44-LB: Hypothalamic Glucocorticoid Action Regulates Lipid Metabolism
Bibliographic record
Abstract
Aberrant lipid homeostasis is a feature of diabetes and obesity. This metabolic imbalance is associated with excessive levels and/or actions of glucocorticoids (GCs) and contributes to dyslipidemia including elevated hepatic triglyceride (TG)-rich very low-density lipoprotein (VLDL-TG) secretion. The mediobasal hypothalamus (MBH) is a nutrient and hormone sensing brain region that regulates whole-body lipid metabolism and VLDL-TG secretion. We aimed to assess GC action in the MBH in regulating VLDL-TG secretion in health and diet-induced hyperlipidemia. Sprague Dawley rats received stereotaxic MBH cannulation and vascular catheterizations to enable direct MBH infusions, intravenous injections, and blood sampling. Plasma TG levels and the rate VLDL-TG secretion were measured in 10h-fasted rats following intravenous poloxamer injection with concomitant MBH infusions. In healthy rats, direct MBH GC infusion increased VLDL-TG secretion compared to controls. MBH GC action is mediated via its receptor (GR) since mifepristone (GR antagonist) co-infusion, chronic inhibition of GRs in the MBH with GR shRNA, or inhibition of heat shock protein 90 (required for in vivo GR function) negated the MBH GC-induced increases in VLDL-TG secretion rate. High-fat diet-fed rats had both elevated basal plasma GC levels and hepatic TG secretion compared to healthy rats. Remarkably, chronic MBH GR loss-of-function lowered VLDL-TG secretion in high-fat diet-induced hyperlipidemic rats, independent of changes in body weight. Here, we provide novel in vivo evidence that MBH GC action modulates VLDL-TG secretion and suggest that blocking excessive GC action in the brain improves lipid homeostasis in diet-induced hyperlipidemic rats. These findings may provide insight on lowering lipid levels in diabetes and obesity. Disclosure M. Cardoso: None. M. Wang: None. E. Ling: None. H. Lee: None. E. Beaulieu-Bayne: None. J.T. Yue: None. Funding Diabetes Canada; Natural Sciences and Engineering Research Council of Canada; Canadian Lipoprotein Conference
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".