Rapid High‐Fat Diet‐Induced Glucose Intolerance is Not Associated with Hepatic Interleukin‐6 Resistance
Bibliographic record
Abstract
Background High‐fat diet (HFD)‐induced hepatic insulin resistance is associated with attenuated hepatic interleukin‐6 (IL‐6) action. This is important as ablation of hepatic IL‐6 signalling worsens systemic glucose tolerance. Hepatic IL‐6 resistance may result from increased content or activity of Src homology phosphatase 2 (SHP2) in the liver, a phosphatase which dephosphorylates STAT3, a downstream IL‐6 signaling intermediate. Objective Determine if the initial development of glucose intolerance with a high fat diet is associated with the onset of liver IL‐6 resistance. Hypothesis HFD will rapidly induce hepatic IL‐6 resistance, in association with impairments in whole body glucose homeostasis and increased liver SHP2 content and activity. Methods C57bl/6 mice (10 per group) had ad libitum access to standard chow or HFD (60% kcal from fat) for 3 d. On the 4 th d, mice were fasted for 6 h before an intraperitoneal (IP) glucose tolerance test. The following day half of the mice in each group were injected IP with IL‐6 (3 ηg kg −1 body weight) or sterile saline. Tissues were harvested 15 min post‐injection. STAT3 phosphorylation and SHP2 activity were assessed via Western blotting. Results Mice fed a HFD were glucose intolerant (P<0.001). This was not associated with attenuated hepatic STAT‐3 phosphorylation following IL‐6 injection. Nor was hepatic SHP2 content or activity increased in HFD mice. Conclusions HFD rapidly causes systemic glucose intolerance but this is not the result of blunted hepatic IL‐6 signalling. Support or Funding Information Ontario Graduate Scholarship and Dairy Farmers of Ontario Doctoral Research Assistantship (LKT) and Natural Sciences and Engineering Research Council and Canada Research Chair (DCW)
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) | 0.003 | 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".