11β-HSD1 inhibition improves triglyceridemia through reduced liver VLDL secretion and partitions lipids toward oxidative tissues
Bibliographic record
Abstract
Tissue-specific alterations in 11beta-hydroxysteroid dehydrogenase (HSD) type 1 activity, which amplifies glucocorticoid action, are thought to contribute to some of the metabolic complications of obesity. The present study tested whether hypertriglyceridemia is one such complication by investigating the effects of an 11beta-HSD1 inhibitor (compound A, 3 mgxkg(-1)xday(-1), 21 days) on triglyceride (TG) metabolism in a rat model of diet-induced obesity. The dose of compound A used did not affect food intake or final body weight. Compound A improved fasting triglyceridemia (-42%) through a robust reduction (-41%) in hepatic TG secretion rate, without change in plasma TG clearance rate. Uptake of TG-derived fatty acids was, however, increased in oxidative tissues, including red gastrocnemius (+47%), heart (+39%), and brown adipose tissue (BAT, +46%) at the expense of the liver, with a concomitant increase in plasma membrane fatty acid-binding protein. Lipid oxidation products were increased in red gastrocnemius (+35%) and heart (+33%), as were levels of uncoupling protein 1 mRNA in BAT (+48%), and carnitine palmitoyltransferase 1 activity tended to be increased in some oxidative tissues. These findings demonstrate that pharmacological inhibition of 11beta-HSD1 at a dose that does not affect food intake improves triglyceridemia by reducing hepatic very low density lipoprotein-TG secretion, with a shift in the pattern of TG-derived fatty acid uptake toward oxidative tissues, in which lipid accumulation is prevented by increased lipid oxidation.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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 | 0.000 |
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".