Fibroblast growth factor-21 attenuates olanzapine induced hyperglycemia
Bibliographic record
Abstract
Impaired glucose and lipid metabolism are known side effects of the anti-psychotic drug olanzapine. A single bolus of olanzapine induces a rapid rise in blood glucose, circulating fatty acids, and ketones. Strategies to offset these impairments in metabolism are of great interest. Our lab has demonstrated that interventions such as exercise, fasting, and ketogenic diets are effective at reducing olanzapine induced hyperglycemia. Fibroblast growth factor 21 (FGF-21) is a secreted protein that is induced by these interventions. We hypothesized that increased FGF-21 may be a common protective factor in reducing the hyperglycemic response to olanzapine. Our aim was to test if altered FGF-21 concentrations impacted the glycemic response to olanzapine. To increase FGF-21, male mice were fed a low-fat diet (10% Kcal) supplemented with Fenofibrate (0.2% w/w) or a matched control diet for 7 days prior to injection of Olanzapine or vehicle control. The fenofibrate diet significantly increased circulating FGF-21 concentrations (LFD: 744±404pg/ml, Fen: 3187±1050pg/ml, p=0.001, N=14). Olanzapine increased glycemia and circulating fatty acids but mice on the fenofibrate diet had an attenuated glycemic response to olanzapine and reduced circulating fatty acids compared to mice fed the control diet (Area under curve LFD: 1321±354 AU, Fen:1783±70 AU, P=0.0014, N=7). We also investigated if the loss of FGF-21 would lead to an increased glycemic response to olanzapine. In FGF-21 knockout mice, olanzapine induced a larger hyperglycemic response compared to olanzapine treated controls (Area under curve FGF-21 KO: 1788±280 AU, Con:1413±373 AU, p=0.00072, N=12). FGF-21 knockout, however, did not reduce the effect of olanzapine on serum non-esterified fatty acids or beta-hydroxybutyrate. These data show that FGF-21 may determine the extent of the hyperglycemic response to olanzapine and increasing FGF-21 may also offset the impairments in lipid metabolism. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".