (LFF-3.77 ± 0.43 n=19 and HFF 2.36 ± 0.33 n=20 p<0.05) and 4αPDD (LFF-2.64 ± 0.43 n=18, and HFF 1.47 ± 0.26 n=16) was reduced in HFF neurons with no change in the capsaicin response. In jejunal afferent recordings We saw a significant reduction in the afferent response to 4αPDD (p<0.01) and AITC (p<0.05), but not capsaicin. Our results have shown decreased responses to the mechanosensitive TRP channels TRPA1 and TRPV4 at the vagal afferent cellular level as well as at the level of the nerve terminal in the intestine. The response to TRPV channel activation seems to be preserved. These results may explain some of the reduced sensitivity of GI vagal afferents to mechanical stimuli and may lead to decreased meal-induced satiety signals. CIHR
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) | 0.000 | 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) | 0.004 | 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".