A311 LEPTIN’S ANOREXIGENIC EFFECTS ARE SWITCHED IN DIET INDUCED OBESITY
Bibliographic record
Abstract
Leptin is well known as a satiety hormone to regulate energy balance by inhibiting hunger. However, an inability for leptin to act normally occurs in obesity, a phenomenon named leptin resistance. Considerable attention has focused on leptin resistance in the hypothalamus. However there has been relatively little attention on vagal afferents, which transmit satiety signals to the CNS. Interestingly, selective knockout of leptin receptor in vagal afferent neurons prevents high fat diet-induced weight gain (de Lartigue, 2014), whereas underlying mechanisms remain unknown. Thus, this study aimed to examine the effects of leptin on satiety signaling via vagal afferents. All experiments were performed on male C57/BL6 mice in accordance with the guideline of Canadian Council for Animal Care. Obese and control mice were fed on a high (HFF, 60% calories from fat) and low (LFF, 10%) fat diet respectively. Membrane excitability of nodose neurons was assessed by whole cell patch clamp. Afferent discharge was recorded from jejunal mesenteric nerves. Incubation of serum from HFF mice overnight resulted in lower excitability of nodose neurons from normal mice compared to LFF mice serum, evidenced by increased rheobase (78.6 ± 16.1 vs. 32.7 ± 5.1 pA, P<0.01, N≥14, unpaired t-test) and reduced number of action potentials at twice rheobase (1.5 ± 0.2 vs. 4.0 ± 0.6 P<0.001, N=14, unpaired t-test). These differences were absent in nodose neurons from leptin receptor deficient mice. Leptin’s inhibitory effect on nodose neuron excitability was blocked by zoledronic acid, an inhibitor of suppressor of cytokine signalling-3 (SOCS3). Effect of leptin on afferent signaling induced by CCK was examined in LFF and HFF mouse jejunum. Co-application of leptin and CCK moderately potentiated afferent response to CCK in LFF mice (P<0.05, one-way ANOVA, N=7), whereas leptin inhibited CCK signaling dose-dependently in HFF mice (P<0.01, one-way ANOVA, N=7). The inhibitory effects of leptin on CCK signaling was blocked by zoledronic acid (P<0.05, Bonferroni test, N=7). These data suggest that leptin’s anorexigenic actions were switched to orexigenic in obesity, and this will provide new strategies for obesity treatment. 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) | 0.004 | 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".