Abstract 58: Adipose-Specific Deletion of ARV1 Results in Decreased HDL Cholesterol, Reduced White Adipose Tissue Mass and Improved Glucose Tolerance in Mice
Bibliographic record
Abstract
ACAT related enzyme 2 required for viability 1 (ARV1) was identified as a gene required for viability in yeast in the absence of cholesterol esterification. ARV1 encodes a putative lipid transporter believed to be important in trafficking of lipids from the ER to the Golgi. ARV1 deficient yeast exhibit profound alterations in cholesterol, phospholipid, and sphingolipid metabolism, accompanied by a constitutively activated unfolded protein response and impaired GPI anchor synthesis. To study the role of ARV1 in mammalian lipid metabolism, we have generated mice with an adipose specific deletion of ARV1 using Cre/loxP technology with Cre expression driven by the Ap2 promoter. ARV1 adipose specific knockout (ASKO) mice exhibited significant reductions in plasma total cholesterol (↓21%, p < 0.05), HDL cholesterol (↓25%, p < 0.01), and phospholipid (↓17.6%, p < 0.05) levels, while fasting triglyceride levels were unaffected. ARV1 ASKO mice also had substantial reductions in epididymal adipose (WT: 0.41 +/- 0.07 g vs. KO: 0.10 +/- 0.07 g, p = 0.0002) and subcutaneous adipose tissue mass (WT: 0.32 +/- 0.03 g vs. KO: 0.11 +/- 0.08 g; p= 0.0002) on a chow diet. In contrast to nearly every other lipodystrophic mouse model, the reduced fat mass in these animals was paradoxically accompanied by improved glucose tolerance (WT AUC: 32,055 vs. KO AUC: 21,470 mg/dl*minutes, p<0.05). These data identify mammalian ARV1 as an important player in adipose tissue biology, and support an important role for adipose tissue in circulating lipoprotein metabolism.
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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 | 0.001 | 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 | 0.000 |
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".