580-P: Role of Bile Acids in Hepatic Lipid Metabolism: Characterization of the Fasting Lipid and Lipoprotein Profile of Tgr5-/- Hamsters
Bibliographic record
Abstract
Introduction: A major complication of insulin resistant states is fasting dyslipidemia, a lipid profile characterized by elevated triglycerides, increased small dense LDL and low HDL-cholesterol. Recently, bile acid signaling has been suggested to improve hepatic insulin sensitivity and lipid accumulation through activation of the Takeda G protein-coupled receptor 5 (TGR5). Using CRISPR/CAS9 gene editing, and in collaboration with the Wang laboratory at Utah State University, we have developed a novel Tgr5-/- hamster model. As the role of TGR5 in regulating hepatic lipid and lipoprotein metabolism has not been explored, the present study was performed to characterize the fasting lipid profile of this model in normal and mild insulin resistant states and further examine bile acid signaling within these hamsters. Methods/Results: Eight-week-old Tgr5+/+ and Tgr5-/- hamsters were fed a high fat, high fructose and low cholesterol (FFLC) diet for 6 weeks. Glucose tolerance and fasting plasma lipids were examined at baseline, and following 6-weeks of FFLC consumption. Unlike the Tgr5+/+ hamsters, who exhibited impaired glucose tolerance following 6-weeks of FFLC-feeding, Tgr5-/- hamsters did not. This alteration in glucose tolerance was not associated with any significant differences in body weight or food consumption, or hepatic triglyceride or cholesterol between genotypes. Lipoprotein profiling was performed via FPLC analysis. Preliminary results suggest that Tgr5-/- hamsters exhibit reduced VLDL-triglyceride and -cholesterol, and HDL-cholesterol. Finally, chow fed hamsters received intraduodenal injections of deoxycholic acid (DCA), a bile acid with a strong affinity for TGR5. DCA administration was associated with reduced VLDL-triglyceride secretion in Tgr5+/+ hamsters, an effect that was blunted in Tgr5-/- hamsters. The present research will set a framework to expand our knowledge of the role of TGR5 signaling in hepatic lipogenesis. Disclosure D.C.L. Alvares: None. S.S. Hoffman: None. K. Adeli: None. Funding Heart and Stroke Foundation of Canada
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".